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Breakthrough Therapy Designation in CSCC, BLA for a Biosimilar, 2017 ESMO Congress Highlights, and More

Gina Columbus
Published: Saturday, Sep 16, 2017



Today-

A breakthrough therapy designation in cutaneous squamous cell carcinoma, a biologics license application for a biosimilar, clinical holds placed on trials in multiple myeloma and other hematologic malignancies, and highlights from the 2017 ESMO Congress.

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

The FDA has granted a breakthrough therapy designation to the anti–PD-1 agent cemiplimab for the treatment of adults with metastatic cutaneous squamous cell carcinoma and adults with locally advanced and unresectable CSCC. 

CSCC is the second most common and second deadliest type of skin cancer in the United States, behind only melanoma. 

Regneron, the manufacturer of cemiplimab, submitted preliminary results from 2 expansion cohorts of a phase I study involving 26 patients with advanced CSCC at the 2017 ASCO Annual Meeting. Regneron submitted data from this study to the FDA in support of cemiplimab.

Results showed the investigator assessed preliminary overall response rate was 46.2%. Two patients with locally advanced disease had a complete response. Ten patients had a partial response, including 1 unconfirmed partial complete response. A total of 6 patients had stable disease and 6 others had progressive disease. The disease control rate was 69.2%.

The breakthrough therapy designation accelerates the development and review of drugs targeting serious or life-threatening conditions. Drugs qualifying for this designation must show credible evidence of a substantial improvement on a clinically significant endpoint over available therapies, or over placebo if there is no available therapy.

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

The FDA has accepted a biologics license application for the rituximab biosimilar Rixathon.

If approved, Rixathon would be indicated for the hematologic malignancies follicular lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia, as well as for rheumatoid arthritis. The European Commission approved Rixathon to be marketed for these indications in the EU in June 2017.

The application is based on a series of data, including results from the ASSIST-RA study in rheumatoid arthritis and the phase III confirmatory ASSIST-FL study in follicular lymphoma.

In ASSIST-FL, which explored the biosimilar in untreated patients with advanced stage follicular lymphoma, the overall response rate was 87.1% in the Rixathon/cyclophosphamide, vincristine, prednisone arm versus 87.5% in the rituximab-CVP arm.

The rate of complete response was 14.8% and the partial response rate was the 72.3% in the Rixathon arm. The complete response rate was 13.4% with a partial response rate of 74.1% in the rituximab-CVP group. The median progression-free survival and overall survival had not been reached.

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

The FDA has placed partial clinical holds on 3 trials assessing nivolumab-based combinations in patients with relapsed/refractory multiple myeloma.

The phase III CheckMate-602, phase I CheckMate-039, and phase II CA204142 are all affected by the decision. Enrolled patients who are experiencing clinical benefit can continue treatment, but no new patients will be allowed to join the trials for the time being.

Bristol-Myers Squibb, the manufacturer of nivolumab, noted in a press release that other studies of nivolumab outside of multiple myeloma will continue as planned.

The FDA made the move based on safety concerns identified in 2 clinical trials evaluating another anti–PD-1 agent, pembrolizumab, in combination with dexamethasone and lenalidomide or pomalidomide for the treatment of patients with multiple myeloma.

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

The FDA has also placed clinical holds on multiple trials in Celgene’s FUSION program, which is exploring regimens combining durvalumab with immunomodulatory and chemotherapy agents across several hematologic malignancies.

The agency has stopped 1 trial and put partial holds on 5 others due to the safety concerns that arose in pembrolizumab combination studies with immunomodulatory agents in patients with multiple myeloma.

The FDA placed a full hold on the phase IB multicenter trial MEDI4736-MM-002, which was designed to establish an appropriate dose and regimen for the combination of durvalumab and lenalidomide with and without low-dose dexamethasone in patients with newly diagnosed multiple myeloma. No new patients will be enrolled and those in that trial will discontinue treatment.

Three studies exploring durvalumab in multiple myeloma were placed on a partial hold. These include MEDI4736-MM-001, MEDI4736-MM-003, and MEDI4736-MM-005.

MEDI4736-NHL-001, which is exploring durvalumab as a monotherapy in patients with lymphoma or chronic lymphocytic leukemia, and MEDI4736-DLBCL-001, which is assessing durvalumab in combination with R-CHOP or R2 CHOP, were also put on a partial hold.

Celgene reported in a press release that it has not determined whether the benefits associated with durvalumab in these settings exceed the risks, but the clinical holds allow for additional information to be collected to further understand the risk-benefit profile of the program.

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

Exciting research was presented at the 2017 ESMO Congress in Madrid Spain, this past week, highlighting advancements across tumor types, including lung cancer, breast cancer, melanoma, and genitourinary malignancies.

In lung cancer, the PD-L1 inhibitor durvalumab was found to improve progression-free survival by 11.2 months versus placebo for patients with locally advanced, unresectable stage III NSCLC who had not progressed following chemoradiotherapy, according to phase III results from the PACIFIC trial.

At 12 months, 55.9% of those in the durvalumab arm remained progression free compared with 35.3% with placebo. The 18-month PFS rates were 44.2% and 27.0%, for durvalumab and placebo, respectively. Additionally, an analysis of overall survival had not yet been conducted; this endpoint remained blinded. 

Also in NSCLC, phase III results from the FLAURA trial showed that frontline osimertinib improved the median progression-free survival by 18.9 months, representing a 54% reduction in the risk of progression or death versus standard therapy for patients with EGFR-mutant disease.

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

In breast cancer, adding abemaciclib to anastrozole or letrozole reduced the risk of progression or death by 46% versus non-steroidal aromatase inhibitor alone for previously untreated patients with HER2-negative, HR-positive advanced breast cancer.

In the phase III MONARCH3 study, which was presented at ESMO, the median progression-free survival was not yet reached in the abemaciclib arm versus 14.7 months with the NSAI alone. In those with measurable disease, the objective response rate was 59.2% with the CDK 4/6 inhibitor and 43.8% in the control arm.

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

In melanoma news out of ESMO, findings from the phase III COMBI-AD trial demonstrated that adjuvant treatment with dabrafenib and trametinib reduced the risk of relapse or death by 53% compared with placebo for patients with BRAF-mutant stage III melanoma.

After a median follow-up of 2.8 years, the 3-year relapse-free survival rate with dabrafenib and trametinib was 58% versus 39% for placebo. Early data for overall survival showed that 86% of patients in the combination arm were alive at 3 years versus 77% with placebo. The interim analysis showed that the overall survival advantage was not yet deemed statistically significant.

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

In genitourinary malignancies, frontline treatment with the combination of nivolumab and ipilimumab reduced the risk of death by 32% compared with sunitinib for patients with metastatic renal cell carcinoma, according to findings from the CheckMate 214 study presented at ESMO.

Results showed that the median overall survival was not reached with the combination versus 32.9 months with sunitinib. Moreover, the median OS was not reached in the nivolumab and ipilimumab arm and was 26.0 months in the sunitinib arm, representing a 37% reduction in the risk of death, in patients with intermediate- and poor-risk RCC.

Based on the improvement in OS, Bristol-Myers Squibb, the company developing the combination, announced that the trial had been stopped to allow patients to cross over from the sunitinib arm. BMS plans to submit the findings to regulatory authorities for potential approval.

And finally, mature results from the phase III KEYNOTE-045 study presented at ESMO demonstrated that overall survival with pembrolizumab continued to improve versus chemotherapy in patients with recurrent, advanced urothelial carcinoma.

The median OS was significantly longer with pembrolizumab compared with chemotherapy in the overall patient population, at 10.3 versus 7.4 months, respectively.

Additionally, significantly improved OS was observed regardless of the level of PD-L1 expression. The 18-month OS rates were 33.2% compared to 19.7% with pembrolizumab versus chemotherapy, respectively.

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

This week, we sat down with Dr Omid Hamid of The Angeles Clinic and Research Institute, to discuss the phase I/II results of the ECHO-202/KEYNOTE-037 trial, which explored the IDO inhibitor epacadostat plus pembrolizumab in patients with advanced melanoma.

That’s all for today.

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

A breakthrough therapy designation in cutaneous squamous cell carcinoma, a biologics license application for a biosimilar, clinical holds placed on trials in multiple myeloma and other hematologic malignancies, and highlights from the 2017 ESMO Congress.

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

The FDA has granted a breakthrough therapy designation to the anti–PD-1 agent cemiplimab for the treatment of adults with metastatic cutaneous squamous cell carcinoma and adults with locally advanced and unresectable CSCC. 

CSCC is the second most common and second deadliest type of skin cancer in the United States, behind only melanoma. 

Regneron, the manufacturer of cemiplimab, submitted preliminary results from 2 expansion cohorts of a phase I study involving 26 patients with advanced CSCC at the 2017 ASCO Annual Meeting. Regneron submitted data from this study to the FDA in support of cemiplimab.

Results showed the investigator assessed preliminary overall response rate was 46.2%. Two patients with locally advanced disease had a complete response. Ten patients had a partial response, including 1 unconfirmed partial complete response. A total of 6 patients had stable disease and 6 others had progressive disease. The disease control rate was 69.2%.

The breakthrough therapy designation accelerates the development and review of drugs targeting serious or life-threatening conditions. Drugs qualifying for this designation must show credible evidence of a substantial improvement on a clinically significant endpoint over available therapies, or over placebo if there is no available therapy.

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

The FDA has accepted a biologics license application for the rituximab biosimilar Rixathon.

If approved, Rixathon would be indicated for the hematologic malignancies follicular lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia, as well as for rheumatoid arthritis. The European Commission approved Rixathon to be marketed for these indications in the EU in June 2017.

The application is based on a series of data, including results from the ASSIST-RA study in rheumatoid arthritis and the phase III confirmatory ASSIST-FL study in follicular lymphoma.

In ASSIST-FL, which explored the biosimilar in untreated patients with advanced stage follicular lymphoma, the overall response rate was 87.1% in the Rixathon/cyclophosphamide, vincristine, prednisone arm versus 87.5% in the rituximab-CVP arm.

The rate of complete response was 14.8% and the partial response rate was the 72.3% in the Rixathon arm. The complete response rate was 13.4% with a partial response rate of 74.1% in the rituximab-CVP group. The median progression-free survival and overall survival had not been reached.

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

The FDA has placed partial clinical holds on 3 trials assessing nivolumab-based combinations in patients with relapsed/refractory multiple myeloma.

The phase III CheckMate-602, phase I CheckMate-039, and phase II CA204142 are all affected by the decision. Enrolled patients who are experiencing clinical benefit can continue treatment, but no new patients will be allowed to join the trials for the time being.

Bristol-Myers Squibb, the manufacturer of nivolumab, noted in a press release that other studies of nivolumab outside of multiple myeloma will continue as planned.

The FDA made the move based on safety concerns identified in 2 clinical trials evaluating another anti–PD-1 agent, pembrolizumab, in combination with dexamethasone and lenalidomide or pomalidomide for the treatment of patients with multiple myeloma.

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

The FDA has also placed clinical holds on multiple trials in Celgene’s FUSION program, which is exploring regimens combining durvalumab with immunomodulatory and chemotherapy agents across several hematologic malignancies.

The agency has stopped 1 trial and put partial holds on 5 others due to the safety concerns that arose in pembrolizumab combination studies with immunomodulatory agents in patients with multiple myeloma.

The FDA placed a full hold on the phase IB multicenter trial MEDI4736-MM-002, which was designed to establish an appropriate dose and regimen for the combination of durvalumab and lenalidomide with and without low-dose dexamethasone in patients with newly diagnosed multiple myeloma. No new patients will be enrolled and those in that trial will discontinue treatment.

Three studies exploring durvalumab in multiple myeloma were placed on a partial hold. These include MEDI4736-MM-001, MEDI4736-MM-003, and MEDI4736-MM-005.

MEDI4736-NHL-001, which is exploring durvalumab as a monotherapy in patients with lymphoma or chronic lymphocytic leukemia, and MEDI4736-DLBCL-001, which is assessing durvalumab in combination with R-CHOP or R2 CHOP, were also put on a partial hold.

Celgene reported in a press release that it has not determined whether the benefits associated with durvalumab in these settings exceed the risks, but the clinical holds allow for additional information to be collected to further understand the risk-benefit profile of the program.

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

Exciting research was presented at the 2017 ESMO Congress in Madrid Spain, this past week, highlighting advancements across tumor types, including lung cancer, breast cancer, melanoma, and genitourinary malignancies.

In lung cancer, the PD-L1 inhibitor durvalumab was found to improve progression-free survival by 11.2 months versus placebo for patients with locally advanced, unresectable stage III NSCLC who had not progressed following chemoradiotherapy, according to phase III results from the PACIFIC trial.

At 12 months, 55.9% of those in the durvalumab arm remained progression free compared with 35.3% with placebo. The 18-month PFS rates were 44.2% and 27.0%, for durvalumab and placebo, respectively. Additionally, an analysis of overall survival had not yet been conducted; this endpoint remained blinded. 

Also in NSCLC, phase III results from the FLAURA trial showed that frontline osimertinib improved the median progression-free survival by 18.9 months, representing a 54% reduction in the risk of progression or death versus standard therapy for patients with EGFR-mutant disease.

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

In breast cancer, adding abemaciclib to anastrozole or letrozole reduced the risk of progression or death by 46% versus non-steroidal aromatase inhibitor alone for previously untreated patients with HER2-negative, HR-positive advanced breast cancer.

In the phase III MONARCH3 study, which was presented at ESMO, the median progression-free survival was not yet reached in the abemaciclib arm versus 14.7 months with the NSAI alone. In those with measurable disease, the objective response rate was 59.2% with the CDK 4/6 inhibitor and 43.8% in the control arm.

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

In melanoma news out of ESMO, findings from the phase III COMBI-AD trial demonstrated that adjuvant treatment with dabrafenib and trametinib reduced the risk of relapse or death by 53% compared with placebo for patients with BRAF-mutant stage III melanoma.

After a median follow-up of 2.8 years, the 3-year relapse-free survival rate with dabrafenib and trametinib was 58% versus 39% for placebo. Early data for overall survival showed that 86% of patients in the combination arm were alive at 3 years versus 77% with placebo. The interim analysis showed that the overall survival advantage was not yet deemed statistically significant.

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

In genitourinary malignancies, frontline treatment with the combination of nivolumab and ipilimumab reduced the risk of death by 32% compared with sunitinib for patients with metastatic renal cell carcinoma, according to findings from the CheckMate 214 study presented at ESMO.

Results showed that the median overall survival was not reached with the combination versus 32.9 months with sunitinib. Moreover, the median OS was not reached in the nivolumab and ipilimumab arm and was 26.0 months in the sunitinib arm, representing a 37% reduction in the risk of death, in patients with intermediate- and poor-risk RCC.

Based on the improvement in OS, Bristol-Myers Squibb, the company developing the combination, announced that the trial had been stopped to allow patients to cross over from the sunitinib arm. BMS plans to submit the findings to regulatory authorities for potential approval.

And finally, mature results from the phase III KEYNOTE-045 study presented at ESMO demonstrated that overall survival with pembrolizumab continued to improve versus chemotherapy in patients with recurrent, advanced urothelial carcinoma.

The median OS was significantly longer with pembrolizumab compared with chemotherapy in the overall patient population, at 10.3 versus 7.4 months, respectively.

Additionally, significantly improved OS was observed regardless of the level of PD-L1 expression. The 18-month OS rates were 33.2% compared to 19.7% with pembrolizumab versus chemotherapy, respectively.

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

This week, we sat down with Dr Omid Hamid of The Angeles Clinic and Research Institute, to discuss the phase I/II results of the ECHO-202/KEYNOTE-037 trial, which explored the IDO inhibitor epacadostat plus pembrolizumab in patients with advanced melanoma.

That’s all for today.

Thank you for watching OncLive News Network! I’m Gina Columbus.
 
View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: CDK4/6 Inhibitors With the Experts: The Role of Emerging Agents for the Management of Metastatic Breast CancerMay 30, 20182.0
Medical Crossfire®: Clinical Updates on PARP Inhibition and its Evolving Use in the Treatment of CancersMay 30, 20181.5
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