April 11, 2016
BioLineRx issued results from BL-8040’s phase II trial in relapsed or refractory acute myeloid leukemia (r/r AML). The trial was a multicenter, open-label study assessing pharmacodynamics and pharmacokinetic parameters of BL-8040 in combination with Cytarabine (Ara-C). Forty-two patients with r/r AML were enrolled in the study (36 of which received a dose of 1mg/kg and higher). The study included a dose escalation stage followed by an expansion stage. Each patient received a once daily dose of BL-8040 monotherapy (from 0.5 to 2mg/kg) on days one to two, followed by the same dose of BL-8040 plus Ara-C on days three to seven. Extensive pharmacodynamic parameters, such as mobilization of leukemic cells and induction of apoptosis, were assessed after monotherapy with BL-8040 using peripheral blood sampling and bone marrow aspirates at baseline and on day three prior to Ara-C administration. Clinical response to treatment was evaluated by bone marrow biopsy on day 30. Results showed BL-8040, as a single agent and in combination with Cytarabine (Ara-C), was safe and well-tolerated at all doses tested up to and including the highest dose level of 2mg/kg, with no major adverse events (n=45). The composite complete remission rate, including both complete remission (CR) and complete remission with incomplete blood count recovery (CRi), was 38% in subjects receiving up to two cycles of BL-8040 treatment at doses of 1mg/kg and higher (n=39). The company plans multiple additional clinical studies for BL-8040. An AML consolidation treatment is currently being investigated in a large phase IIb study at in Germany.
April 4, 2016
Celator Pharmaceuticals reported results
of a phase III trial of VYXEOS (cytarabine:
daunorubicin) Liposome Injection (also
known as CPX-351) in patients with high-risk
(secondary) acute myeloid leukemia (AML)
compared to the standard of care regimen
of cytarabine and daunorubicin known as
7+3. The median overall survival for patients
treated with VYXEOS in the study was
9.56 months compared to 5.95 months for
patients receiving 7+3, representing a 3.61
month improvement in favor of VYXEOS.
The hazard ratio (HR) was 0.69 (p=0.005)
which represents a 31% reduction in the risk
of death versus 7+3. The percentage of patients
alive 12 months after randomization
was 41.5% on the VYXEOS arm compared to
27.6% on the 7+3 arm. The percentage of
patients alive 24 months after randomization
was 31.1% on the VYXEOS arm compared
to 12.3% on the 7+3 arm. VYXEOS
also demonstrated a statistically significant
improvement in induction response rate
(CR+CRi of 47.7% v. 33.3%; p=0.016) and
this significance was maintained for the
analysis of CR alone (CR of 37.3% v. 25.6%,
p=0.040). Sixty-day all-cause mortality was
13.7% v. 21.2%, in favor of patients treated
with VYXEOS. Based on these results the
company expects to submit an NDA for VYXEOS
with the FDA later this year and submit
an MAA with the EMA in the first quarter
of 2017. No substantial difference in Grade
3 or higher adverse events was observed
between VYXEOS and 7+3. In the intent-to-treat
population, Grade 3 or higher, hematologic
adverse events were similar for overall
infections, febrile neutropenia, and bleeding
events. In the intent-to-treat population,
Grade 3 or higher, non-hematologic adverse
events were similar across all organ systems,
including cardiac, gastrointestinal, general
systems, metabolic disorders, musculoskeletal,
nervous system, respiratory, skin and
January 18, 2016
Genentech reported results of a phase II
study of venetoclax for chronic lymphocytic
leukemia (CLL). The study met its primary
endpoint, with an overall response rate (ORR)
of 79.4% with venetoclax, as assessed by
an independent review committee (IRC). In
addition, 7.5% of people achieved a complete
response with or without complete
recovery (complete response without normal
blood counts) in the bone marrow. Forty-five
people had an assessment for minimal
residual disease (MRD) in the blood. Notably
18 people (17% of the total, 21% of responders)
achieved MRD-negativity, meaning no
cancer could be detected using a specific test.
Ten of these 18 people also had bone marrow
assessments and six were MRD-negative. At
one year, 84.7% of all responses and 94.4% of
MRD-negative responses were maintained.
The one-year progression-free survival (PFS)
and overall survival (OS) rates were 72% and
86.7%, respectively. No unexpected safety
signals were reported. AbbVie has submitted
an NDA for venetoclax to the FDA. Venetoclax
received Breakthrough Therapy designation
from the FDA earlier this year for the treatment
of people with relapsed or refractory
CLL harboring the 17p deletion. AbbVie also
has submitted a marketing authorization
application (MAA) to the EMA. Submissions to
other regulatory authorities around the world
are planned in 2016.
December 14, 2015
Janssen-Cilag International issued results of a randomized, multicenter, open-label, phase III trial of ibrutinib (IMBRUVICA) for treatment-naïve chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) in patients aged 65 or older. Patients were randomized to receive either ibrutinib 420mg orally, once daily until progression or toxicity or chlorambucil 0.5 to 0.8mg/kg on days one and 15 of each 28-day cycle for up to 12 cycles. The primary endpoint of the study was PFS as assessed by an IRC according to the International Workshop on Chronic Lymphocytic Leukaemia (iWCLL) 2008 criteria, with modification for treatment-related lymphocytosis. The Independent Review Committee (IRC) found ibrutinib significantly prolonged PFS compared with chlorambucil. The hazard ratio (HR) was 0.16 (95% CI, 0.09-0.28; P<0.001), which represents a reduction in the risk of progression or death by 84% v. chlorambucil (median not reached v. 18.9 months); the PFS rate at 18 months was 90% for ibrutinib v. 52% for chlorambucil. Ibrutinib also significantly prolonged OS (HR=0.16: 95% CI, 0.05, 0.56; P=0.001) with a 24-month survival rate of 98%, compared to 85% for patients in the chlorambucil arm. Additionally, ibrutinib was associated with a significantly higher ORR (86% v. 35%; P<0.001) as assessed by the IRC and significantly increased the rate of sustained improvements in both haemoglobin and platelets. The RESONATE-2 results are the basis for a Type II variation application to the EMA seeking to broaden the existing marketing authorization for IMBRUVICA to include previously untreated patients with CLL. Janssen affiliates market IMBRUVICA in EMEA (Europe, Middle East and Africa) as well as the rest of the world, except for the U.S., where Janssen Biotech, Inc. and Pharmacyclics co-market it.
August 10, 2015
Sunesis Pharmaceuticals issued results of
a phase III trial of vosaroxin and cytarabine in
711 patients with relapsed or refractory acute
myeloid leukemia (AML). VALOR is a randomized,
double-blind, placebo-controlled trial conducted
at 124 sites in 15 countries. Patients were
stratified for age, geographic region and disease
status and randomized one-to-one to receive
either vosaroxin and cytarabine or placebo and
cytarabine. Although no significant difference
was observed in the primary endpoint of overall
survival (OS) between groups (unstratified
analysis, median 7.5 months for vosaroxin and
cytarabine [vos/cyt] v. 6.1 months for placebo
and cytarabine [pla/cyt], HR=0.87, p=0.061),
OS was significantly prolonged in a predefined
analysis that stratified by factors used in randomization
(stratified log-rank p=0.024). This
was supported by a sensitivity analysis of OS
censoring for subsequent transplant (median
6.7 months [vos/cyt] v. 5.3 months [pla/cyt],
HR=0.81, p=0.024). Prespecified subgroup
analyses according to randomization strata
demonstrated that OS benefit with vosaroxin
was greatest in patients age =60 years (7.1
months [vos/cyt] v. 5 months [pla/cyt], HR=0.75;
p=0.0030). Median OS was not significantly
different between treatment arms in patients
age <60 years (HR=1.08; p=0.60). The complete
remission (CR) rate, the sole secondary efficacy
endpoint in the VALOR trial, was significantly
greater with vosaroxin (30.1% v. 16.3% with pla/
cyt, p<0.0001). Combined complete remission
rate was 37.1% and 18.6% for the vos/cyt and
pla/cyt treatment arms, respectively (p<0.0001).
Prespecified subgroup analyses demonstrated
significantly higher response rates for vos/cyt-treated
patients across all randomization strata
except for those less than 60 years of age, with
the most pronounced improvement in patients
aged =60 years (CR: 31.9% for vos/cyt vs 13.8%
for pla/cyt; p<0.0001). A higher proportion
of patients in the vos/cyt arm achieved CR
with study drug prior to transplant (48% vos/
cyt; 32% pla/cyt). In patients with CR, median
leukemia-free survival (LFS) was 11 months with
vos/cyt v. 8.7 months with pla/cyt (HR=0.89;
p=0.63). Event-free survival (EFS) was significantly
prolonged in vos/cyt-treated patients
(HR=0.67; p<0.0001). Thirty-day and 60-day
all-cause mortality was similar in the two treatment
arms (30-day: 7.9% v. 6.6%; 60-day: 19.7%
v. 19.4% for vos/cyt vs pla/cyt, respectively).
The company is proceeding with registration in
Europe and the U.S.
April 27, 2015
Novartis reported results of a phase III study
of Arzerra (ofatumumab) plus chlorambucil
in patients with chronic lymphocytic leukemia
(CLL) for whom fludarabine-based therapy
was considered inappropriate, mainly due to
advanced age or the presence of comorbidities.
This prospective, randomized, open-label, phase
III study included 447 patients with previously
untreated CLL. Patients were randomized 1:1 to
treatment with up to 12 cycles of ofatumumab
in combination with chlorambucil or up to
12 cycles of chlorambucil alone. In the study,
median PFS was improved by 71% in the group
receiving ofatumumab plus chlorambucil
compared to the chlorambucil alone group
(22.4 months v. 13.1 months, respectively; HR
0.57 [95% CI 0.45, 0.72]; p<0.0001). Improvement
in PFS was observed in most subgroups
irrespective of age, gender, disease stage and
prognostic factors. Additionally, patients in the
combination arm also experienced significantly
longer TTNT when compared to chlorambucil
alone (39.8 months v. 24.7 months, respectively;
HR 0.49 [95% CI: 0.36, 0.67]; p<0.0001). Patients
in the combination arm had a higher ORR (82%
of patients v. 69% of patients, respectively;
odds ratio 2.16 [95% CI: 1.36-3.42]; p=0.001),
with a better CR rate (14% of patients v. 1% of
patients, respectively). Compared to those on
chlorambucil alone, patients in the combination
arm had a duration of response of 22.1
months v. 13.2 months (HR 0.56 [95% CI: 0.43,
0.74]; p<0.001). More patients in the group
receiving ofatumumab plus chlorambucil (50%)
experienced adverse events (AEs) of grade
three or greater compared to chlorambucil
alone (43%), with neutropenia being the most
common adverse event (26% v. 14%). Grade 3/4
infusion-related reactions (IRRs) were reported
in 10% of patients receiving ofatumumab plus
chlorambucil, leading to drug withdrawal in 3%
of patients and hospitalization in 2% of patients.
No fatal IRRs were reported. These phase III data
formed the basis for regulatory approvals in the
U.S. and E.U. in 2014.
March 2, 2015
Pharmacyclics reported results of the phase
I portion of a phase I/IIb study of IMBRUVICA
(ibrutinib). Treatment with IMBRUVICA was associated
with an 88% overall response rate (ORR),
with a median time on study of 23.3 months, in
16 patients with relapsed/refractory (R/R) high-risk
chronic lymphocytic leukemia (CLL). These
patients had a median of five prior therapies and
63% were high-risk del 17p CLL patients. The estimated
median progression-free survival (PFS) at
24 months was 76.6%. All patients had previously
undergone allogeneic stem cell transplant. Pharmacyclics
now is enrolling the phase II portion at
the recommended phase II dose of 420mg.
January 19, 2015
Celator Pharmaceuticals issued results
of a phase II study of CPX-351 in adult
patients with first-relapse acute myeloid
leukemia (AML). The randomized, controlled
phase II study enrolled 125 patients, ages
18 to 65, from 35 centers in the U.S., Canada
and Europe diagnosed with AML in first
relapse after an initial complete remission
lasting for one month or longer. Patients
were randomized 2:1 to receive CPX-351
(100 u/m(2) days one, three and five by
90-minute infusion) or investigators’ choice
of first salvage chemotherapy. Control
salvage treatment was usually based on
cytarabine and an anthracycline, often with
one or more additional agents. The primary
endpoint for the study was survival at one
year post treatment. Patients were stratified
per the European Prognostic Index (EPI)
into favorable, intermediate and poor-risk
groups based on duration of first complete
remission, cytogenetics, age and transplant
history, and were well-balanced between
the control and the treatment arms. Results
showed improved efficacy following CPX-
351 and the protocol-defined EPI-poor-risk
subset demonstrated statistically significant
improvement in overall survival (HR, 0.55;
P=0.02), improvement in event-free survival
(HR, 0.63; P=0.08) and higher response
rate (39.3% v. 27.6%). Additionally, 60-day
mortality was lower in the CPX-351 study
arm for poor-risk patients (16.1% v. 24.1%).
CPX-351 currently is in phase III trials.
November 3, 2014
Novartis and the University of Pennsylvania’s
Perelman School of Medicine
reported results of two pilot trials evaluating
CTL019 in patients with relapsed/refractory
acute lymphoblastic leukemia (r/r ALL).
Twenty-five patients enrolled in the pediatric
pilot trial and five patients enrolled in the
adult pilot trial. The study found 27 of 30 pediatric
and adult patients with r/r ALL (90%)
experienced complete remissions, including
two blinatumomab-refractory patients and
15 with prior stem cell transplant. Of the 27
patients who achieved a complete remission,
five went off-study for alternate therapy,
three of whom proceeded to allogeneic
SCT in remission. Fifteen patients remain in
remission with a median follow-up of seven
months. Sustained remissions were achieved
up to two years with six-month, event-free
survival 67% (95% CI, 51% to 88%) and overall
survival 78% (95% CI, 65% to 95%). The
probability of six-month CTL019 persistence
was 68% (95% CI, 50 to 92%) and relapse-free
B cell aplasia was 73% (95% CI, 57 to 97%).
CTL019-modified T cells were detectable in
the blood by flow cytometry for up to 11
months, and CTL019 sequences remained
detectable by quantitative PCR (Q-PCR) in
patients with sustained remissions for up to
October 13, 2014
Erytech reported results of a phase III
study of Graspa for acute lymphoblastic
leukemia (ALL). The three-arm, controlled,
multicenter trial enrolled 80 children and
adults. The first two arms compared Graspa
to native E. Coli L-asparaginase, both in
combination with standard chemotherapy,
in a 1-to-1 randomization in patients without
prior allergies to L-asparaginase. The third
arm was an open-label assessment of Graspa
for patients who have experienced allergic
reactions related to asparaginase in their
first-line treatment. None of the 26 patients
in the Graspa arm experienced an allergic
reaction v. 12 of the 28 (42.9%) patients
treated with reference L-asparaginase in the
control group (p<001). In the Graspa group,
asparaginase levels were maintained above
100 IU/l for an average of 20.5 days with up
to two injections during the first month of
treatment (induction phase) v. 9.2 days in the
control group with up to eight injections of
reference L-asparaginase (p<001). At the end
of the induction phase, 15 patients (71.4%)
in the Graspa arm show complete remission
v. 11 patients (42.3%) in the control arm.
Erytech intends to submit an application to
the European Marketing Authorization in the
first half of 2015.
July 21, 2014
Boehringer Ingelheim released results of a phase II trial of volasertib for older patients with acute myeloid leukemia (AML). The open-
label study enrolled 87 adult patients (median age 75) with AML not considered suitable for intensive induction therapy. Patients were randomly assigned to receive either volasertib in combination with LDAC (n=42) or LDAC (n=45). Patients were randomized in a 1:1 ratio to receive the combination of LDAC plus volasertib 350mg intravenously over one hour on days one and 15 versus LDAC 20mg twice daily subcutaneously on days one to 10 alone. Cycles were scheduled every four weeks until progression, relapse, intolerance or patient/
investigator requested discontinuation. The study’s primary endpoint showed the objective response rate (complete remission or complete remission with incomplete blood count recovery) was more than doubled for patients receiving volasertib and LDAC versus LDAC alone (31% v. 13.3%, p=0.052). The trial showed patients treated with volasertib combined with LDAC had a median overall survival of eight months versus 5.2 months in patients treated with LDAC (p=0.047). Median event-free survival was prolonged in patients receiving volasertib and LDAC versus LDAC (5.6 months v. 2.3 months; p=0.021). Relapse-
free survival for volasertib and LDAC versus LDAC was 18.5 months versus 10 months. There is an ongoing phase III study initiated for volasertib.
June 23, 2014
Ambit Biosciences released results of a
phase II study of quizartinib (AC220) for
FLT3-ITD (+) relapsed or refractory acute
myeloid leukemia. A total of 76 subjects
were enrolled. Dosing was 30mg/day and
60mg/day. The CRc rate remained at 47%
(5% CR+CRp, 42% CRi). The rate of hematopoietic
stem cell transplantation (HSCT)
after quizartinib use remained at 34%. The
median overall survival was 20.9 weeks for
patients initially treated at 30mg/day and
25.4 weeks for patients at 60mg/day, with
24/38 patients censored as they remained
alive in follow-up at the time of the analysis.
In addition, the further follow-up now
shows 24 subjects were alive at >24 weeks
with four subjects alive >12 months. Overall,
the additional follow up continued to show
that both the 30mg and the 60mg doses of
quizartinib showed substantial activity in
terms of overall CRc rate and bridge to HSCT
with impact on improved median OS. The
safety profile is similar at both doses and
QTcF prolongation did not worsen with additional
duration of treatment and/or follow
up. There is a currently ongoing phase III
study of quizartinib (AC220).
June 16, 2014
AbbVie issued results of phase Ib trials of
ABT-199/GDC-0199 in combination with
rituximab for relapsed/refractory chronic
lymphocytic leukemia (CLL) and various
subtypes of non-Hodgkin’s lymphoma
(NHL). The phase I, open-label, multicenter,
international trial of ABT-199/GDC-0199 in
patients with relapsed/refractory CLL and
NHL enrolled 78 patients in the CLL arm and
62 patients in the NHL arm of the trial. In the
CLL arm, due to concerns of TLS, the initial
dose was reduced from 50mg to 20mg and
daily dosing was modified to a weekly rampup
period to the final dose of 400mg. A
ramp-up period with weekly dose increases
occurred from 20mg, 50mg, 100mg, 200mg
to the final recommended phase II dose
(RPTD) of 400mg. The overall response rate
(ORR) was 77%, with 23% achieving complete
response (CR). Of the 18 CR/CRi patients
(complete response with incomplete
blood count recovery), 11 were evaluated
for minimal residual disease (MRD) and six
were found to be MRD negative. The ORR for
patients with 17p deletion and F-refractory
CLL was 79% and 76%, respectively. ABT-
199/GDC-0199 as a monotherapy in patients
with relapsed/refractory CLL harboring the
17p deletion is under investigation in an
ongoing phase II clinical trial.
January 6, 2014
Janssen reported results of a phase Ib/II open-label, multi-center study of ibrutinib for the treatment of previously untreated chronic lymphocytic leukemia (CLL, N=29) or small lymphocytic lymphoma (SLL, N=2) in patients over age 65, assessing oral, once-daily ibrutinib 420mg (27 patients) or 840mg (4 patients). Progression-free survival (PFS) and overall survival (OS) rates at 24 months (based on Kaplan-Meier projections) were estimated to be 96.3% (95% CI, 76.5-99.5) and 96.6% (95% CI, 77.9-99.5) respectively. Efficacy data collected showed 71% (95% CI, 52.0-85.8) of patients treated with ibrutinib achieved an objective response (defined as a complete or partial response). Although estimates of PFS and OS were not reached at the median follow up of 22.1 months, it is estimated that more than 95% of patients would be alive and progression-free at two years. The median time to initial response was 1.9 months (IQR,1.5-7.4 months), while the median time to best response and complete response were 5.9 months (IQR,1.8-22.1 months) and 12 months (IQR, 7.1-15.6 months). Ibrutinib has been submitted to the EMA for the treatment of adult patients with relapsed or refractory CLL/SLL or adult patients with relapsed or refractory MCL.
April 15, 2013
Pharmacyclics reported results from a phase II trial of ibrutinib for relapsed and refractory chronic lymphocytic leukemia (CLL). This study enrolled 53 subjects with CLL, 24 who were treatment naïve and 29 who had a deletion of chromosome 17p. Subjects received ibrutinib for six months. Results showed ibrutinib demonstrated rapid and sustained disease control in blood, lymph nodes, spleen and bone marrow. After six months, 95% of patients experienced a reduction in lymph node size and all showed reduction in spleen enlargement, with a median reduction of 55%. In 26 patients, for whom a bone marrow biopsy was done, tumor infiltration decreased by 82%. The Progression Free Survival probability for these patients at 12 months was estimated to be 94%. Ibrutinib was well tolerated. The most frequent adverse events were diarrhea, fatigue and rash. Based on this data, the FDA has designated ibrutinib as a Breakthrough Therapy in CLL patients with deletion 17p.
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.
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.
May 28, 2012
Amgen reported results from a phase II trial of blinatumomab for the treatment of relapsed or refractory B-precursor acute lymphoblastic leukemia. This single-arm, dose-ranging study enrolled 36 subjects who had relapsed following treatment with standard front-line chemotherapy or allogeneic stem cell transplant. Subjects received a continuous intravenous infusion of blinatumomab at an initial dose of five or 15 micrograms per meter squared per day, ranging up to 30 micrograms for the remainder of the treatment for 28 days. The dosing period was followed by two weeks off therapy, and the process then repeated up to four more times. The trial achieved a high-rate of complete response or partial hematologic recovery in 26 (72%) of subjects. At the time of the analysis, median survival was 9.0 (8.2, 15.8) months with a median follow-up period of 10.7 months. In subjects who received the selected dose, median survival was 8.5 months. The drug was generally well tolerated. The most common adverse events were pyrexia, headache, tremor and fatigue. Amgen did not comment on future plans for blinatumomab.
June 21, 2010
Micromet issued positive results from a phase II trial of blinatumomab for minimal residual disease (MRD) positive acute lymphoblastic leukemia (ALL). This trial enrolled 21 subjects who had sub-microscopic evidence of leukemic cells in the bone marrow following treatment with front-line chemotherapy (minimal residual disease). The subjects received 15 micrograms per meter squared per day of blinatumomab for 28 days followed by two weeks off therapy over a six week treatment cycle. The primary endpoint was MRD response. Of 20 evaluable patients, 80% achieved a complete MRD response. Among 13 non-transplanted patients, there were eight with non-Ph+ or t(4;11) disease. For these eight subjects the median time to hematological relapse has not been reached at a median follow-up of 480 days. Six of nine evaluable, MRD responding, non-transplanted patients were in hematologic remission, ranging up to 23 months. Eight of the subjects received an allogeneic transplant after blinatumomab treatment, all of whom are alive and in remission, ranging up to 21 months. Overall, blinatumomab was well-tolerated.
January 15, 2007
Kosan issued positive preliminary results from a phase II trial of tanespimycin plus Herceptin for the treatment of Herceptin-refractory HER2-positive metastatic breast cancer. This trial was designed to determine the objective response rate according to RECIST criteria in subjects with HER2-positive metastatic breast cancer with tumor progression during treatment with one Herceptin-containing regimen immediately prior to entering the trial. The trial enrolled 12 subjects who received tanespimycin (450 mg/m2) via a two-hour weekly intravenous infusion administered along with the standard dose of Herceptin. Treatment was well tolerated, with adverse events mild in nature. Of the eight subjects evaluable for efficacy, five (63%) showed signs of clinical benefit and three who had received 4-6+ cycles of treatment had stable disease. Based on the results Kosan plans to advance the development of tanespimycin into phase III trials.
Vertex and Merck announced positive results from a phase I trial of VX-680 (MK-0457) for the treatment of resistant leukemias and myeloproliferative diseases. This trial enrolled 44 subjects with chronic myelogenous leukemia (CML), Philadelphia chromosome-positive acute lymphocytic leukemia (Ph+ ALL), or myeloproliferative diseases (MPD). Subjects were treated with VX-680 given as a five-day intravenous infusion every two-to-three weeks. No treatment related toxicities were reported and thus the maximum tolerated dose was not yet determined. Out of the 15 subjects with CML, nine had a T315I BCR-ABL mutation. Eight of these nine T315I subjects had either a hematologic and/or cytogenetic response to VX-680 following multiple cycles of treatment. The six subjects without the T315I BCR-ABL mutation did not exhibit any clinical responses. In addition, two subjects in the study with Ph+ ALL carrying the T315I mutation had either hematologic and/or cytogenetic responses, including one who had a clinical response with a full molecular remission. Six of the nine subjects with MPD having the V617F activating mutation in JAK-2 also had clinical responses. Based on these results, a phase II trial is planned for January of 2007.
December 4, 2006
Cyclacel released positive interim results from a phase I trial of sapacitabine for the treatment of advanced leukemia or myelodysplastic syndromes (MDS). The preliminary data is from 22 subjects. The primary endpoint of this trial was to determine the maximum tolerated dose (MTD) of sapacitabine administered twice daily by mouth for seven consecutive days, every 21 days. One subject receiving a dose level of 275 mg b.i.d. experienced a dose limiting toxicity, which was resolved after treatment ceased. Dose escalation was ongoing at this time with dose limiting toxicities not yet reached at the dose level of 325 mg b.i.d. Cyclacel planned to use these results in the design of a phase II trial expected to commence in 2007.
September 5, 2006
SGX Pharmaceuticals announced negative results from a phase II/III trial of Troxatyl as a third-line treatment for acute myelogenous leukemia (AML). This trial enrolled 211 subjects in the US and Europe. The trial was designed to demonstrate an improvement over the historical data from the M.D. Anderson Cancer Center database, which documented a complete response rate of 4.7% in this patient subgroup. The observed response rates in the Phase II/III trial to date did not show a meaningful improvement over the response rates in the M.D. Anderson Cancer Center historical database. Based on this, a Data Safety Monitoring Board recommended that the trial be discontinued due to lack of evidence that Troxatyl would provide treatment benefit as a third-line treatment for AML. SGX planned to analyze data further in order to determine a future course of action.
April 10, 2006
ArQule issued positive results of a phase I trial of ARQ 501, for the treatment of solid tumors, at the AACR Annual Meeting. Results from the study yielded preliminary efficacy, with tumor regression (2 parital responses, 3 minor responses) or disease stabilization (13 subjects) observed in a number of cancer types, including pancreatic, head and neck, ovarian, and colorectal cancers and leiomyosarcoma. Safety data were also generally positive: serious adverse events included hyperbilirubinemia and dose-limiting hemolytic anemia, but these were transient and clinically manageable. This open-label study enrolled a total of 64 subjects, who received dose-ranging regimens of the drug (10 mg/m2 to 660 mg/m2) via one- or three-hour infusion.
Maxim, through their merger partner EpiCept, announced positive results of a phase III trial of Ceplene for the treatment of AML in the journal Blood. This randomized study enrolled 320 subjects in 11 countries, who received Ceplene plus low dose interleukin-2 or current standard of care (no treatment). Results from the study achieved significance in the primary efficacy endpoint, extending leukemia-free survival at >3 years of follow-up (p=0.0096 in intent-to-treat analysis); the majority of responses were in patients experiencing their first complete remissions (n=261), among whom 3-year leukemia free survival rates were 40% vs. 26% (p=0.01). No treatment-related mortality was observed, and rate of serious adverse events for Ceplene therapy was comparable to the control group.
Sunesis announced positive results of a phase I trial of SNS-595, their napthyridine analog under investigation for the treatment of solid tumors, at the Annual Meeting of the American Association for Cancer Research (AACR). Trial data yielded preliminary evidence of clinical activity, with 28.6% of subjects (n=6/21) achieving sustained disease control through at least 16 weeks; one partial tumor response was noted at the maximum tolerated dose. The drug was shown to be well tolerated: one case of dose-limiting neutropenia was observed, while other adverse events were generally mild. This open-label dose-escalation study enrolled 21 patients with advanced solid tumors. These data were seen to support ongoing phase I (acute leukemias) and phase II (non-small cell and small cell lung cancers) trials of the drug.
January 23, 2006
Breakthrough Therapeutics issued positive interim results of a clinical trial of CMLVAX100, for the treatment of chronic myeloid leukemia (CML). Results of the study indicated that the vaccine was immunogenic in 94% (n=17/18) subjects, producing peptide specific T-cell response. 6 of 10 patients who presented cytogenetic evidence of CML on enrollment experienced complete cytogenic response, and 3 achieved undetectable levels of disease biomarker (bcr-abl transcript). Adverse events were limited to injection-site reactions. This open-label study enrolled 21 patients with stable residual disease following treatment with imatinib, who received 6 vaccinations 2 weeks apart, with additional doses every 4-6 months for positive responders.
GTx has reported positive interim results of a pair of phase III trials of Acapodene (toremifene citrate), for the prevention of prostate cancer, and for the treatment of adverse events associated with androgen deprivation therapy (ADT) for prostate cancer. Preliminary safety data from the fist study were sufficiently positive for the trial's drug safety monitoring board (DSMB) to recommend that the study continue unchanged. Initial results from the second study yielded significant improvements in bone mineral density in the lumbar spine (+2.3%; p<0.001), the hip (+2.0%; p=0.001), and the femur (+1.5%; p=0.009) , vs. placebo. Continuation of the second study was also recommended by its DSMB. The first study enrolled 1,260 men with prostatic intraepithelial neoplasia across 130 sites in the US, Canada, Mexico and Argentina; subjects received 20 mg of the drug or placebo daily. The second study enrolled 1,388 patients on ADT across 150 sites in the US and Mexico, who received 80 mg oral Acapodene or placebo daily.
May 24, 2004
Maxim Pharmaceuticals reported results from a phase III trial investigating Ceplene plus interleukin-2 (IL-2) for the treatment of acute myeloid leukemia (AML). Results showed that subjects treat with Ceplene plus IL-2 experienced a statistically significant increase in leukemia-free survival compared with subjects in the control arm, the studies primary endpoint. The randomized study enrolled 320 subjects with AML in complete remission at multiple sites in North America, Europe, Israel, New Zealand and Australia. Subjects received Ceplene plus IL-2 or the current standard-of-care (no treatment) for at least three years. Significance was assessed by the stratified log-rank test.
April 26, 2004
Bioenvision reported positive interim results from a phase II trial investigating clofarabine, a purine nucleoside analogue for the treatment of with acute myeloid leukemia (AML). Results showed that clofarabine achieved a complete response rate of 64%. The investigator-sponsored study enrolled 18 subjects and was designed to test clofarabine, as first line treatment in older adults with AML considered unsuitable for intensive chemotherapy. Results were reported at the British Society of Hematology meeting in Cardiff, U.K. Clofarabine has demonstrated efficacy in children with relapsed/refractory acute leukemias and in adults with relapsed/refractory AML. Bioenvision plans to begin a European regulatory trial with clofarabine in the same patient population.
August 4, 2003
SuperGen reported positive results from a phase II trial investigating Dacogen (decitabine), a DNA methyltransferase inhibitor for the treatment of chronic myelogenous leukemia. Results showed that 55 subjects achieved an overall objective response, a rate of 43%. There was no significant difference in the response rates among dose levels in the accelerated and blastic phase subjects. Objective response was defined as a complete hematological response, partial hematological response, hematological improvement or a return to the second chronic phase. The study enrolled 130 subjects, most of which were in the blastic or accelerated phase of the disease. Results were published in the August issue of the journal Cancer.
July 14, 2003
EntreMed reported positive results from a phase I trial investigating Panzem (2-Methoxyestradiol (2ME2)), an endogenous estrogen metabolite for the treatment of ovarian cancer. Results showed the drug produced an objective response in one subject with ovarian cancer. The subject demonstrated a 67% reduction in tumor volume and a 78% reduction in the CA125 marker. A maximum tolerated dose was not reached and minimum side effects were reported. The randomized, dose-escalating study enrolled 17 subjects with advanced solid tumors who had an average of six other therapies. The study was conducted by the National Cancer Institute in Bethesda, Maryland. Results were presented at the American Society of Clinical Oncology Annual Meeting in Chicago.<
ILEX Oncology reported positive results from a phase III trial investigating Campath (alemtuzumab), an approved drug, for the first line therapy in subjects with chronic lymphocytic leukemia. Results demonstrated a trend toward longer progression-free survival in subjects taking Campath. Data showed that six subjects achieved molecular remission, which is linked to progression-free survival. The randomized, dose escalating, controlled study enrolled 23 subject who were in remission following first-line therapy with Fludarabine or Fludarabine plus cyclophosphamide. Results were presented at the 2003 Annual Meeting of the American Society of Clinical Oncology.
April 7, 2003
SuperGen reported positive results from a phase II trial investigating Nipent (pentostatin), an injectable antimetabolite for the treatment of chronic lymphocytic leukemia. Results showed there were 17 responses (4 complete and 13 partial) out of 23 subjects for an overall response rate of 74 %. The overall median response duration was 7 months. Subjects achieving complete responses had a median response of 13 months and partial response had a median response of 6 months. Treatment well tolerated with the most common adverse effects reported as mild fatigue and nausea. Serious adverse events included neutropenia, thrombocytopenia and infection. Subjects received six treatment cycles consisting of Nipent and one of two dose levels of cyclophosphamide. The study enrolled 23 subjects with previously treated CLL and was designed to test the efficacy of Nipent in combination with cyclophphamide.
January 27, 2003
Amgen reported positive results from a phase III trial investigating rHu-KGF, a natural keratinocyte growth factor for the treatment of oral mucositis as a complication of cancer treatments. Preliminary results from the randomized, double blind trial were positive on all endpoints showing a highly significant decrease in both the duration and incidence of severe mucositis. In addition, results showed that the drug was well tolerated. The study enrolled subjects who underwent bone marrow transplantation treatment for hematologic malignancies such as lymphoma, multiple myeloma, and leukemia.
December 16, 2002
SuperGen reported positive results from more than 12 trials investigating Nipent for the treatment of multiple cancers. A phase II trial using Nipent in combination with Rituximab for the treatment of chronic lymphocytic leukemia (CLL) demonstrated that 33% of subjects achieved an objective response. Stable disease was observed in 54% of subjects with a median response of 9.8 months. A phase I trial using Nipent for the treatment of steroid refractory acute graft-versus-host disease enrolled 23 subjects with a variety of hematological malignancies. Results showed 11 subjects achieved complete responses and 6 achieved partial or mixed responses. A long term follow-up study of Nipent in 180 subjects with hairy cell leukemia demonstrated a response rate of 98%. Data showed that 83% of subjects achieved a complete response and 15% achieved a partial response.
December 9, 2002
Advanced Magnetics and Cytogen reported positive results from a phase III trial investigating Combidex, an investigational contrast agent for use with magnetic resonance imaging (MRI). The study showed that Combidex is able to distinguish malignant lymph nodes from normal ones in a variety of cancers. In one part of the study, 50 subjects with primary prostate cancer who were scheduled for radical prostatectomy were given an MRI. Using Combidex, the analysis detected malignant lymph nodes with 93% specificity and 92% sensitivity, indicating a high level of correlation. In another part of the study, 12 subjects with renal cancer who were scheduled for radical nephrectomy were given an MRI. Using Combidex, the analysis detected malignant lymph nodes with 86.6% sensitivity and 96.9% specificity, resulting in a positive predictive value of 76.4% and a negative predictive value of 98.4%. Lymph node status is essential for determining the most appropriate strategy in cancer treatment.
Vasogen reported positive results from a phase II trial investigating their immune modulation therapy, an inflammation suppressor for the treatment of chronic lymphocytic leukemia. More than 60% of the treatment subjects in the optimal dose group reached the primary end-point, which was a 25% reduction in total tumor burden or a greater than 25% reduction in lymph node size compared to baseline. The open-label pilot study enrolled 18 subjects with chronic lymphocytic leukemia who were treated in three groups of six subjects each. The study showed the therapy was well tolerated with no treatment related adverse events.
December 2, 2002
Cell Therapeutics reported positive results from a series of clinical trials investigating Trisenox (arsenic trioxide) and concluded that the drug may be effective in inducing high rates of remission in hematologic malignancies like myelodysplasia (MDS) and chronic myeloid leukemia (CML). In the study, 29 subjects with newly diagnosed CML, 19 subjects (66 %) achieved complete remission with four subjects achieving partial remission for an overall response rate of 79 %. In 21 subjects with MDS-refractory anemia (MDS-RA), six subjects (29 %) achieved a complete remission and eight subjects (38 %) achieved a partial remission for an overall objective response rate of 67 %. In 18 subjects with MDS-refractory anemia with excess blasts (MDS-RAEB), three achieved stable disease or better.
Kosan Biosciences and Roche reported positive interim results from a phase I trial investigating KOS-862 (Epothilone D), a polyketide natural product similar to paclitaxel for the treatment of advanced solid tumors. The study is determining possible drug-related toxicities, pharmacokinetics, and pharmacodynamics of escalating intravenous doses of KOS-862 administered every 3 weeks. Pharmacokinetics are linear and the drug shows a 10-hour half-life with good tissue penetration. The pharmacodynamic measurements demonstrate that maximal microtubule bundle formation in peripheral blood cells correlates with maximal plasma concentrations. To date, KOS-862 has been evaluated in 42 subjects with results showing no myelosuppression.