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FDA Approval in Prostate Cancer, NDA Submitted in CLL and Follicular Lymphoma, and More

Gina Columbus
Published: Monday, Feb 12, 2018



Today-

An FDA approval in prostate cancer, a new drug application submitted in CLL and follicular lymphoma, a clinical hold placed on trials of BPX-501, and promising findings in studies of melanoma, non-small cell lung cancer, and multiple myeloma.

Welcome to OncLive News Network! I'm Gina Columbus.

The FDA has approved abiraterone acetate in combination with prednisone for patients with metastatic high-risk castration-sensitive prostate cancer.

The approval was based on data from the phase III LATITUDE trial, in which the addition of abiraterone and prednisone to androgen deprivation therapy compared with ADT alone led to a 38% reduction in the risk of death. After a median follow-up of 30.4 months, median overall survival was not yet reached with abiraterone versus 34.7 months with placebo for patients with high-risk metastatic, castration-sensitive disease.

The median radiographic progression-free survival with abiraterone was 33.0 months versus 14.8 months for ADT alone, representing a 53% reduction in the risk of progression or death. The OS rate at 3 years was 66% in the abiraterone group versus 49% with ADT.

Abiraterone was first approved in 2011 in combination with prednisone for the treatment of men with metastatic castration-resistant prostate cancer following chemotherapy. Since then, it has gained approval earlier in the treatment paradigm for use prior to chemotherapy.

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A new drug application has been submitted to the FDA for duvelisib for a full approval for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma, as well as an accelerated approval for the treatment of patients with relapsed/refractory follicular lymphoma.

The application includes supporting data from both the phase III DUO trial and the phase II DYNAMO study. In DUO, duvelisib reduced the risk of disease progression or death by 48% versus ofatumumab in patients with relapsed/refractory CLL/SLL. In the overall study population, the median progression-free survival with the PI3K-delta and -gamma inhibitor was 3.4 months longer with duvelisib versus ofatumumab.

Also in the overall population, the overall response rate with duvelisib was 73.8% versus 45.3% with ofatumumab, and lymph node burden was reduced by more than half in 85% versus 16% of patients, respectively. In the intent-to-treat population, overall survival between the 2 arms was similar.

In DYNAMO, duvelisib demonstrated an overall response rate of 46% for patients with indolent non-Hodgkin lymphoma, including 41% in patients with follicular lymphoma.

Also in DYNAMO, the ORRs in the follicular lymphoma, SLL, and marginal zone lymphoma subgroups were 41%, 68%, and 33%, respectively. At a median follow-up of 11.5 months, the median overall survival in the entire iNHL population was 18.4 months and the median PFS was 8.4 months.

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The FDA has halted 4 US studies of BPX-501, for cancers and orphan inherited blood disorders, after 3 patients developed encephalopathy possibly related to treatment with the novel cellular immunotherapy.

BPX-501 is an adjunct T-cell therapy administered after allogeneic hematopoietic stem cell transplant, comprising genetically modified donor T cells incorporating Bellicum's CaspaCIDe safety switch. It is designed to provide a safety net to eliminate alloreactive BPX-501 T cells in the event of uncontrollable graft-versus-host disease.

Bellicum Pharmaceuticals, the company manufacturing BPX-501, is currently conducting 4 phase I/II clinical trials of BPX-501 in the United States: BP-001 and BP-005 of BPX-501 in adult patients with hematologic cancers following initial allogeneic HSCT; BP-003, which is in children with orphan inherited blood disorders in which BPX-501 is administered after initial allogeneic HSCT; and BP-008, which includes adults and children with blood cancers to treat post-transplant relapse and evaluate the potential for a titrated dose of rimiducid to resolve uncontrolled GVHD while preserving BPX-501 cells.

In a press release, Bellicum Pharmaceuticals stated that the clinical hold does not affect its European BP-004 trial exploring BPX-501 following initial allogeneic HSCT in children with hematological cancers or orphan inherited blood disorders.

The company added that it has treated more than 240 patients with BPX-501 in 3 allogeneic haploidentical stem cell transplantation studies, and that it is awaiting formal communications from the FDA to determine the requirements for resuming studies.

BPX-501 was granted an orphan drug designation by the FDA in February 2016.

*************************************

In melanoma, updated findings from the COLUMBUS trial demonstrated that combination therapy with encorafenib and binimetinib improved survival versus single-agent vemurafenib in patients with BRAF-mutant advanced, unresectable or metastatic disease.

The phase III data showed that the combination reduced the risk of death by 39% versus vemurafenib monotherapy, and the median overall survival was 33.6 months versus 16.9 months, respectively.

The FDA is currently reviewing a new drug application supporting use of the encorafenib/binimetinib combination in this setting. Under the Prescription Drug User Fee Act, the FDA is scheduled to make its decision by June 30, 2018.

The COLUMBUS trial included 2 parts. In part 1, patients were randomized in a 1:1:1 ratio to receive encorafenib plus binimetinib, encorafenib alone, or twice daily vemurafenib. In part 2, patients were randomized 3:1 to encorafenib plus binimetinib or encorafenib alone.

Across the full study, the median progression-free survival for patients treated with 300-mg encorafenib plus 45-mg binimetinib was 12.9 months compared with 9.2 months for patients receiving encorafenib alone. In those who received a 450-mg dose of encorafenib with 45-mg binimetinib, the median PFS was 14.9 versus 7.3 months with vemurafenib.

******************************

In non-small cell lung cancer, the immunotherapy combination of nivolumab and ipilimumab improved progression-free survival versus chemotherapy in treatment-naïve patients with high tumor mutation burden disease.

The preliminary findings stem from the open-label phase III CheckMate-227 trial. Bristol-Myers Squibb, the manufacturer of both immunotherapies, did not report any further data.

CheckMate-227 is an open-label trial with more than 2500 patients with both nonsquamous and squamous histologies evaluating frontline nivolumab-based regimens versus platinum-doublet chemotherapy in first-line advanced NSCLC that is divided into 3 segments.

In previously reported findings from the phase I CheckMate-012 trial, at a median follow-up of 22 months for nivolumab monotherapy and 16 months for the combination cohorts, the confirmed objective response rate with nivolumab monotherapy was 23% and the median duration of response was not reached. The confirmed ORR in the frontline setting for the combined nivolumab plus ipilimumab cohorts was 43%.

**************************************

The addition of pomalidomide to the combination of bortezomib and low-dose dexamethasone was associated with a significant improvement in progression-free survival in patients with relapsed/refractory myeloma with prior exposure to lenalidomide.

Findings of the phase III OPTIMISMM trial were reported by Celgene, the manufacturer of pomalidomide. The company did not report any additional data but noted that there were no new safety signals and that expanded results would be presented at an upcoming medical meeting.

The international, open-label phase III trial randomized patients with relapsed/refractory disease to the triplet of pomalidomide, bortezomib, and low-dose dexamethasone, or bortezomib and low-dose dexamethasone alone.

The FDA granted an accelerated approval to pomalidomide as a treatment for patients with multiple myeloma following 2 prior therapies, including lenalidomide and bortezomib, in February 2013. This initial approval was based on results from the open-label phase II MM-002 trial. In this analysis, the overall response rate was 7.4% with pomalidomide alone and 29.2% in patients treated with pomalidomide plus low-dose dexamethasone.

**************************************

This week, we sat down with Dr Andrea Cercek, of Memorial Sloan Kettering Cancer Center to discuss early onset colorectal cancer.

That's all for today.

Thank you for watching OncLive News Network! I'm Gina Columbus.
 
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Today-

An FDA approval in prostate cancer, a new drug application submitted in CLL and follicular lymphoma, a clinical hold placed on trials of BPX-501, and promising findings in studies of melanoma, non-small cell lung cancer, and multiple myeloma.

Welcome to OncLive News Network! I'm Gina Columbus.

The FDA has approved abiraterone acetate in combination with prednisone for patients with metastatic high-risk castration-sensitive prostate cancer.

The approval was based on data from the phase III LATITUDE trial, in which the addition of abiraterone and prednisone to androgen deprivation therapy compared with ADT alone led to a 38% reduction in the risk of death. After a median follow-up of 30.4 months, median overall survival was not yet reached with abiraterone versus 34.7 months with placebo for patients with high-risk metastatic, castration-sensitive disease.

The median radiographic progression-free survival with abiraterone was 33.0 months versus 14.8 months for ADT alone, representing a 53% reduction in the risk of progression or death. The OS rate at 3 years was 66% in the abiraterone group versus 49% with ADT.

Abiraterone was first approved in 2011 in combination with prednisone for the treatment of men with metastatic castration-resistant prostate cancer following chemotherapy. Since then, it has gained approval earlier in the treatment paradigm for use prior to chemotherapy.

***************************************

A new drug application has been submitted to the FDA for duvelisib for a full approval for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma, as well as an accelerated approval for the treatment of patients with relapsed/refractory follicular lymphoma.

The application includes supporting data from both the phase III DUO trial and the phase II DYNAMO study. In DUO, duvelisib reduced the risk of disease progression or death by 48% versus ofatumumab in patients with relapsed/refractory CLL/SLL. In the overall study population, the median progression-free survival with the PI3K-delta and -gamma inhibitor was 3.4 months longer with duvelisib versus ofatumumab.

Also in the overall population, the overall response rate with duvelisib was 73.8% versus 45.3% with ofatumumab, and lymph node burden was reduced by more than half in 85% versus 16% of patients, respectively. In the intent-to-treat population, overall survival between the 2 arms was similar.

In DYNAMO, duvelisib demonstrated an overall response rate of 46% for patients with indolent non-Hodgkin lymphoma, including 41% in patients with follicular lymphoma.

Also in DYNAMO, the ORRs in the follicular lymphoma, SLL, and marginal zone lymphoma subgroups were 41%, 68%, and 33%, respectively. At a median follow-up of 11.5 months, the median overall survival in the entire iNHL population was 18.4 months and the median PFS was 8.4 months.

*****************************************

The FDA has halted 4 US studies of BPX-501, for cancers and orphan inherited blood disorders, after 3 patients developed encephalopathy possibly related to treatment with the novel cellular immunotherapy.

BPX-501 is an adjunct T-cell therapy administered after allogeneic hematopoietic stem cell transplant, comprising genetically modified donor T cells incorporating Bellicum's CaspaCIDe safety switch. It is designed to provide a safety net to eliminate alloreactive BPX-501 T cells in the event of uncontrollable graft-versus-host disease.

Bellicum Pharmaceuticals, the company manufacturing BPX-501, is currently conducting 4 phase I/II clinical trials of BPX-501 in the United States: BP-001 and BP-005 of BPX-501 in adult patients with hematologic cancers following initial allogeneic HSCT; BP-003, which is in children with orphan inherited blood disorders in which BPX-501 is administered after initial allogeneic HSCT; and BP-008, which includes adults and children with blood cancers to treat post-transplant relapse and evaluate the potential for a titrated dose of rimiducid to resolve uncontrolled GVHD while preserving BPX-501 cells.

In a press release, Bellicum Pharmaceuticals stated that the clinical hold does not affect its European BP-004 trial exploring BPX-501 following initial allogeneic HSCT in children with hematological cancers or orphan inherited blood disorders.

The company added that it has treated more than 240 patients with BPX-501 in 3 allogeneic haploidentical stem cell transplantation studies, and that it is awaiting formal communications from the FDA to determine the requirements for resuming studies.

BPX-501 was granted an orphan drug designation by the FDA in February 2016.

*************************************

In melanoma, updated findings from the COLUMBUS trial demonstrated that combination therapy with encorafenib and binimetinib improved survival versus single-agent vemurafenib in patients with BRAF-mutant advanced, unresectable or metastatic disease.

The phase III data showed that the combination reduced the risk of death by 39% versus vemurafenib monotherapy, and the median overall survival was 33.6 months versus 16.9 months, respectively.

The FDA is currently reviewing a new drug application supporting use of the encorafenib/binimetinib combination in this setting. Under the Prescription Drug User Fee Act, the FDA is scheduled to make its decision by June 30, 2018.

The COLUMBUS trial included 2 parts. In part 1, patients were randomized in a 1:1:1 ratio to receive encorafenib plus binimetinib, encorafenib alone, or twice daily vemurafenib. In part 2, patients were randomized 3:1 to encorafenib plus binimetinib or encorafenib alone.

Across the full study, the median progression-free survival for patients treated with 300-mg encorafenib plus 45-mg binimetinib was 12.9 months compared with 9.2 months for patients receiving encorafenib alone. In those who received a 450-mg dose of encorafenib with 45-mg binimetinib, the median PFS was 14.9 versus 7.3 months with vemurafenib.

******************************

In non-small cell lung cancer, the immunotherapy combination of nivolumab and ipilimumab improved progression-free survival versus chemotherapy in treatment-naïve patients with high tumor mutation burden disease.

The preliminary findings stem from the open-label phase III CheckMate-227 trial. Bristol-Myers Squibb, the manufacturer of both immunotherapies, did not report any further data.

CheckMate-227 is an open-label trial with more than 2500 patients with both nonsquamous and squamous histologies evaluating frontline nivolumab-based regimens versus platinum-doublet chemotherapy in first-line advanced NSCLC that is divided into 3 segments.

In previously reported findings from the phase I CheckMate-012 trial, at a median follow-up of 22 months for nivolumab monotherapy and 16 months for the combination cohorts, the confirmed objective response rate with nivolumab monotherapy was 23% and the median duration of response was not reached. The confirmed ORR in the frontline setting for the combined nivolumab plus ipilimumab cohorts was 43%.

**************************************

The addition of pomalidomide to the combination of bortezomib and low-dose dexamethasone was associated with a significant improvement in progression-free survival in patients with relapsed/refractory myeloma with prior exposure to lenalidomide.

Findings of the phase III OPTIMISMM trial were reported by Celgene, the manufacturer of pomalidomide. The company did not report any additional data but noted that there were no new safety signals and that expanded results would be presented at an upcoming medical meeting.

The international, open-label phase III trial randomized patients with relapsed/refractory disease to the triplet of pomalidomide, bortezomib, and low-dose dexamethasone, or bortezomib and low-dose dexamethasone alone.

The FDA granted an accelerated approval to pomalidomide as a treatment for patients with multiple myeloma following 2 prior therapies, including lenalidomide and bortezomib, in February 2013. This initial approval was based on results from the open-label phase II MM-002 trial. In this analysis, the overall response rate was 7.4% with pomalidomide alone and 29.2% in patients treated with pomalidomide plus low-dose dexamethasone.

**************************************

This week, we sat down with Dr Andrea Cercek, of Memorial Sloan Kettering Cancer Center to discuss early onset colorectal cancer.

That's all for today.

Thank you for watching OncLive News Network! I'm Gina Columbus.
 
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Community Practice Connections™: Oncology Best Practice™ Decision Points in Advanced NSCLC: Assessing Treatment Options Beyond Disease ProgressionNov 30, 20181.0
Community Practice Connections™: Precision Medicine for Community Oncologists: Assessing the Role of Tumor-Testing Technologies in Cancer CareNov 30, 20181.0
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