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August 25, 2014
Austrianova released results of a phase II
study of Cell-in-a-Box combined with ifosfamide
for treatment of advanced, inoperable
cancer. Thirteen patients with advanced, inoperable
pancreatic cancer have been treated
with the Cell-in-a-Box/ifosfamide combination
in the uncontrolled (no comparator arms),
open-label study. A single implantation of
Cell-in-Box capsules (each capsule contained
approximately 10,000 cells capable of converting
the anticancer prodrug ifosfamide into its
“cancer-killing” form by virtue of their overexpression
of an isoform [CYP2B1] of human
cytochrome P450) was used and two courses
of treatment with ifosfamide were administered.
There were no deleterious effects, such
as inflammation or pancreatitis, that could be
attributed to the Cell-in-a-Box capsules being
implanted in the patients. The median survival
of patients in the phase I/II clinical trial was
about 40 weeks versus the 33 weeks seen in
the phase II clinical trial. The percentage of
patients who survived one year was somewhat
lower in the phase II clinical trial (23%) than in
the phase I/II clinical trial (38%). The dose (1g/
m2) of ifosfamide used in the phase I/II clinical
trial was one-third of the “normal” dose of
ifosfamide, whereas the dose used in the phase
II clinical trial was twice (2g/m2) that dose. A
phase IIb trial has been planned in Australia
implementing the 1g/m2 dose of ifosfamide
instead of the 2g/m2 dose.
August 11, 2014
Amgen and Onyx Pharmaceuticals
reported results of a phase III study of Kyprolis (carfilzomib) for injection in combination with Revlimid (lenalidomide) and low-dose dexamethasone (KRd) for multiple myeloma. Patients were randomized to receive Kyprolis (20mg/m on days one and two of cycle one only, then 27mg/m subsequently), in addition to a standard dosing schedule of lenalidomide (25mg per day for 21 days on, seven days off) and low-dose dexamethasone (40mg per week in four week cycles), versus lenalidomide
and low-dose dexamethasone alone. The study randomized 792 patients at sites in North America, Europe and Israel. Patients treated with Kyprolis for injection in combination
with Revlimid and low-dose dexamethasone
lived significantly longer without their disease worsening (median 26.3 months) compared to patients treated with Revlimid and low-dose dexamethasone (Rd) (median 17.6 months) (HR=0.690, 95% CI, 0.570, 0.834, p<0.0001). Treatment discontinuation due to adverse events and on-study deaths were comparable between the two arms. These results will form the basis for regulatory submissions
throughout the world beginning in the first half of 2015.
August 4, 2014
Celsion released result of an ongoing, open-label
phase II trial of ThermoDox in recurrent
chest wall breast cancer (RCWBC). The trial is
designed to enroll 20 patients at several U.S.
clinical sites and is evaluating ThermoDox in
combination with mild hyperthermia. Of the 13
patients enrolled and treated, 10 were eligible
for evaluation of efficacy. To date, 60% of patients
experienced a stabilization of their highly
refractory disease with a local response rate
of 50% observed in the 10 evaluable patients,
notably three complete responses, two partial
responses and one patient with stable disease.
July 14, 2014
Taiho Oncology issued results of a
phase III trial of TAS-102 (trifluridine
and tipiracil hydrochloride) for the treatment
of refractory metastatic colorectal
cancer. The trial was a global, randomized,
double-blind, placebo-controlled comparison
trial. The trial enrolled 800 patients in
North America, Japan, Europe and Australia
who received at least two prior regimens
of standard chemotherapies for mCRC and
were refractory to, or failed, those chemotherapies.
Patients were randomized (2:1)
to receive TAS-102 (35mg/m2) or placebo,
plus best supportive care, twice daily.
The trial met the primary efficacy endpoint
of statistically significant improvement in
overall survival versus placebo (H =0.68,
p<0.0001). TAS-102 reduced the risk of
mortality by 32% when compared to
placebo. Median overall survival was 7.1
months (95% CI: 6.5-7.8) and 5.3 months
(95% CI: 4.6-6.0) for TAS-102 and placebo,
respectively, and was improved in favor
of TAS-102 by 1.8 months. There also was
a statistically significant 52% decrease in
the risk of disease progression between
the two arms (HR=0.48, p<0.0001). In
addition, the disease control rate of
patients treated with TAS-102 was 44.0%
versus 16.3% for patients treated with
placebo (p<0.0001). Taiho plans to submit
regulatory submissions in the U.S. at the
end of 2014 and in Europe in the first
quarter of 2015.
June 23, 2014
Novartis reported phase I trial results
of Zykadia (LDK378) in patients with
anaplastic lymphoma kinase-positive (ALK+)
non-small cell lung cancer (NSCLC). The 246
patients with ALK+ NSCLC in this single-arm
study received ceritinib 750mg ALK+ daily.
Findings from the study showed patients
treated with ceritinib achieved an ORR of
58.5% [95% CI, 52.1-64.8%] and a median
PFS of 8.2 months [95% CI, 6.7-10.1 months].
The median duration of response was 9.7
months [95% CI, 7.0-11.4 months], with a
median time to first response of six weeks
after starting treatment. Among 163 patients
receiving 750 mg of ceritinib daily and who
were previously treated with the commonly
prescribed ALK inhibitor crizotinib, ORR
was 54.6% [95% CI, 46.6-62.4%] and PFS
was 6.9 months [95% CI, 5.4-8.4 months].
In 83 patients who had not received prior
treatment with an ALK inhibitor, ORR was
66.3% [95% CI, 55.1-76.3%] and PFS had
not been reached. In the 124 patients who
started the study with brain metastases,
ceritinib achieved an ORR of 54.0% [95% CI,
44.9-63.0%] and a median PFS of 6.9 months
[95% CI, 5.4-8.4 months]. Tumor shrinkage
was seen in 50.0% of patients [49 of
98 patients; 95% CI, 39.7-60.3%] with brain
metastases who had received previous ALK
inhibitor therapy, while 69.2% of patients
[18 of 26 patients; 95% CI, 48.2-85.7%] with
brain metastases who were not previously
treated achieved tumor shrinkage following
treatment with ceritinib.
June 2, 2014
Boehringer Ingelheim reported result
of two phase III trials (LUX-Lung 3 and
LUX-Lung 6) of afatinib for treatment
of advanced non-small cell lung cancer
(NSCLC) with epidermal growth factor
receptor (EGFR) mutation. The LUX-Lung 3
trial compared afatinib with chemotherapy
(pemetrexed/cisplatin); LUX-Lung 6
evaluated afatinib v. chemotherapy
(gemcitabine/cisplatin) for Asian patients.
Afatinib prolonged survival of lung cancer
patients whose tumors have common
EGFR mutations compared with standard
chemotherapy by a median of three months
(27.3 to 24.3 months) and significantly
reduced the risk of death by 19% (HR=0.81,
p=0.037). The most pronounced reduction
in risk of death was 41% (HR=0.59, CI 0.45,
0.77) in patients whose tumors have the
most common EGFR mutation (exon 19
deletion of the EGFR gene); for patients
with the exon 21 (L8585R) mutation
there was no impact on overall survival
(HR=1.25, CI 0.92, 1.71). Those patients
who continued afatinib treatment, with
the addition of chemotherapy, after
progressing on afatinib alone, had a further
delay in tumor growth compared to the
group who stopped afatinib treatment
and received chemotherapy only (tumor
growth was delayed by 5.6 months and
2.8 months respectively, p=0.003). This
corresponded to a 40% reduction in risk of
disease progression (HR=0.60). The most
common adverse events in patients treated
with afatinib and chemotherapy versus
chemotherapy were diarrhea (53.8% v.
6.7%), hair loss or alopecia (32.6% v. 15%)
and weakness or asthenia (27.3% v. 28.3%).
April 28, 2014
GlaxoSmithKline and Genmab released
results of a phase III study of Arzerra (ofatumumab),
in combination with chlorambucil
for previously untreated patients with chronic
lymphocytic leukemia (CLL). Results from the
randomized, open-label, parallel-arm, pivotal
phase III study evaluating the combination
of ofatumumab and chlorambucil (N=221) v.
chlorambucil alone (N=226) demonstrated
statistically significant improvement in median
PFS in patients randomized to ofatumumab
and chlorambucil compared to patients randomized
to chlorambucil alone (22.4 months
v. 13.1 months, respectively) (HR=0.57 [95%
CI, 0.45, 0.72] <0.001). The majority of adverse
reactions (ARs) were Grade 2 or lower in both
treatment arms. The most common (>/=5% in
the ofatumumab plus chlorambucil arm and
also >/=2% more than in the chlorambucil
monotherapy arm) non-infusion-related ARs
(all grades) as reported by investigators within
60 days following the last treatment were
neutropaenia (27% ofatumumab + chlorambucil,
18% chlorambucil), asthaenia (8%, 5%),
headache (7%, 3%), leukopaenia (6%, 2%),
herpes simplex (6%, 4%), lower respiratory tract
infection (5%, 3%), arthralgia (5%, 3%) and upper
abdominal pain (5%, 3%).
April 14, 2014
Synta Pharmaceuticals issued interim
results from a single-arm, multi-center, phase
II proof-of-concept study designed to evaluate
ganetespib for the treatment of metastatic
breast cancer. Target enrollment is 35 patients
in three cohorts, which include HER2+ breast
cancer, triple-negative breast cancer (TNBC)
and, recently added and now recruiting,
ER/PR-positive patients previously untreated
for locally advanced or metastatic disease.
The goal of the trial design is to obtain initial
evidence of a clinical activity signal with
single-agent ganetespib administered for
up to 12 weeks. Ten patients were enrolled
into the HER2+ cohort and 38 patients were
enrolled into the TNBC cohort. Of the patients
evaluable for metabolic response based on
having reached the week 3 PET assessment,
six of seven achieved a metabolic response
in the HER2+ cohort and 18 of 31 achieved
a metabolic response in the TNBC cohort.
Of the 6 HER2+ and 26 TNBC patients that
reached the six-week assessment and therefore
evaluable for objective RECIST response, four
achieved an objective response and two
achieved stable disease in the HER2+ cohort,
while two achieved an objective response, 11
achieved stable disease and 13 had progressive
disease in the TNBC cohort. One HER2+ patient
achieved a complete objective response and
has remained on treatment for over 10 months.
April 7, 2014
Novartis released results of a phase I
study of LDK378 in 130 patients for the
treatment of advanced anaplastic lymphoma
kinase positive (ALK+) non-small cell
lung cancer (NSCLC). Of 114 ALK+ NSCLC
patients treated with LDK378 at 400mg or
higher per day, 80 had progressed during
or following treatment with crizotinib,
and 34 patients with ALK+ NSCLC were
crizotinib-naive. The maximum tolerated
dose observed in the study was 750mg
per day. The median duration of response
for the 66 responding patients treated at
400mg or higher per day was 8.2 months
[95% CI; 6.9-11.4 months]. In all, 114 ALK+
NSCLC patients treated at 400mg or higher
per day, median progression-free survival
was 7 months [95% CI; 5.6-9.5 months]. In
the 114 ALK+ NSCLC patients treated with
LDK378 at 400mg or higher per day, the
overall response rate (ORR) was 58% [95%
CI; 48-67%] (1 complete response [CR] and
65 partial responses [PR]), which includes
those patients who had progressed during
or after crizotinib therapy (ORR 56% [95%
CI; 45-67%]) and those who were crizotinibnaive
(ORR 62% [95% CI; 44-78%]). In the
78 patients with ALK+ NSCLC who received
LDK378 at the maximum tolerated dose of
750mg per day, the ORR was 59% [95% CI;
47-70%] (46 PRs), which includes those who
had progressed during or after crizotinib
therapy (ORR 56% [95% CI; 41-70%]) and
those who were crizotinib-naive (ORR
64% [95% CI; 44-81%]). The most frequent
adverse events were nausea (82%), diarrhea
(75%), vomiting (65%), fatigue (47%) and
increased alanine aminotransferase levels
(35%). At the 750mg dose level, 50 of 81
patients (62%) required at least one dose reduction,
of which 32 occurred in cycle three
or later. The FDA has accepted regulatory
filings for LDK378.
March 24, 2014
Amgen issued results of a phase III study of
talimogene laherparepvec in patients with
injectable unresected stage IIIB, IIIC or IV melanoma
compared to granulocyte-macrophage
colony-stimulating factor (GM-CSF). Of the
295 patients treated with talimogene laherparepvec,
almost 4,000 tumor lesions were
tracked. Half of these lesions were injected
with talimogene laherparepvec at least once,
while the rest were not injected, including
visceral tumor lesions. The results showed
a 50% or greater reduction in tumor size in
64% of injected tumors. In addition, one-third
of uninjected non-visceral tumors, and 15%
of visceral tumors, also were reduced by at
least 50%. There were 35 melanoma-related
surgeries performed during this trial, of which
30% successfully removed all residual disease.
The most frequently observed adverse events
in the phase III study were fatigue, chills and
pyrexia. The most common serious adverse
events include disease progression in both
groups, and cellulitis and pyrexia in the talimogene
March 3, 2014
Eli Lilly reported results of a phase III study of
ramucirumab in combination with chemotherapy
in patients with second-line non-small cell
lung cancer (NSCLC). The global, randomized,
double-blind trial compared ramucirumab and
docetaxel to placebo and docetaxel in NSCLC
patients whose disease has progressed after
failure of prior platinum-based chemotherapy
for locally advanced or metastatic disease.
Ramucirumab showed a statistically significant
improvement in overall survival in the
ramucirumab-plus-docetaxel arm compared
to the control arm of placebo plus docetaxel,
and a statistically significant improvement in
progression-free survival in the ramucirumab
arm compared to the control arm. The most
common (>5% incidence) Grade 3 adverse
events on the ramucirumab-plus-docetaxel
arm were decreased white blood cell count
(neutropenia/leukopenia), febrile neutropenia,
fatigue/asthenia and hypertension.
February 17, 2014
Aeterna Zentaris reported results of a
phase II trial of zoptarelin doxorubicin
(AEZS-108) for the treatment of endometrial
cancer. Forty-four patients entered into
the study at eight centers in Germany and
three centers in Bulgaria. Forty-three of
these patients were eligible. Two patients
had a complete remission (5%) and eight
achieved a partial remission (18%). Stable
disease for at least six weeks was observed
in 44%. The median time to progression
(TTP) was seven months and median overall
survival (OS) was 15 months. The most
frequently reported grade 3 or 4 adverse effects
were neutropenia (12%) and leucopenia
(9%). Data showed zoptarelin doxorubicin
has clinically meaningful activity with
low toxicity in women with advanced or recurrent
LHRH receptor positive endometrial
cancer, supporting the principle of receptor
mediated targeted chemotherapy. These
results were the basis of a phase III trial of
zoptarelin doxorubicin, currently enrolling.
Eisai reported positive results of a phase
III trial of lenvatinib for the treatment
of radioiodine-refractory differentiated
thyroid cancer (RR-DTC). The study was a
multicenter, randomized, double-blind,
placebo-controlled, phase III study to compare
the PFS of patients with radioiodinerefractory
differentiated thyroid cancer and
radiographic evidence of disease progression
within the prior 12 months, treated
with once-daily, oral lenvatinib (24mg) v.
placebo. Secondary endpoints of the study
included overall response rate (ORR), overall
survival (OS) and safety. The study enrolled
392 patients at over 100 sites in Europe,
North and South America and Asia. The
preliminary safety analyses showed the
five most common adverse reactions were
hypertension, diarrhea, decreased appetite,
decreased weight and nausea. Based on
positive clinical results, Eisai will submit
marketing authorization applications for
lenvatinib to health authorities in the U.S.,
Japan and Europe.
Medivation and Astellas Pharma
released results of a phase III trial of
enzalutamide in patients with chemotherapy-
naïve metastatic prostate cancer who
have failed androgen deprivation therapy
and have few or no symptoms. The trial
is a randomized, double-blind, placebocontrolled,
multi-national trial that enrolled
more than 1,700 patients at sites in the U.S.,
Canada, Europe, Australia, Russia, Israel and
Asian countries including Japan. The trial
was designed to evaluate enzalutamide at
a dose of 160mg taken orally once daily v.
placebo. Treatment with enzalutamide demonstrated
a statistically significant overall
survival benefit compared with placebo
treatment. Enzalutamide reduced the risk
of death by 29% (HR=0.71). Treatment with
enzalutamide significantly reduced the
risk of radiographic progression or death
by 81% compared with placebo treatment
(HR=0.19). Men taking enzalutamide
experienced a 17-month delay in the time to
initiation of chemotherapy compared with
men taking placebo (28.0 months versus
10.8 months; HR=0.35). Enzalutamide extended
the median time to PSA progression
from 2.8 months (placebo) to 11.2 months
(HR= 0.169). Nearly four out of five patients
in the enzalutamide group experienced a
PSA decline of 50% or more, compared to
less than 4% in the placebo group (78% vs.
3.5%). Regulatory applications to the FDA
will be filed in early 2014.
February 10, 2014
Pfizer issued results of a phase II trial of
palbociclib for the treatment of human
epidermal growth factor receptor 2 negative
(HER2-) locally advanced or newly diagnosed
metastatic breast cancer. The phase
II, multi-center trial, with 101 global sites
participating, was designed to assess the
PFS of palbociclib (125mg once daily for
three out of four weeks in repeated cycles)
in combination with letrozole v. letrozole
alone (2.5mg once daily on a continuous
regimen) in post-menopausal women with
ER+, HER2- advanced breast cancer. PFS is
comprised of time from randomization to
time of disease progression or death from
any cause. A randomized, global phase III
trial (PALOMA-2) in this patient population is
currently enrolling patients.
January 6, 2014
Takeda Pharmaceutical issued results of a phase III study of VELCADE (bortezomib) for the treatment of multiple myeloma (MM) in previously untreated patients. Results showed a higher cumulative dose suggests improved overall survival (OS) (hazard ratio [HR] 0.53; p<0.0001). Patients who received a cumulative dose of VELCADE of 39mg/m2 or greater lived 20 months longer on average than those who received lower cumulative doses (median OS 66.3 months and 46.2 months, respectively). Patients (n=340) treated with the VELCADE-melphalan-prednisone regimen received up to nine six-week cycles (up to 54 weeks) of the combination therapy (cycles 1-4: VELCADE 1.3mg/m2 IV, days 1, 4, 8, 11, 22, 25, 29, 32; cycles 5-9: VELCADE 1.3mg/m2 IV, days 1, 8, 22, 29; all cycles: melphalan 9mg/m2 and prednisone 60 mg/m2). The maximum planned dose of VELCADE was 67.6mg/m2, including 41.6mg/m2 during cycles 1-4 and 26mg/m2 during cycles 5-9. The median cumulative VELCADE dose received was 39mg/m2. OS was longer in patients in the higher (=39 mg/m2) v. lower (<39 mg/m2) cumulative dose group (median 66.3 v. 46.2 months; HR 0.53; p<0.0001). The HR for OS between the two groups, adjusted for age differences, that were significant between the two groups, was 0.56 (p=0.0002). A landmark analysis showed that in patients who survived past the 180-day threshold, OS was longer in the higher (=39mg/m2) v. lower (<39mg/m2) cumulative dose group (median 60.4 v. 50.3 months; HR 0.71; p=0.04).
December 9, 2013
Oncolytics Biotech reported results of
Reolysin in combination with carboplatin
and paclitaxel in patients with second-line
platinum-refractory, taxane-naïve head
and neck cancers. The double-blinded,
randomized study enrolled 167 patients and
showed a median PFS of 94 days in the test
arm (n=62), v. 50 days in the control arm
(n=56). Patients were evaluated for progression
at the first scheduled post-treatment
scan (performed at six weeks, post-cycle
two of therapy). Of 62 patients on the test
arm, 32.3% had progressed, compared with
51.8% of the 56 patients on the control arm
(p=0.04). Of 86 patients with measurable
disease at the first post-treatment scan, the
test arm (n=48) had a statistically significant
increase in tumor shrinkage over the control
arm (n= 38; p=0.049).
Threshold Pharmaceuticals issued results
of a phase I trial of TH-302 in combination
with Avastin (bevacizumab) in patients with
recurrent glioblastoma following bevacizumab
failure. No dose-limiting toxicity has
been reported to date at doses of TH-302 up
to 670mg/m2 plus bevacizumab at 10mg/m2
every two weeks. A total of 19 patients have
been enrolled in the ongoing trial. Of 14
patients evaluable for tumor response, the
median time to progression was 86 days.
46% (95% CI: 18%-74%) of patients were
alive without disease progression after three
months of treatment. Preliminary data in 14
patients showed TH-302 in combination with
bevacizumab was associated with a median
time to progression of 2.8 months. One patient
achieved a complete response and two
patients achieved partial responses. No grade
4 adverse events were observed at any dose.
Two grade 3 adverse events were observed at
340mg/m2 and 670mg/m2 of skin ulceration
and thrombocytopenia, respectively. The
study is continuing to enroll patients.
December 2, 2013
Merck issued results for a phase Ib trial of
MK-3475 for the treatment of advanced
melanoma. The trial is an ongoing, multi-center,
single-arm, open-label study evaluating
MK-3475 monotherapy in more than 1,000
patients with diverse late-stage cancers
lung and melanoma. Three dosing regimens
of MK-3475 were evaluated: 10mg/kg every
two weeks, 10mg/kg every three weeks or
2mg/kg every three weeks. The overall
response rate at five months was 41%
(CI 95%: 32 to 51%); 88% (43/49) of patients
with a partial or complete response showed
no evidence of disease progression. The
maximum ongoing duration of response
recorded was 65 weeks (range 8+ to 65+).
The disease control rate across doses for
patients in the melanoma cohort was 61%
(CI 95%: 52 to 70%), and median progressionfree
survival at time of analysis was 36 weeks.
The company plans to initiate combination
trials this year and in early 2014.
November 18, 2013
Angiochem released results of a phase II
study of ANG1005 in 80 HER2-positive and
HER2-negative breast cancer patients with
brain metastases. Two doses, 650mg/m2
(n=13) and 550mg/m2 (n=67), were evaluated
for intracranial anti-tumor responses
including response rate, progression-free survival
(PFS) and overall survival (OS). ANG1005
adverse events included neutropenia,
fatigue, peripheral neuropathy and mucosal
inflammation. HER2-positive patients (n=36)
achieved PR’s (9, 25%) and stable disease
(SD) (18, 50%) thereby demonstrating
disease control in 75% of those patients. At
550mg/m2, three month PFS was 71% with a
median PFS of 128 days and OS at six months
of 82%. Her2-negative patients (n=44)
achieved PR’s (5, 11%) and SD (17, 32%),
demonstrating disease control in 50% of
patients. In addition, at 550mg/m2, three
months of PFS was 35% with a median PFS
of 84 days and OS at six months of 60%.
Angiochem will advance ANG1005 into a
phase II clinical study in patients with
recurrent high grade gliomas and a phase II
clinical study in HER2-positive breast cancer
patients with brain metastases.
November 11, 2013
Medivation and Astellas Pharma reported results of a phase III trial of enzalutamide in 1,700 men with metastatic prostate cancer that has progressed despite androgen deprivation therapy and who have not yet received chemotherapy. The randomized, double-blind, placebo-controlled, multinational trial enrolled patients at sites in the U.S., Canada, Europe, Australia, Russia, Israel and Asian countries including Japan. The trial was designed to evaluate enzalutamide at a dose of 160mg taken orally once daily v. placebo. Patients treated with enzalutamide demonstrated a statistically significant overall survival advantage compared with patients receiving placebo (p<0.0001). Enzalutamide provided a 30% reduction in risk of death compared with placebo (Hazard Ratio=0.70; 95% confidence interval, 0.59- 0.83). Patients treated with enzalutamide demonstrated a statistically significant radiographic progression-free survival advantage compared with placebo (p<0.0001). Enzalutamide provided an 81% reduction in risk of radiographic progression or death compared with placebo (Hazard Ratio=0.19; 95% confidence interval, 0.15-0.23). The percentage of patients alive in the enzalutamide arm was 72%, as compared with 65% in the placebo arm, at the time of the interim analysis data cut-off date. Treatment with enzalutamide resulted in a calculated point estimate for median overall survival of 32.4 months (95% confidence interval, 31.5 months-upper limit not yet reached) v. 30.2 months (95% confidence interval, 28.0 months-upper limit not yet reached) for patients receiving placebo. Medivation and Astellas will initiate meetings with and submissions to regulatory agencies beginning in early 2014.
October 28, 2013
Acacia Pharma issued results from a phase II study of APD515 for the treatment of xerostomia (dry mouth) in advanced cancer patients. The randomized, double-blind, placebo-controlled, cross-over trial was conducted in 11 centers in the U.K. and Denmark, and enrolled 32 patients with advanced cancer and a persistently dry mouth. Patients received a week of APD515 treatment and a week of placebo, in a randomly assigned order, with a week’s washout in between. Patients graded their symptoms before and after treatment and were asked to record which treatment week they preferred. Patients’ unstimulated salivary flow was measured before and after each treatment period. Subjective scoring was done on a standard 100mm visual analogue scale, where 0 represented no dryness and 100 the worst dryness possible. The average score for mouth dryness was 26.01 after treatment with APD515 and 43.52 after placebo (p=0.0005). Other subjective scores, for oral comfort, difficulty speaking and difficulty swallowing, all showed a significant improvement for APD515 over placebo. The overall number of adverse events was low, with no significant difference between APD515 and placebo.
September 9, 2013
Incyte issued results of a phase II trial of ruxolitinib, its oral JAK1 and JAK2 inhibitor, in combination with capecitabine in patients with recurrent or treatment refractory metastatic pancreatic cancer. The randomized, double-blind, placebo-controlled trial enrolled 136 patients. The hazard ratio (HR) for overall survival (OS) in the intent to treat population was 0.79 (one-sided p=0.12), and in a pre-specified subgroup analysis conducted in patients identified prospectively as most likely to benefit from JAK pathway inhibition, the HR for OS was 0.47 (one-sided p=0.005). Within this subgroup of patients, which represented 50% of the randomized population, six-month survival in the ruxolitinib arm was 42% v. 11% for placebo. Durable tumor responses were observed only in patients receiving ruxolitinib, and ruxolitinib-treated patients achieved a significant improvement in body weight relative to placebo. A phase III trial will be reviewed with the FDA.
August 19, 2013
Boehringer Ingelheim issued results of a phase III study of afatinib in patients with advanced non-small cell lung cancer (NSCLC). Data from the LUX-Lung 3 trial demonstrate superiority of afatinib over chemotherapy considered best-in-class (pemetrexed/cisplatin) in EGFR-mutation positive advanced NSCLC patients. Patients treated with afatinib lived for almost one year (progression-free survival (PFS) of 11.1 months) before their tumor started to grow again compared to just over half a year (PFS of 6.9 months) for those treated with chemotherapy. Patients taking afatinib with the most common EGFR mutations (del19 and L858R, accounting for 90% of all EGFR mutations) lived for well over a year without progression (PFS of 13.6 months) v. just over half a year (PFS of 6.9 months) for those in the comparator arm. Afatinib significantly delayed the time to deterioration for cough (hazard ratio [HR], 0.60; P=0.007) and dyspnoea (HR, 0.68; P=0.015) and showed significantly better mean scores over time in global health status/QoL (P=0 .015) and physical (P<0.001), role (P=0.004) and cognitive (P=0.007) functioning compared with chemotherapy, as measured by standard questionnaires. The LUX-Lung clinical trial program currently involves eight studies designed to investigate the use of afatinib in various settings of advanced NSCLC, including head-to-head trials with the first-wave of reversible tyrosine kinase inhibitors.
August 12, 2013
GlaxoSmithKline issued results of a randomized, double-blind, phase III, placebo controlled trial of pazopanib monotherapy in women with epithelial ovarian, fallopian tube or primary peritoneal cancer whose disease had not progressed after completing standard debulking surgery and first-line chemotherapy. After completion of five or more cycles of platinum-taxane chemotherapy, 940 patients were randomized 1:1 to receive 800mg pazopanib once daily or placebo for up to 24 months (median time from diagnosis to randomization was approximately seven months). Pazopanib treatment reduced the risk of disease progression or death by 23% (HR = 0.77; 95% CI: 0.64-0.91; p = 0.0021). The incidence of serious adverse events was higher in the pazopanib group compared to the placebo group (26% v. 11%). Regulatory applications will be submitted before 2014.
Immunomedics reported results of a phase Ib study of 90Y-labeled-clivatuzumab for the treatment of metastatic pancreatic cancer in 58 patients who had received at least two prior treatments. Patients were randomized to receive either 90Y-labeled-clivatuzumab once a week for three weeks at 6.5mCi/m2 with gemcitabine 200mg/m2 given weekly for four weeks (Arm A) or 90Y-labeled-clivatuzumab alone (Arm B). This treatment cycle was repeated every four weeks until unacceptable toxicity, patient deterioration or patient withdrawal. Patients were followed for one year or until death. The median overall survival (OS) for Arm A (N=27) was 119 days, an improvement over Arm B (N=26), with a median OS of 80 days (P=0.04). For the 23 patients who received multiple cycles of therapy, the median OS increased to 157 days in Arm A compared with 103 days in Arm B. Survival also was related to patients’ Karnofsky Performance Status (KPS) scores at study entry, increasing from a median of 79 days for patients with 80% KPS to 119 days for patients with 90% to 100% KPS. In contrast, increased number of prior treatments is a negative prognostic indicator for survival. The median OS decreased from 90 to 82 to 73 days for patients who received 2, 3 or 4 to 5 prior treatments, respectively. Phase III trials are planned for 2013 or the beginning of 2014 in the U.S. and the E.U.
July 29, 2013
Amgen released results from a phase II study of XGEVA (denosumab) in adults and skeletally mature adolescents diagnosed with giant cell tumor of bone (GCTB). In the international, open-label, phase II study enrolling 282 patients, there were three cohorts: patients with surgically unsalvageable GCTB (Cohort 1), patients with salvageable GCTB whose surgery was associated with severe morbidity (Cohort 2) and patients who transferred from a previous XGEVA GCTB study (Cohort 3). All three cohorts received subcutaneous XGEVA 120mg every four weeks with loading doses on days eight and 15. In Cohort 1, 96% (163/169) of patients had no disease progression after a median follow-up of 13 months. In Cohort 2, 74% (74/100) of patients required no surgery and 62% (16/26) of patients who had surgery underwent a less morbid procedure than planned. XGEVA was approved June 13 by the FDA for the treatment of adults and skeletally mature adolescents with GCTB that is unresectable or where surgical resection is likely to result in severe morbidity.
Bayer HealthCare issued results from a phase III study of Xofigo in castration-resistant prostate cancer (CRPC) patients with symptomatic bone metastases. The randomized, double-blind, placebo-controlled, international study enrolled 921 patients in 100 centers in 19 countries. Patients were stratified based on their baseline alkaline phosphatase (ALP) level, current bisphosphonate use and whether or not they had received docetaxel prior to enrollment. Treatment consisted of up to six intravenous injections separated by four weeks. Xofigo improved overall survival (OS) at the prespecified interim analysis (HR=0.695, [95% CI: 0.552-0.875], p=0.00185); median OS was 14.0 months with Xofigo (95% CI: 12.1-15.8) vs. 11.2 months with placebo (95% CI: 9.0-13.2). These findings were supported by an exploratory analysis performed before patient crossover with an additional 214 events in which Xofigo showed improvement in OS (HR=0.695, [95% CI: 0.581-0.832]); median OS was 14.9 months in the Xofigo arm (95% CI: 13.9-16.1) v. 11.3 months in the placebo arm (95% CI: 10.4-12.8). These data supported the FDA approval of Xofigo injection in May.
July 1, 2013
Amgen reported results from a phase III trial of trebananib plus paclitaxel v. placebo plus paclitaxel for the treatment of recurrent ovarian cancer. This global, multicenter, randomized, double-blind, placebo-controlled study enrolled 900 women with recurrent partially platinum-sensitive or -resistant (platinum-free interval of 12 months or less) epithelial ovarian, primary peritoneal or fallopian tube cancer. Patients were randomized 1:1 to receive either 15mg/kg of intravenous trebananib weekly plus 80mg/m of intravenous paclitaxel weekly (three weeks on, one week off) or weekly intravenous placebo plus 80mg/m of intravenous paclitaxel weekly (three weeks on, one week off). The trial met its primary endpoint of progression-free survival (PFS). A statistically significant difference was observed in PFS with a 34% reduction in the risk of disease progression or death (HR = 0.66, 95% CI, 0.57, 0.77, p<0.001). The median PFS was 7.2 months in the trebananib arm v. 5.4 months in the control arm.
June 24, 2013
Novartis reported results from a phase I trial of LDK378 for anaplastic lymphoma kinase positive (ALK+) metastatic non-small cell lung cancer (NSCLC) in patients who had progressed during or after crizotinib therapy or had not been previously treated with crizotinib. This single-arm study enrolled 114 patients. The results showed an overall response rate of 60% in patients with ALK+ NSCLC taking LDK378 (750 mg/day), which includes patients who had progressed during or after crizotinib therapy (overall response rate of 59%) and those who were crizotinib-naive (overall response rate of 62%). 78 patients were treated at 750mg/day; 36 patients were treated with LDK378 at 400-750mg/day. The median duration of response for patients treated at 400mg/day or higher (n=66) was 8.2 months (95% confidence interval [CI], 6.9-NE), with a median progression-free survival of 8.6 months (95% CI; 5.7-9.9). The six-month duration of response rate at 750mg/day was 61% (95% CI; 34.9-78.8). This trial will serve as the basis for the first regulatory filing, anticipated in early 2014.
June 17, 2013
DelMar Pharmaceuticals reported results from a phase I/II trial of VAL-083 (dianhydrogalactitol) for the treatment of recurrent malignant glioma and progressive secondary brain tumors. Of the three cohorts of patients currently enrolled, all have failed standard therapies and have no viable treatment options. The subjects received VAL-083 at a dose of 1.5mg/m; 3.0mg/m and 5.0mg/m. At these doses, 25% (2/8) of GBM patients and 17% (1/6) of secondary-progressive brain cancer patients showed stable disease or tumor regression in response to treatment. VAL-083 therapy is well tolerated in glioblastoma multiforme (GBM) and secondary-progressive brain tumor patients with no drug-related serious adverse events at doses studied to date. DelMar plans to split the protocol into two separate studies: one focusing solely on refractory glioblastoma and the other focusing on metastatic brain cancers.
Halozyme Therapeutics reported results from a phase Ib trial of PEGPH20 (PEGylated Recombinant Human Hyaluronidase) for the treatment of stage IV metastatic pancreatic cancer. The single-arm phase Ib trial enrolled 28 stage IV treatment naïve pancreatic ductal adenocarcinoma patients. The overall response rate (complete response + partial response) by RECIST 1.1 criteria was 42% (95% CI 22-62) for those treated at therapeutic dose levels of PEGPH20 (1.6 and 3.0μg/kg) as assessed by an independent radiology review (n=24). Additionally, in subjects with high levels of hyaluronan (HA), a substance found in a protective matrix that surrounds many pancreatic cancers, the overall response rate was 64% (seven of 11 subjects with available biopsy). Moreover, 43% (six of 14 subjects) saw a reduction of at least 70% in serum carbohydrate antigen 19-9 (CA 19-9), a biomarker that often correlates with tumor cell burden. Treatment was generally well tolerated, and the adverse event profile was consistent with those seen in previous studies of PEGPH20 as a single agent and as previously reported for gemcitabine alone. The most common adverse events were muscle spasms, myalgia and arthralgia (all grade 1/2). There was no evidence of new toxicities when used in combination with gemcitabine. The results support the dosing regimen at 3μg/kg, being used in the phase II trial.
June 10, 2013
Boehringer Ingelheim issued results from a phase III trial of LUME-Lung 1 for the treatment of advanced non-small cell lung cancer (NSCLC). This randomized, openlabel, double-blind study enrolled 1,314 patients with locally advanced or metastatic (stage IIIb/IV or recurring) NSCLC after first-line therapy. The subjects received nintedanib 200mg BID plus docetaxel 75mg/m(2) once a day for three weeks (n=655), or docetaxel plus placebo (n=659). LUME-Lung 1 improved progression-free survival (PFS)—the primary endpoint—as a second-line treatment in patients with NSCLC compared to docetaxel alone. Secondary endpoints included overall survival. Results showed patients treated with nintedanib plus docetaxel lived for a median of 3.4 months before their tumor started to grow again, versus 2.7 months with docetaxel alone (HR 0.79; p=0.0019). The most common adverse events (AEs) of any grade in the nintedanib combination and docetaxel alone groups were diarrhea (42.3% v. 21.8%, respectively) and ALT elevations (28.5% v. 8.4%, respectively). Incidence of > grade 3 AEs was 71.3% in patients treated with nintedanib plus docetaxel compared to 64.3% with docetaxel alone. A higher incidence of > grade 3 diarrhea and elevated ALT were observed in patients treated with nintedanib plus docetaxel compared to docetaxel alone (> grade 3 diarrhea: 6.6% v. 2.6%; elevated ALT: 7.8% v. 0.9%). Incidence of > grade 3 hypertension, bleeding and thrombosis were similar in both treatment arms. There was a 1% difference in discontinuation between the treatment arms, with 22.7% of patients stopping treatment with nintedanib plus docetaxel versus 21.7% with docetaxel alone.
Novartis reported results from a phase III trial of Afinitor for the treatment of HER2 positive advanced breast cancer. This randomized, double-blind study of everolimus plus trastuzumab and vinorelbine conducted at 159 clinical trial sites globally included 569 women with HER2 positive locally advanced or metastatic breast cancer who were previously treated with a taxane and were resistant to trastuzumab. Subjects received either everolimus 5mg/day orally or placebo, plus weekly vinorelbine 25mg/m IV and weekly trastuzumab 2mg/kg IV following a loading dose of 4mg/kg. The primary endpoint of significantly extended progression-free survival (PFS) when compared to treatment with placebo plus trastuzumab and vinorelbine was met. Final PFS results showed adding everolimus to the standard treatment of trastuzumab and vinorelbine reduced the risk of disease progression by 22% (hazard ratio=0.78 [95% confidence interval (CI):0.65 to 0.95]; p<0.01). Median time to progression was 7.0 months in the everolimus combination arm and 5.8 months in the placebo combination arm. Adverse events were consistent with the known safety profile of everolimus. The most common all-grade adverse reactions (incidence >30%) were neutropenia, stomatitis, anemia, leukopenia, fatigue, pyrexia, diarrhea, nausea, decreased appetite and constipation.
May 20, 2013
Syndax Pharmaceuticals published results from a phase II trial of entinostat for the treatment of estrogen receptor-positive (ER+) breast cancer in the Journal of Clinical Oncology. This randomized, double-blind, placebo-controlled study, ENCORE 301, enrolled 130 postmenopausal women with ER+ breast cancer whose cancer had progressed after treatment with a nonsteroidal aromatase inhibitor. Subjects received 25mg exemestane daily plus 5mg entinostat once per week, or 25mg exemestane plus placebo. Based on intent-to-treat analysis, patients treated with entinostat saw improved median progression-free survival to 4.3 months versus 2.3 months in patients treated with placebo (hazard ratio 0.73; 95% confidence interval, 0.50 to 1.07; one-sided p=.055; two-sided p=.11). Overall survival was an exploratory endpoint, and median survival improved to 28.1 months in entinostat-treated patients versus 19.8 months in placebo-treated (hazard ratio 0.59; 95% confidence interval, 0.36 to 0.97; p=.036). Entinostat was well tolerated. The most frequent adverse events were fatigue and neutropenia. Based on this data, Syndax Pharmaceuticals is working to move entinostat into a confirmatory pivotal study this fall.
May 13, 2013
Amgen issued results from a phase III head-to-head trial of Vectibix (panitumumab) versus Erbitux (cetuximab) for chemorefractory metastatic colorectal cancer (mCRC). This global, randomized, parallel-assignment, open-label, non-inferiority study enrolled 1,010 patients with mCRC with wild-type KRAS tumors. Subjects received 6mg/kg of intravenous Vectibix every 14 days or 400mg/m2 of an initial dose of intravenous Erbitux followed by 250mg/m2 of intravenous Erbitux every seven days. Data demonstrated the estimated overall survival hazard ratio (Vectibix/Erbitux) was 0.966 (95% CI: 0.839, 1.113) favoring the Vectibix arm. Vectibix was well tolerated. Overall, the relative adverse event profiles were as anticipated for each of the anti-EGFR therapies studied, including known events such as rash, diarrhea and hypomagnesemia.
April 15, 2013
Navidea Biopharmaceuticals issued interim results from a phase III trial of Lymphoseek (technetium 99m tilmanocept) for identifying sentinel lymph nodes (SLNs) in patients with head and neck squamous cell carcinoma. This open-label, multicenter, within-patient study, NEO3-06, enrolled 80 patients with head and neck squamous cell carcinoma. After receiving a Lymphoseek injection, 39 of the 80 patients were determined to have pathology-positive lymph nodes. Results demonstrated of these 39 patients, Lymphoseek accurately identified 38, for an overall False Negative Rate (FNR) of 2.56%, which was statistically significant (p=0.0205) and met the statistical threshold for success of the primary endpoint. Moreover, multiple-level nodal dissection of patients in the trial with cancer-positive lymph nodes led to an average removal of 38 lymph nodes per patient, whereas Lymphoseek on average led to the removal of approximately four lymph nodes, representing a substantial reduction in potential morbidity for patients with head and neck cancer undergoing sentinel lymph node biopsy. Based on these data, Navidea Biopharmaceuticals will evaluate the possibility of filing a Supplemental New Drug application (sNDA) later this year.
March 25, 2013
GTx published results from a phase II trial of enobosarm for the treatment of muscle wasting and physical function in cancer in The Lancet Oncology. This multi-center, randomized, double-blind, placebo-controlled study enrolled 159 patients who had been diagnosed with non-small cell lung cancer (NSCLC), colorectal cancer (CRC), non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) or breast cancer and who had not yet begun chemotherapy or were between chemotherapy cycles. Subjects received 1mg or 3mg enobosarm orally daily, or placebo, for up to 113 days. Data demonstrated patients receiving enobosarm (either 1mg or 3mg) showed a statistically significant increase from baseline to Day 113/end of trial in total lean body mass and a significant improvement from baseline in the time and power to climb 12 stairs. Patients receiving placebo during the same period did not show significant increases in total lean body mass or in physical function. Although the trial was not powered to assess survival, in a post-hoc analysis the survival hazard ratio for patients receiving enobosarm 1mg versus placebo was 0.80 and for those receiving enobosarm 3mg versus placebo was 0.70, representing a 20% and 30% improvement in survival, respectively. Enobosarm was well tolerated. The most frequent adverse events were similar among placebo and treatment groups. Based on this data, GTx has initiated two phase III trials of 3mg enobosarm in muscle wasting in patients with NSCLC.
March 4, 2013
Peregrine Pharmaceuticals issued results from a phase II trial of bavituximab for the treatment of non-small cell lung cancer (NSCLC). This Peregrine's randomized, double-blind, placebo-controlled study enrolled 121 patients with previously treated locally advanced or metastatic second-line NSCLC. Subjects received bavituximab 3mg/kg plus docetaxel or placebo plus docetaxel. Results showed a meaningful improvement in median overall survival of 11.7 months in the bavituximab plus docetaxel arm compared to 7.3 months in the control arm (HR=0.73; p value=0.217). Persistent separation in the survival curves was observed with response rates and progression-free survival also favoring the bavituximab plus docetaxel. Bavituximab was well tolerated. The most frequent adverse events were similar between both treatment arms. Based on these data, Peregrine is preparing for an end-of-phase II meeting with the FDA.
February 25, 2013
Argos Therapeutics reported results from a phase II trial of AGS-003 for metastatic renal cell carcinoma (mRCC). This open-label study enrolled 21 patients with unfavorable risk mRCC and with an expected survival of approximately 15 months. Subjects received standard six-week cycles of sunitinib plus AGS-003, administered every three weeks for five doses, and then every 12 weeks until progression. Results showed median overall survival was 30.2 months. When analyzed by baseline Heng risk status, the median overall survival for intermediate risk patients (n=11) has not been reached, but is estimated to be longer than 39.5 months with continued follow-up. Median overall survival for poor risk patients (n=10) was 9.1 months. Of the 21 patients who participated in the study, seven (33%) patients are still alive after nearly four years or longer following study registration. Argos Therapeutics is currently enrolling patients in a global phase III study of AGS-003.
Progenics Pharmaceuticals released results from a phase I trial of PSMA ADC for prostate cancer. This open-label, dose-escalation study enrolled 52 men with metastatic castration-resistant prostate cancer that had progressed despite prior treatment with taxane-based chemotherapy regimens. Subjects received nine different dosing levels of PSMA ADC administered at three-week intervals for 12 weeks. Significant antitumor activity was observed across doses ranging from 1.8mg/kg to 2.8mg/kg. PSMA ADC was generally well tolerated in patients at doses up to and including 2.5mg/kg, the maximum tolerated dose. Dose limiting toxicities, primarily neutropenia, were seen at 2.8mg/kg. The most frequent adverse events were anorexia and fatigue. Progenics Pharmaceuticals initiated a phase II, open-label, multicenter study of PSMA ADC.
February 18, 2013
AVEO Oncology and Astellas Pharma reported results from a phase III trial of tivozanib compared to sorafenib for the treatment of advanced renal cell carcinoma (RCC). This global, randomized study, TIVO-1, enrolled 517 patients with RCC. Subjects received either tivozanib or sorafenib. The final overall survival (OS) analysis showed a median OS of 28.8 months (95% confidence interval [CI]: 22.5–NA) for tivozanib versus a median OS of 29.3 months (95% CI: 29.3–NA) for the comparator arm, sorafenib. No statistical difference between the two arms (HR=1.245, p=0.105) was observed. Patients randomized to the sorafenib arm were eligible to cross over to tivozanib therapy under a separate protocol after radiographic confirmation of disease progression. No crossover protocol was available for patients randomized to the tivozanib arm. Tivozanib was well tolerated. Based on these data, AVEO and Astellas have filed a New Drug Application (NDA) for tivozanib for the treatment of RCC.
Peregrine Pharmaceuticals released results from a phase II trial of bavituximab in combination with gemcitabine Stage IV pancreatic cancer. This open-label, randomized study enrolled 70 patients with previously untreated, advanced Stage IV pancreatic cancer. Subjects received either bavituximab in combination with gemcitabine, or gemcitabine alone. Data demonstrated the combination of bavituximab and gemcitabine resulted in more than a doubling of overall response rates (ORR) and an improvement in overall survival (OS) when compared with gemcitabine. Subjects treated with a combination of bavituximab and gemcitabine had a 28% tumor response rate as compared to 13% in the control arm. Median OS, the primary endpoint of the trial, was 5.6 months for the bavituximab plus gemcitabine arm and 5.2 months for the control arm (HR=0.75). Bavituximab was generally safe and well tolerated, with similar adverse events occurring in both arms. Peregrine is evaluating the next steps for advancing the bavituximab pancreatic program to include combination with other cancer agents. Bavituximab is currently being evaluated in patients with non-small cell lung, breast, prostate, liver and rectal cancers in combination with approved chemotherapies and radiation.
February 4, 2013
Amgen issued results from a phase III trial of Neulasta (pegfilgrastim) for the treatment of colorectal cancer. This multinational, randomized, double-blind, placebo-controlled trial enrolled 845 patients receiving FOLFOX or FOLFIRI and bevacizumab for the first-line treatment of locally-advanced or metastatic colorectal cancer. Subjects received 6mg of Neulasta, or placebo, at least 24 hours after each cycle of chemotherapy. Results showed the study met its primary endpoint: Neulasta significantly reduced the incidence of febrile neutropenia (low white blood cell count accompanied by a fever). In the study, the incidence of grade 3 or 4 febrile neutropenia in patients receiving Neulasta across the first four cycles of chemotherapy was 2.4%, compared to 5.7% in the placebo group (OR=0.41, p=0.014). A similar incidence of grade 3 or higher adverse events was seen in both arms of the trial (28% placebo; 27% Neulasta). The drug was well tolerated. Amgen did not note its plans for Neulasta.
January 28, 2013
Celgene International issued results from a phase III trial of Abraxane in combination with gemcitabine for the treatment of metastatic pancreatic cancer. This open-label, randomized, international study, MPACT, enrolled 861 treatment-naïve patients with metastatic pancreatic cancer. Subjects received 125mg/m2 Abraxane plus 1000mg/m2 gemcitabine for three weeks, followed by a week of rest, or 1000mg/m2 gemcitabine alone for seven weeks, followed by a week of rest. Data demonstrated a statistically significant improvement in overall survival in the Abraxane/gemcitabine arm compared to patients receiving gemcitabine alone (median of 8.5 vs. 6.7 months) (HR 0.72, p=0.000015). Results showed the Abraxane/gemcitabine arm demonstrated a 59% increase in one-year survival (35% versus 22%, p=0.0002) and demonstrated double the rate of survival at two years (9% versus 4%, p=0.02) as compared to gemcitabine alone. Furthermore, the Abraxane/gemcitabine arm demonstrated a 31% reduction in the risk of progression or death with a median progression-free survival of 5.5 versus 3.7 months (HR 0.69, P=0.000024) and an overall response rate of 23% compared to 7%. The drug was well tolerated. The most frequent adverse events were neutropenia, fatigue and neuropathy. Based on these results, Celgene International plans to submit dossiers for registration in the U.S. and Europe during the first half of 2013, followed by submissions in other countries/regions during the second half of 2013.
January 7, 2013
Bristol-Myers Squibb reported results from a phase II trial of elotuzumab in combination with lenalidomide and low-dose dexamethasone for the treatment of multiple myeloma. This randomized, multi-center, open-label study enrolled patients with previously treated multiple myeloma. Subjects received either 10mg/kg or 20mg/kg of elotuzumab intravenously on days 1, 8, 15 and 22 of a 28-day cycle in the first two cycles, and then on days 1 and 15 of subsequent cycles. Subjects also received lenalidomide 25mg PO daily on days 1 to 21 and dexamethasone 40mg PO weekly. Results demonstrated in the 10mg/kg arm, median progression-free survival (PFS) was not reached after 20.8 months of follow up (n=36) and the objective response rate (ORR; according to the International Myeloma Working Group response criteria) was 92%. Of patients who received elotuzumab at a dose of 20mg/kg, median PFS was 18.6 months (n=37) and ORR was 76%. Elotuzumab was well tolerated. The most frequent adverse events were lymphopenia, neutropenia, thrombocytopenia, anemia, leukopenia, hyperglycemia, pneumonia, diarrhea, fatigue and hypokalemia. BMS also is studying elotuzumab in two phase III trials for treatment of relapsed/refractory multiple myeloma.
December 17, 2012
Boehringer Ingelheim issued preliminary results from a phase II trial of volasertib for the treatment of acute myeloid leukemia (AML). This open-label study enrolled 87 patients with newly-diagnosed AML who were considered ineligible for intensive remission induction therapy. Subjects received volasertib in combination with low-dose cytarabine (LDAC) (n=42) or LDAC alone (n=45). Results showed objective responses were observed in 31% of patients (13/42) treated with the combination of volasertib plus LDAC compared with 13.3% of the patients (6/45) treated with LDAC alone (odds ratio: 2.91; p=0.0523). The median time to remission was 71 (29158) days and 64 (30125) days, respectively. Data also showed that in patients treated with the combination of volasertib plus LDAC, the median event free survival was approximately 5.6 months (170 days) compared with approximately 2.3 months (69 days) in patients treated with LDAC alone (hazard ratio: 0.56; 95% CI: 0.34, 0.93; p=0.0237). Volasertib was well tolerated. The most frequent adverse events were gastrointestinal events, general events, infections, febrile neutropenia, metabolism/nutrition events and respiratory/thoracic/mediastinal events. Based on these data, Boehringer Ingelheim intends to begin recruitment of a phase III study of volasertib in combination with LDAC compared with LDAC alone in early 2013.
Celgene International released results from a phase I trial of CC-486 (oral azacitidine) for the treatment of myelodysplastic syndromes (MDS). This multi-arm study enrolled 53 patients with lower-risk MDS who were red blood cell transfusion-dependent and/or thrombocytopenic. Subjects received 300mg of CC-486 once daily for either 14 or 21 days of each 28-day cycle. After a median of seven treatment cycles for the 14-day treatment arm and five for the 21-day treatment arm, the overall response rate was 42.3% (11/26) and 37.0% (10/27), respectively. Additionally, the percentage of patients showing any hematologic improvement was 26.9% in the 14-day arm and 29.6% in the 21-day arm. The percentage of patients who sustained RBC transfusion independence for 56 days was 53.5% in the 14-day arm and 40.0% in the 21-day arm. The percentage of patients who sustained RBC transfusion independence for 84 days was 20% in the 14-day arm and 33.3% in the 21-day arm. CC-486 was well tolerated. The most frequent adverse events were anemia, thrombocytopenia, neutropenia and febrile neutropenia. Based on these and other early-stage data evaluating CC-486, Celgene plans to initiate two phase III studies (QUAZAR program) evaluating this oral agent in lower-risk MDS and acute myeloid leukemia by the end of 2012.
December 10, 2012
ARIAD Pharmaceuticals released results from a phase I trial of ponatinib for the treatment of resistant and refractory chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). This dose-escalation study enrolled 81 patients with resistant hematologic cancers, including 60 patients with CML and five patients with Ph+ ALL, who had become resistant to one or more tyrosine kinase inhibitors. Results showed that after 73 weeks, 72% of patients (31 of 43) with chronic-phase CML had a major cytogenetic response (MCyR), including 92% (11 of 12) who had the T315I gatekeeper mutation, the most common mutation among resistant patients. In addition, of 22 patients with accelerated-phase or blast-phase CML or Ph+ ALL, 36% (8 of 22) had a major hematologic response and 32% (7 of 22) had aMCyR. The drug was well tolerated. The most frequent adverse events were rash, thrombocytopenia, arthralgia, increased lipase, fatigue, acneiform dermatitis dry skin and nausea. ARIAD did not disclose its plans for ponatinib.
November 28, 2012
Aeterna Zentaris reported results from a phase I trial of perifosine combined with temsirolimus for the treatment of malignant glioma. This combination, dose-ranging study enrolled 32 patients with recurrent or progressive malignant glioma, anaplastic astrocytoma, anaplastic oligodendroglioma and transformed low-grade gliomas with median Karnofsky Performance Status 80. Subjects either received a 600mg or 900mg dose of perifosine on day one, followed by a nightly dose of 100mg of perifosine. All subjects also received 15mg to170mg of temsirolimus once weekly. Preliminary survival results demonstrated that median overall survival was 7.4 months. There were 27 radiographic responses: complete response (0), partial response (2), stable disease (13) and progressive disease (12). The most frequent adverse events were hypophosphatemia, hypocholesterolemia and hypertriglyceridemia. The maximum tolerated dose was not defined, so Aeterna Zentaris is creating expansion cohorts.
OncoSec Medical issued preliminary results from a phase II trial of ImmunoPulse for the treatment of metastatic melanoma. This single-arm, open-label and multi-center study has enrolled 13 patients with stage III or IV cutaneous and in-transit metastatic melanoma, of 25 patients expected. Subjects received a maximum dose of 1.5mg of DNA IL-12 via ImmunoPulse on days one, five and eight, applied to up to four lesions. Subjects also received electroporation treatment. Results suggested that ImmunoPulse is able to induce regression or stabilization of distant untreated metastases following a single cycle of treatment. Ninety-five percent of treated lesions demonstrated response at day 39 (5% progressive disease, 14% stable disease (SD), 42% partial response (PR), 39% complete response (CR)). All treated lesions at day 90 (5% SD, 50% PR, 45% CR), and at day 180 (33% PR, 67% CR) demonstrated a response. At day 180, two subjects were evaluable for the primary endpoint of objective overall response (ORR). One patient has a confirmed stable disease, and the second patient has a confirmed complete response of all treated and untreated lesions. ImmunoPulse and DNA IL-12 were well tolerated. The most frequent adverse events were generally limited to transient pain related to electroporation treatment. OncoSec Medical will continue the phase II study, which it expects to be completed by the end of 2012.
November 12, 2012
MorphoSys and Xencor released results from a phase I/IIa trial of MOR208 (MOR00208/XmAb5574) for the treatment of tumor activity. This dose-ranging study enrolled patients with high-risk, heavily pretreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Subjects received doses ranging from MOR208 0.3mg/kg to 12mg/kg as an intravenous infusion on days 1, 4, 8, 15 and 22 in cycle one, and on days 1, 8, 15 and 22 in cycle two. Overall response rate by International Working Group on CLL (IWCLL) 2008 criteria was 11%, which utilizes more rigorous CT scan reduction of internal lymph nodes not previously required in older historic studies. Using IWCLL 1996 response criteria resulted in a response rate of 42%. MORE208 was well tolerated and found safe. The most frequent adverse events were mild to moderate infusion reactions usually with the first dose. Based on these results, MorphoSys plans to commence phase II studies of MOR208 in B-cell malignancies in the near future.
November 5, 2012
Alliance for Clinical Trials in Oncology released results from a phase III trial of doxepin for the treatment of head and neck cancer. This multi-institution, randomized, double-blind, placebo-controlled study enrolled 140 patients who were also receiving radiation therapy for their head and neck cancer (>50.0Gy), which involved more than one-third of the oral cavity. Subjects received a single, blinded dose of doxepin rinse (doxepin 25mg in 5ml of water) or placebo on day one, and then crossed over to the opposite study group on a subsequent day. Results indicated that the addition of doxepin significantly decreased pain, which was measured by the area under the curve (AUC) on the pain scale over time. Patients who received doxepin reported a reduction in pain to a -9.1 versus -4.7 for those who received the placebo. Analysis of the crossover data revealed similar findings, with an AUC score of -7.9 in the doxepin group versus -5.6 in the placebo group. Sixty-four percent of patients elected to continue doxepin after the study was completed. Doxepin was well tolerated. The most frequent adverse events were stinging/burning, unpleasant taste and greater drowsiness.
Specialised Therapeutics Australia issued results from a phase III comparative trial of Abraxane versus standard chemotherapy for the treatment of metastatic melanoma. This randomized, open-label, international study enrolled 529 chemotherapy-naïve patients. Subjects received either Abraxane 150mg/m2 weekly for three out of four weeks, or dacarbazine 1000mg/m2 every three weeks. The Abraxane arm showed statistically significant improvement in progression-free survival (PFS) (4.8 months) compared to patients receiving dacarbazine chemotherapy (2.5 months) (HR:0.792; 95.1% CI: 0.631, 0.992; P=0.044). Data shows overall survival trends in favor of the Abraxane arm (12.8 months) compared to dacarbazine (10.7 months) (HR:0.831; 99.9% CI: 0.578, 1.196; P=0.094). The drug was well tolerated. The most frequent adverse events were neuropathy and neutropenia. Specialised Therapeutics Australia hopes to have Abraxane approved by the Therapeutic Goods Administration in Australia by 2014.
October 29, 2012
Celgene International reported results from a phase III trial of pomalidomide plus low-dose dexamethasone compared to high-dose dexamethasone for multiple myeloma. This multi-center, randomized, open-label study enrolled patients with relapsed and/or refractory multiple myeloma. Subjects in Arm 1 received 4mg pomalidomide on days 1-21 of each 28-day cycle, with patients 75 years or younger also receiving 40mg of low-dose dexamethasone and patients older than 75 receiving 20mg of low-dose dexamethasone on days 1, 8, 15 and 22 of each 28-day cycle, until disease progression. Subjects in Arm 2 received 40mg high-dose dexamethasone on days 1-4, 9-12 and 17-20 of each 28-day cycle if they were 75 years or younger, and patients older than 75 received 20mg high-dose dexamethasone on days 1-4, 9-12 and 17-20 of a 28-day cycle, until disease progression. The study met its primary endpoint of improvement in progression-free survival (PFS) at the PFS final analysis. Additionally, the study crossed the superiority boundary for overall survival (OS), a key secondary endpoint. As a result, patients who had not yet progressed in the high-dose dexamethasone arm should be crossed-over to the pomalidomide plus low-dose dexamethasone arm. Celgene has submitted an NDA application to the FDA, as well as an MAA application to the EMA.
October 15, 2012
Boehringer Ingelheim released results from a phase III trial of afatinib for the treatment of non-small cell lung cancer (NSCLC). This randomized, open-label study enrolled 345 previously untreated patients with EGFR mutation positive NSCLC. Subjects received afatinib or standard chemotherapy agents (pemetrexed/cisplatin) as first-line treatment. Data showed afatinib-dosed patients had a progression-free survival (PFS) of 11.1 months versus a PFS of 6.9 months for those receiving pemetrexed/cisplatin. NSCLC patients with tumors harboring the two most common EGFR mutations (del19 and L858R) receiving afatinib had a PFS of 13.6 months versus a PFS of 6.9 months for those in the comparator arm. The afatinib-dosed arm experienced an improvement in shortness of breath, cough and chest pain, a delay in deterioration of these symptoms, and overall improved quality of life. Afatinib was well tolerated. Boehringer Ingelheim has initiated two head-to-head trials comparing afatinib to Iressa (gefitinib) and Tarceva (erlotinib), to demonstrate any potential efficacy and safety superiority.
October 1, 2012
Cell Therapeutics reported results from a phase I trial of pacritinib (SB1518) for the treatment of relapsed/refractory lymphoma. This multi-arm, dose-finding study enrolled 34 patients with relapsed or refractory Hodgkin’s or non-Hodgkin’s lymphoma of any type except Burkitt’s or CNS lymphoma. Subjects received pacritinib ranging from 100mg to 600mg daily. Data showed the maximum dose was not met. Pacritinib inhibited JAK2 signaling at all dosing levels and FLT-3 inhibition were seen in most patients. Seventeen of the 34 patients (50%) had measurable decreases in target tumor measurements ranging from 4% to 70% shrinkage. Partial remissions were noted in three patients (mantle cell and indolent lymphoma), while 15 patients had stable disease. Median progression-free and overall survival was 120 and 130 days, respectively. Pacritinib was well tolerated. The most frequent adverse events were gastrointestinal. Based on these data, Cell Therapeutics will continue with efficacy studies of JAK/STAT pathway inhibitors, either alone or in combination regimens.
September 24, 2012
Jennerex reported results from a phase II trial of JX-594 for the treatment of hepatocellular carcinoma (HCC). This nonrandomized study enrolled 25 Asian patients with advanced HCC; 20 were refractory to sorafenib and were treated with an intravenous dose of JX-594, while the majority of patients then received sequential intra-tumoral doses of JX-594 at week one and three. The majority subsequently received treatment with sorafenib. The study met its primary endpoint of determining the safety of JX-594 followed by sorafenib in patients with advanced HCC. After six or 12 weeks, 59% had disease control as measured by modified RECIST and 75% had objective responses by Choi criteria. 85% of patients had disease control by mRECIST or Choi response. The sequential treatment regimen was well tolerated with transient flu-like symptoms, with the most common adverse event being transient leukopenia. Jennerex is planning several phase II studies of JX-594 in liver cancer, HCC and colorectal cancer.
September 17, 2012
ImmunoGen released results from a phase II trial of IMGN901, in combination with etoposide and carboplatin, for the treatment of small cell lung cancer (SCLC). This randomized, dose-finding study, NORTH, enrolled 120 patients. Subjects received etoposide 100 mg/m2 on days one through three every 21 days; carboplatin AUC5 or AUC6 on day one every 21 days; and IMGN901 ranging up to 112 mg/m2, administered on days one and eight every 21 days. Results showed that IMGN901 112 mg/m2, carboplatin AUC5 and etoposide 100 mg/m2 was the most effective dose. Of the 33 patients dosed with this regimen, 10 had an objective response and 24 (72.7%) had disease control (objective response or stable disease). IMGN901 was well tolerated. The most frequent adverse event was low grade peripheral neuropathy.
August 27, 2012
Medivation and Astellas Pharma published results from a phase III trial of enzalutamide for the treatment of metastatic castration-resistant prostate cancer. This international, randomized, double-blind, placebo-controlled study, AFFIRM, enrolled 1,199 men who had been previously treated with docetaxel-based chemotherapy. Subjects received enzalutamide 160mg once daily (as four 40mg capsules), or placebo. Data showed enzalutamide exhibited a statistically significant benefit in overall survival compared to placebo. Men treated with enzalutamide had a median overall survival of 18.4 months (95% confidence interval, 17.3 to not yet reached) compared to 13.6 months (95% confidence interval 11.3-15.8) for men treated with placebo (hazard ratio 0.63; p<0.0001), representing a 37% reduction in the risk of death. The drug was well tolerated. The most frequent adverse events were fatigue, diarrhea and hot flush. Seizure was reported in less than 1% of enzalutamide-treated patients. Neither Medivation nor Astellas noted its next steps for enzalutamide.
August 6, 2012
Advaxis released interim results from a phase II trial of ADXS-HPV for the treatment of with recurrent/refractory cervical cancer. This multi-arm, randomized study has enrolled 63 female patients thus far who have failed previous cytotoxic therapy. Subjects received ADXS-HPV (1x109 cfu) with or without cisplatin 40mg/m2 weekly for five weeks. The primary endpoint, survival, at months six, nine and 12 is 64%, 46% and 29%, respectively, while the National Comprehensive Network Guidelines cite historical 12-month survival data of 0%-22% with single agent therapy in this patient population. Thus far, ADXS-HPV has triggered five complete responses (three in the ADXS alone group; two in the ADXS+ cisplatin group) and six partial responses (three in the ADXS alone group; three in the ADXS+ cisplatin group). A complete response is defined as 100% elimination of tumor burden, whereas a partial response is defined as 30% or more reduction in tumor burden. The drug was well tolerated. Advaxis is continuing the trial in India, and the Gynecologic Oncology Group plans to conduct a phase II study of ADXS-HPV in a similar patient population in the U.S.
July 9, 2012
Synta Pharmaceuticals reported interim results from a phase IIb/III trial of ganetespib in combination with docetaxel for the treatment of advanced non-small cell lung cancer (NSCLC). This multi-arm, randomized, open-label phase IIb part of the GALAXY study enrolled 183 patients to date with stage IIIB/IV NSCLC who have progressed following one prior line of therapy. All subjects received a standard regimen of docetaxel 75mg/m2 on Day 1 of a 21-day cycle; subjects in the combination arm receive in addition ganetespib 150mg/m2 on Day 1 and 15. Both primary endpoints were met based on RECIST 1.1 criteria. Subjects with elevated baseline level of serum LDH (lactate dehydrogenase) who received a combination of ganetespib and docetaxel had a median PFS of 4.2 months, compared to 1.4 months in those treated with only docetaxel; subjects with a tumor KRAS mutation receiving the combination treatment had a median PFS of 4.2 months, while the docetaxel group had a PFS of 1.6 months. The treatment was well tolerated. The most frequent adverse events were neutropenia, diarrhea and fatigue. Synta Pharmaceuticals will continue to enroll more subjects in the phase IIb trial. The transition into phase III is expected later this year.
June 9, 2008
Celator released positive results from a phase II trial of CPX-1 for the treatment of colorectal cancer. This multi-center, open-label study enrolled 59 subjects who were placed in two arms: irinotecan-naive (IRI-naive) and irinotecan-refractory (IRI-refractory) and received 210 units/m2 of CPX-1 every two weeks. In the IRI-naive arm the overall response rate was 8% and the disease control rate (response or stable disease) was 65 percent. Median progression- free survival (PFS) was 3.9 months and six subjects had a greater than six month PFS. In the IRI-refractory arm the disease control rate was 45%; there were no reports of an objective response. The median PFS was 2.3 months and three subjects had a greater than six month PFS. The 210 unit/m2 dose produced more toxicities than seen in previous phase 1 studies, resulting in only 40 percent of the subjects receiving more than 80 percent of the planned dose intensity. Hence, treatment will be initiated at a lower dose in future studies. Based on the results Celator plans to move forward with the development of CPX-1.
February 4, 2008
Pro-Pharmaceuticals reported positive results from a phase II trial of Davant for the treatment of colorectal cancer. This trial enrolled twenty previously heavily treated subjects, all of whom had at least two previous chemotherapy treatments including; fluorpyrimidines, Irinotecan, Oxaliplatin and Avastin or Erbitux. All subjects received Davant (280 mg/m2) in combination with 5-fluorouracil (5-FU, 500 mg/m2), given four times monthly until disease progression or unacceptable toxicity. The median progression free survival was 8.4 weeks and one subject reported an objective response. Treatment was generally well tolerated. There were seven reports of serious adverse events, however only two of these, anemia and dehydration, were considered to be drug related. Based on the results, Pro-Pharmaceuticals plans to move forward with the development of Davant.
pSivida issued positive results from a phase IIa trial of Brachysil for the treatment of pancreatic cancer. This trial enrolled seventeen subjects with advanced inoperable pancreatic cancer. The subjects received BrachySil, injected directly into the primary tumors via endoscopic ultrasound, in combination with standard chemotherapy (gemcitabine). CT assessments of response were performed at weeks eight, sixteen and twenty four. The combination treatment was well tolerated, with no significant adverse events related to BrachySil. Data showed disease control in 82% of subjects and an overall median survival of three hundred and nine days. In addition, BrachySil was found to be easily deliverable by endoscopic ultrasound. Based on the results, pSivida plans to commence a phase II dose ranging study in the first quarter of 2008.
November 26, 2007
Thallion reported positive results from a phase I/II trial of ECO-4601 for the treatment of advanced cancers. The trial enrolled twenty-six subjects who were refractory to their respective standard of care therapy. ECO-4601 was administered in twenty-one day cycles consisting of a two week continuous intravenous infusion followed by a one week rest period. The trial was conducted in two portions. In the first portion, fourteen subjects received escalating doses ranging from 30 to 480mg/m2/day to assess safety, pharmacokinetics and maximum tolerated dose. In the second portion of the trial, twelve subjects were treated at the highest dose, 480mg/m2/day. Treatment was well tolerated and the maximum target dose was attained before the maximum tolerated dose was reached. Pharmacokinetic data demonstrated that estimated therapeutic plasma concentrations of ECO-4601 were reached at the higher doses and that ECO-4601 was rapidly eliminated from the bloodstream following infusion. In addition, six of seven subjects with refractory cancer who had completed six cycles of treatment achieved stable disease. Based on the results, phase II trials were expected to be initiated in early 2008.
June 9, 2003
Agennix and Veterans Affairs Medical Center reported positive results from two phase I/II trials investigating Lactoferrin (rhLF), a natural protein found in milk, for the treatment of solid tumors. Data showed that 53% of evaluable subjects (10 /19) demonstrated stable disease, three of which showed tumor shrinkage. In addition, 29 subjects completed dosing, with only one withdraw due to disease progression. The saftey portion of the studies enrolled 30 subjects and evaluated rhLF as a single agent for the treatment of solid non-resectable tumor cancer patients, who had progressed on standard chemotherapy. Subjects were administered one of four different doses of rhLF, (1.5g to 9g), either for 14 days or in cycles of 14 days. The drug was well tolerated with no drug-related serious adverse events reported.
May 6, 2002
Phase II trial results suggest a strong correlation between clinical response and pharmacological action for GD0039, GlycoDesign's lead anti-cancer drug. The trial, which was conducted at five Canadian centers, included 18 subjects with metastatic renal cancer and 22 subjects with metastatic colorectal cancer resistant to 5-fluorouracil. In 14 trial subjects, the cell-surface carbohydrate structures targeted by GD0039 were highly inhibited. Within this population, four of six renal cancer subjects and three of eight colorectal cancer subjects experienced tumor shrinkage or stable disease.