December 21, 2015
Spectrum Pharmaceuticals has reported results of a phase I combination trial of belinostat (Beleodaq) with the CHOP (cyclophosphamide, hydroxyl-doxorubicin, Oncovin and Prednisone) chemotherapy regimen as first-line treatment for newly diagnosed peripheral T-cell lymphoma (PTCL). Oncovin is a brand name for vincristine. The open-label, two-part trial enrolled a total of 23 patients. Eleven were enrolled in part A, the dose-escalation phase, to determine the study’s primary endpoint, the maximum tolerated dose (MTD). Part B of the study, the expansion phase, enrolled 12 additional patients at that dose level. The MTD of belinostat was established at 1,000mg/m2 IV infusion on days one through five (the recommended single agent dose) when combined with the CHOP regimen, with each component given at its full recommended dose. Secondary endpoints included safety, tolerability, Objective Response Rate (ORR: complete response + partial response) and pharmacokinetics. Results showed an ORR of 86% with the belinostat and CHOP combination, based on 21 evaluable patients (18/21), with the vast majority, 67%, achieving a complete response (14/21), and 19% achieving a partial response (4/21). In addition, the belinostat and CHOP combination was shown to have an acceptable safety profile with no new or unexpected toxicities. The most common (>10%) grade three/four hematologic adverse events (AEs) reported with Bel-CHOP were as expected: neutrophil count decreased (30%), anemia (22%), neutropenia (22%), white blood cell (WBC) count decreased (22%), febrile neutropenia (17%) and lymphocyte count decreased (17%). No grade three/four non-hematologic AEs >10% were reported. No patient discontinued therapy due to AEs. One patient died as a result of disease progression during the study. Beleodaq is a histone deacetylase (HDAC) inhibitor that received accelerated approval by the FDA for the treatment of relapsed or refractory PTCL in July 2014.
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.
December 15, 2014
Seattle Genetics and Takeda Pharmaceutical
reported results of a phase III study
of Adcetris (brentuximab vedotin) in
Hodgkin lymphoma (HL) patients at risk of
relapse following an autologous stem cell
transplant (ASCT). The randomized, doubleblind,
placebo-controlled study enrolled 329
HL patients, including 165 on the Adcetris
arm and 164 on the placebo arm. Patients
received a median of 15 cycles of treatment
on both arms, with an average of 12 cycles
on the Adcetris arm and 11 cycles on the
placebo arm. The trial demonstrated a
significant increase in PFS per independent
review facility (IRF), with a hazard ratio of 0.57
and a p-value of 0.001. Median PFS per IRF
was 43 months for patients who received Adcetris
v. 24 months for patients who received
placebo. The two-year PFS rate per IRF was
63% in the Adcetris arm compared to 51% in
the placebo arm. The hazard ratio was 0.50.
The two-year PFS rate per investigator was
65% in the Adcetris arm compared to 45%
in the placebo arm. In the Adcetris arm, only
eight of 51 patients (16%) receiving subsequent
therapy were treated with Adcetris
following relapse. In the placebo arm, 72
of 85 patients (85%) receiving subsequent
therapy were treated with single agent Adcetris.
Twenty-four patients in the placebo arm
and 13 patients in the Adcetris arm received
stem cell transplant as subsequent therapy,
the majority of which were allogeneic
transplants. Takeda plans to submit data from
the Aethera trial to regulatory agencies in its
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.
July 22, 2013
Pharmacyclics reported results from a phase II trial of ibrutinib in patients with relapsed/refractory mantle cell lymphoma (MCL). The phase II, open-label, multi-center study enrolled 111 patients internationally; 86% had intermediate or high-risk MCL and had previously undergone treatment with a median of three prior therapies before enrollment in the study. Participants received a 560mg daily oral dose of ibrutinib monotherapy and were treated in two cohorts based on prior exposure to bortezomib—either no prior bortezomib (n=63) or prior bortezomib (n=48). Overall response rate across both cohorts was 68%, with 47% of patients achieving a partial response and 21% achieving a complete response in which all signs of cancer are gone. The estimated median response duration was 17.5 months. The median progression-free survival was 13.9 months and while the median overall survival for this study has not yet been reached, it is estimated to be 58% at 18 months.
July 15, 2013
Pharmacyclics reported results from a phase II studies of ibrutinib for the treatment of relapsed/refractory mantle cell lymphoma (MCL). This multicenter, open-label study treated 111 patients with ibrutinib at 18 sites internationally. Patients were divided into two cohorts based on prior bortezomib exposure—either bortezomib-naïve (n=63) or bortezomibexposed (n=48). Both groups received 560mg of ibrutinib orally, once a day until disease progression or until it was no longer tolerated by the patient. There was an overall response rate (ORR) of 68%, including a complete response (CR) of 21% where all signs of cancer are gone, and a partial response (PR) of 47%. The estimated median duration of response (DOR) in all responding patients was 17.5 months. The median progression-free survival (PFS) was 13.9 months.
July 8, 2013
Affimed Therapeutics released results from a phase I trial of AFM13 for the treatment of advanced relapsing/refractory Hodgkin lymphoma. The 28-patient phase I trial was designed to determine the safety profile, maximum tolerated dose (MTD) and pharmacokinetics (PK), and to provide an indication of activity of AFM13. Twenty-four patients received increasing doses of AFM13 ranging from 0.01mg/kg to 7.0mg/kg on a weekly dosing schedule for four weeks. Four patients were treated with 4.5mg/kg twice a week for four weeks. Thirteen patients received AFM13 at dose levels at and above 1.5mg/kg. The drug showed substantial anti-tumor activity in these patients with eight out of the 13 patients exhibiting a reduction in both tumor volume (as assessed by CT scan) and tumor activity (as assessed by FDG-PET scan imaging). Three out of 13 patients (23%) exhibited a reduction in tumor volume of more than 50%. Data from this phase I trial support further evaluation of AFM13 in relapsing/refractory Hodgkin lymphoma patients.
December 17, 2012
Senesco Technologies released interim results from an ongoing phase Ib/IIa trial of SNS01-T for the treatment of multiple myeloma, mantle cell (MCL) and B-cell lymphoma (DLBCL). This open-label, multiple-dose, dose-escalation study enrolled two patients so far with relapsed or refractory multiple myeloma. Subjects received SNS01-T or 0.0125mg/kg per dose intravenously, while the next three arms will receive SNS01-T or 0.05mg/kg, 0.2mg/kg or 0.375mg/kg per dose intravenously. Blood levels of monoclonal (M)-protein were measured using serum protein electrophoresis. Data showed patients 41-002 and 42-002 in cohort 1, serum levels of M-protein remained within 25% of the baseline values (3.60g/dL, 3.0g/dL respectively) at weeks three (3.90g/dL, 2.8g/dL) and six (4.20g/dL, 2.8g/dL), stable disease. For patient 42-002, M-protein stayed within 25% of baseline at week 10 (3.2g/dL)—four weeks after the end of treatment. M-protein levels for patient 43-001 increased from baseline to week three by 26% and from baseline to week six by 30%. Indicative of the partial disappearance of cancer cells, the plasma cell levels for patients 41-002 and 42-002 declined from 70% to 50% and from 50% to 15%, respectively. Plasma cell levels for patient 43-001 increased from 70% at baseline to 97% at end of treatment. Based on these data, Senesco Technologies will continue to dose patients in the other three arms.
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.
November 1, 2010
4SC AG released positive interim results from a phase II trial of resminostat for the treatment of Hodgkins lymphoma. This open-label, single-arm, Simon two-stage design, dubbed SAPPHIRE, has enrolled 18 subjects with relapsed or refractory disease. The subjects received resminostat 600mg orally daily for five consecutive days, followed by a nine day treatment free period, for up to six treatment cycles. The primary endpoint is to determine the overall response rate (ORR). These data are from the first 18 subjects enrolled in the study. Ten out of the 18 subjects benefited from treatment with resminostat, with two partial responders (more than 50% reduction in size of tumor lesions) and eight subjects with stabilization of disease. This treatment schedule was well tolerated, with the majority of adverse events mild to moderate gastrointestinal and haematological side effects. Based on this data, the trial has proceeded into the 2nd Simon stage recruitment phase. An additional 15 subjects are expected to enroll and will have the option to increase the daily dose of resminostat to 800mg.
October 4, 2010
Seattle Genetics and Millenium issued positive results from a clinical trial evaluating brentuximab vedotin for the treatment of Hodgkin's lymphoma. The single agent trial enrolled 102 subjects with relapsed or refractory Hodgkins lymphoma post-autologous stem cell transplant. The subjects received 1.8 mg/kg of brentuximab vedotin every three weeks for up to 16 total doses. The primary endpoint of the trial was objective response rate. An objective response was reached by 75% of the subjects and the median duration of response was greater than six months. The treatment was determined to be safe and well tolerated.
February 8, 2010
Keryx reported positive results from a phase II trial of perifosine for advanced Waldenstrom's Macroglobulinemia. This open label, single agent trial enrolled 37 subjects with relapsed or refractory disease. The subjects received 150 mg perifosine orally every night for six back to back 28 day cycles. Stable or responding subjects were allowed to continue therapy until progression. Of the 37 subjects, four achieved a partial response (11%), nine achieved a minimal response (24%), and 20 showed stable disease (54%). Overall, 89% of subjects were reported to have stable disease or better, while 11% demonstrated progression. The median progression-free survival was 12.6 months, with a median overall survival of 26 months. Perifosine was generally well-tolerated.
June 9, 2008
Keryx issued positive interim results from a phase II trial of KRX-0401 for the treatment of relapsed/refractory Waldenstroms macroglobulinemia (WM). This study enrolled 37 subjects, most of who had been previously treated with at least one course of therapy on rituximab. The subjects received 150 mg of perifosine daily in a 28 day cycle for at least six cycles. Partial response, defined as a 50 percent reduction in Immunoglobulin M, was observed in 5% of the subjects and minimal response, defined as a 25 percent reduction in Immunoglobulin M, was observed in 28% of the subjects. This resulted in an overall response rate of 33%. An additional 61% of the subjects reached stable disease. Treatment was well tolerated. The median time to progression has not been reached. Eleven subjects are currently receiving treatment.
April 28, 2008
Medarex reported positive results from a phase I/II trial of MDX-060 for the treatment of relapsed or refractory CD30- positive lymphomas. This dose-escalation study enrolled seventy-two subjects who received weekly doses of MDX-060 (0.1, 1, 4, 10 or 15 mg/kg) for four weeks. Of the thirty-three subjects treated at the two highest doses of MDX-060, disease control was observed in 51% (three complete responses, fourteen stable disease). Median progression- free survival was 3.7 months and 39% of subjects showed no evidence of disease progression four months post-treatment. Of the thirty-nine subjects treated at the three lowest doses of MDX-060, disease control was observed in 33% (one complete response, two partial responses, ten stable disease). Median progression-free survival was less than two months and 18% of subjects showed no evidence of disease progression four months post-treatment. MDX-060 treatment was well-tolerated with no clinically meaningful infusion reactions. A phase II trial of MDX-060 is currently underway.
September 10, 2007
Kiadis released positive results from a phase II trial of Reviroc for the treatment of hematological cancers. This non-randomized open label study enrolled 25 subjects with end-stage Non-Hodgkin's lymphoma in Canada. All subjects underwent an autologous graft in bone marrow transplantation using Reviric or a control. The objective of the study was to determine the safety of the Reviroc treatment and its ability to eliminate cancer cells from a contaminated graft. Reviroc was able to eliminate cancer cells from a contaminated graft with out negatively impacting the graft itself. In addition, the Reviroc group had an 80% chance of survival at three years post-transplantation while the control group had a 55% chance of survival. Based on the results, Kiadis is preparing to commence phase III trials.
December 11, 2006
Bayer and Onyx announced negative results from a phase III trial of Nexavar, in combination with carboplatin and paclitaxel, for the treatment of melanoma. This double-blind, randomized, placebo-controlled trial enrolled 270 subjects who received Nexavar or placebo in combination with a standard dosing schedule (21-day cycles) of carboplatin and paclitaxel. The primary endpoint, improvement in progression free survival, was not met with the treatment effect comparable in each arm. Bayer and Onyx plan to continue the development of Nexavar for the potential treatment of various other forms of cancer.
Immunomedics released positive results from a phase II trial of epratuzumab, in combination with rituximab and combined cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (ER-CHOP), for the treatment of diffuse large B-cell lymphoma (DLBCL). This trial enrolled 15 subjects with previously untreated DLBCL who received epratuzumab at 360 mg/m2, followed by rituximab at 375 mg/m2, and a standard dose of CHOP every 3 weeks for 6 to 8 cycles. Treatment was generally well tolerated, although grade 3 or 4 neutropenia observed in 93% of the subjects, or in 28 of 92 cycles (30%), only three subjects developed grade 3 or more infection or fever. Efficacy results revealed that 87% of the subjects responded, including 10 complete responses (67%) and 3 partial responses (20%). At a median follow-up of 30 months, 13 of 15 subjects remained alive. The 1-year progression-free survival (PFS) and overall survival (OS) rates were 93% and 100%, respectively, and the 2-year PFS and OS rates were 86% and 86%, respectively. An additional phase II trial using ER-CHOP is currently underway.
January 30, 2006
Biovest International, a subsidiary of Accentia Biopharmaceuticals, reported follow-up data from a phase II trial of BiovaxID, a personalized anti-tumor vaccine for the treatment of mantle cell lymphoma. Data from the 46 month (3.8-year) follow-up to a phase II study yielded an overall survival rate of 89%; this compared favorably to historical survival rates of 50% at 3 years and 20% at 5 years. Further, BiovaxID induced anti-tumor T-cell lymphocyte responses in most patients, despite B-cell depletion due to chemotherapy. This single-arm, open-label study treated 23 patients with the drug following 6 cycles of EPOCH-R chemotherapy (a regimen which includes rituximab).
September 7, 2004
GenMab announced positive results of their phase II study of HuMax CD-4, their monoclonal antibody for the treatment of cutaneous T-cell lymphoma (CTCL). The trial found that treatment with HuMax CD-4 yielded significant maintained response, with a combined response duration of 6.6 months and a median time to disease progression of 5.7 months across three dosing regimens. Furthermore, subjects receiving one of the two higher doses exhibited longer response, including 6 of the 7 middle dose subjects who maintained the response as of the analysis date. The trial enrolled a total of 38 CTCL patients; early-stage patients received a 560 mg. regimen, while late-stage subjects received either 280 or 980 mg. doses.
June 21, 2004
Medarex reported positive results from a phase II trial investigating MDX-060, a CD30 targeting antibody for the treatment of refractory Hodgkin's disease (HD). Results showed that 18% of subjects (3/17) given MDX-060 (15 mg/kg) experienced an ongoing complete or partial response with a duration of at least three months. All three subjects had failed at least two prior therapies, which included chemotherapy, radiation, immunotherapy and/or autologous stem cell transplant. No infusion reactions or serious drug- related adverse events were reported. The study utilized an expanded cohort from a multi-dose phase I trial enrolling 27 subjects with refractory HD, anaplastic large cell lymphoma or other CD30-positive lymphomas. Subjects received four weekly doses of the MDX-060 antibody at a 10.0 mg/kg or 15.0 mg/kg dose.
January 5, 2004
Genmab reported positive interim results from two phase II trials investigating HuMax-CD4 for the treatment of cutaneous T-cell lymphoma (CTCL). Results showed 55% of the early stage and 38% of the advanced stage subjects achieved at least a partial response, using the Physician's Global Assessment (PGA) scale. The PGA is a comparison of baseline conditions that grades all cancerous lesions from 0 to 6. Data showed that 9% of the early stage and 23% of the advanced stage patients achieved a minor response. In addition, pruritus was improved in 82% of early stage patients and 69% of advanced stage patients. The study enrolled 11 early stage and 13 advanced stage subjects with CTCL.
Introgen reported data from a phase I clinical trial indicating that INGN 241, an MDA-7 gene therapeutic, was well tolerated and was clinically active in subjects with solid tumors. Results showed that the MDA-7 protein was detectable 4 cm away from the injection site. Intratumoral injection of INGN 241 produced protein both in local and diffusible forms. This observation was correlated with apoptosis at the external edge of the tumor that was injected. Results were reported at the 12th Annual International Conference on Gene Therapy of Cancer in San Diego. INGN 241 is currently in phase II clinical trials for the treatment of solid tumors.
Millennium Pharmaceuticals announced positive preliminary results from a phase I/II, investigator-initiated trial with Velcade (bortezomib) in combination with thalidomide with dexamethasone for the treatment of advanced stage multiple myeloma. Of the 56 subjects who are currently enrolled in the trial, 96% received prior autotransplant and 81% received prior thalidomide. Investigators reported that responses were observed in subjects who had previously received thalidomide treatment, and more than 20% of subjects achieved a complete or near complete response. Adverse events included gastrointestinal events, fatigue, peripheral neuropathy and hematologic toxicities. Results were reported at the 45th Annual Meeting of the American Society of Hematology (ASH) in San Diego.
December 15, 2003
Aton Pharma reported positive results from a phase II trial investigating SAHA, a suberoylanilide hydroxamic acid for the treatment of T-cell lymphomas (TCL). Results showed that out of thirteen subjects with refractory or relapsed TCL unresponsive to conventional therapies treated with SAHA, five achieved partial remissions as measured by Physician Global Assessment, five had stable disease and three progressed on therapy. The most commonly reported side effects were dry mouth, change in taste, decreased appetite, nausea, diarrhea and fatigue. Results were presented at the American Society of Hematology 45th Annual Meeting in San Diego.
SuperGen reported results from two multicenter clinical studies with Nipent (pentostatin for injection), for the treatment of non-hodgkin's lymphoma (NHL). The first was a phase II trial that enrolled 60 subjects with previously treated and untreated NHL at 25 sites across the U.S. Results showed that the objective response rate at day 60 was 59.6%, with 12 complete responses and 19 partial responses. In addition, the objective response rate at day 115 was 50.9% with 17 complete responses and 9 partial responses. Subjects received a combination of Nipent and rituximab. The second study was a multi-center pilot trial that enrolled 26 subjects with previously untreated, Stage III or Stage IV low-grade NHL. Results showed there were nine complete responses (37.5%), eight partial responses (33.3%) and four subjects with stable disease (16.7%) for an overall response rate of 83.3%. Subjects received a combination consisting of Nipent, mitoxantrone, and rituximab. Results were presented at the 45th Annual Meeting of the American Society of Hematology (ASH) in San Diego.
February 18, 2003
Abbott Laboratories reported negative preliminary results from a phase III trial investigating atrasentan (ABT-627), an endothelin-blocking protein for the treatment of metastatic prostate cancer. Results showed that the study did not meet its primary endpoint, time-to-disease progression. The endpoint was defined as the need for pain medication, chemotherapy, radiation, and the progression of cancer in bone. The study showed subject dropout rates that were similar to placebo and were lower than in previous studies. Data showed a statistically significant improvement in prostate-specific antigen (PSA) levels compared to placebo (175 ng/ml vs. 257 ng/ml) and improvements in skeletal progression markers. The double blind, placebo-controlled, multinational study enrolled 810 subjects and was designed to examine the effects of atrasentan in men with advanced metastatic hormone-refractory prostate cancer. The company will continue the development of atrasentan in non-metastatic prostate cancer and other cancers.
Transgene reported positive results from two phase I trials investigating their gene therapy products, Adeno Interferon gamma (Ad-IFNg) and Adeno Interleukin-2 (Ad-IL2) for the treatment of various cancers. Both products showed positive results in gene transfer efficiency and cytokine expression. The results also showed positive clinical responses in tumor regression and stabilizations in cutaneous lymphoma subjects treated with Ad-IFNg. The Ad-IFNg trial enrolled 20 subjects with metastatic melanoma or other advanced solid tumors. The Ad-IL2 trial enrolled nine subjects with primary cutaneous T-cell lymphoma and multilesional cutaneous B-cell lymphoma. Treatments were well tolerated in both studies with only mild injection site reactions reported.
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.