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FDA Approval in Melanoma, Priority Reviews in AML and WM, NDAs in Melanoma and SCLC, and More

Gina Columbus
Published: Friday, Jun 29, 2018



Today-

An FDA approval in melanoma, priority review designations in acute myeloid leukemia and Waldenstrom macroglobulinemia, new drug applications accepted in melanoma and non-small cell lung cancer, and additions to immunotherapy labels in bladder cancer.

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

The FDA has approved the combination of the BRAF inhibitor encorafenib and the MEK inhibitor binimetinib, known by the trade names Braftovi and Mektovi, respectively, for the treatment of patients with BRAF-mutant unresectable or metastatic melanoma.

The approval is based on data from the phase III COLUMBUS trial, in which the combination of encorafenib at 450 mg daily and binimetinib at 45 mg twice daily reduced the risk of death by 39% versus vemurafenib monotherapy. At a median follow-up of 36.8 months, the median overall survival was 33.6 months versus 16.9 months, respectively.

Additionally, the 2-year OS rates were 58% versus 43% and the 3-year OS rates were 47% versus 32% with the encorafenib/binimetinib combination versus single-agent vemurafenib, respectively.

The OS benefit with the combination was maintained across all subgroups including those defined by sex, age, BRAF status, LDH level, tumor stage, and number of organs involved at baseline. The COLUMBUS findings also showed a trend toward an OS benefit with the combination versus single-agent encorafenib at 300 mg daily.

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In acute myeloid leukemia, the FDA granted a priority review to a new drug application for glasdegib for use in combination with chemotherapy as a frontline treatment.

The designation is based on data from the phase II BRIGHT 1003 study, in which combining glasdegib with low-dose cytarabine reduced the risk of death by 49.9% versus LDAC alone in treatment-naïve patients with AML or high-risk myelodysplastic syndrome. Results showed that the median overall survival was 8.8 months versus 4.9 months, respectively.

The FDA is scheduled under the Prescription Drug User Fee Act to make its decision on the approval by December 2018.

Moreover, the ongoing phase III BRIGHT AML 1019 trial is exploring glasdegib plus intensive or nonintensive chemotherapy in treatment-naïve patients with AML.

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

The FDA has granted a priority review to a supplemental new drug application for ibrutinib in combination with rituximab as a treatment option across all lines of therapy for patients with Waldenström macroglobulinemia.

The application is based on findings from the randomized phase III iNNOVATE trial. In the study, the combination lowered the risk of disease progression or death by 80% versus rituximab alone in patients with Waldenström macroglobulinemia.

At a median follow-up of 26.5 months, the median progression-free survival was not reached with the ibrutinib combination and was 20.3 months with rituximab alone. The 30-months PFS rates were 82% versus 28%, respectively.

The PFS benefit with the combination was observed across key subgroups. Moreover, the ORR in the overall population was 92% with the ibrutinib combination versus 47% with rituximab alone. The major response rate was 72% versus 32%, respectively.

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

In melanoma, the FDA has accepted a supplemental biologics license application for the use of pembrolizumab as an adjuvant treatment for patients with resected, high-risk stage III disease.

The application is supported by data from the phase III EORTC 1325-MG/KEYNOTE-054 trial. In the study, adjuvant pembrolizumab was found to reduce the risk of recurrence or death by 43% in patients with resected, high-risk stage III melanoma.

At a median follow-up of 15 months, the 1-year recurrence-free survival rate was 75.4% with the PD-1 inhibitor versus 61.0% with placebo. The RFS benefit was observed regardless of PD-L1 or BRAF mutation status. The FDA is scheduled to make its decision on the application by February 16, 2019.

Additionally, the 18-month relapse-free survival rate was 71.4% with pembrolizumab versus 53.2% with placebo. This benefit with pembrolizumab was observed across patients with either stage IIIA, IIIB, or IIIC disease.

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

The FDA has also accepted a supplemental biologics license application or the combination of nivolumab plus ipilimumab for the frontline treatment of patients with advanced non-small cell lung cancer. The indication would be specifically for patients with tumor mutational burden more than 10 mutations per megabase.

The application is based on findings from the phase III CheckMate-227 trial, in which the 1-year progression-free survival rate was 43% for patients with high TMB assigned to the immunotherapy combination versus 13% for those assigned to platinum-doublet chemotherapy. The median PFS was 7.2 months versus 5.5 months, respectively, representing a 42% reduction in the risk of disease progression or death.

The combination was well tolerated, and safety was similar to previous results with the therapies. The rate of grade 3/4 treatment-related adverse events was 31% in the immunotherapy combination arm versus 36% with chemotherapy.

A final decision on the application is expected by February 20, 2019.

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

The FDA has incorporated PD-L1 status into the labels for pembrolizumab and atezolizumab for existing frontline approvals for cisplatin-ineligible patients with urothelial carcinoma. This decision stems from lower overall survival rates with the PD-1/PD-L1 inhibitors versus platinum-based chemotherapy for patients with PD-L1–low expressing platinum-eligible disease.

The FDA decision was based on an assessment conducted by a data monitoring committee for the phase III KEYNOTE-361 study with pembrolizumab and the phase III IMvigor130 study with atezolizumab. The KEYNOTE-361 and the IMvigor130 studies are exploring the checkpoint inhibitors with or without chemotherapy versus chemotherapy or the immunotherapy alone.

The data monitoring committee identified that patients with PD-L1–low status had decreased overall survival in the single-agent immunotherapy arms compared with chemotherapy. Both trials have stopped enrolling patients with PD-L1–low status to the monotherapy arms. However, other arms of the trials will remain open to patients, regardless of PD-L1 status.

Several clinical trials exploring checkpoint inhibitors remain ongoing for patients with urothelial carcinoma.

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

This week, we sat down with Dr Wells Messersmith of University of Colorado Cancer Center to discuss key investigations in advanced 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 melanoma, priority review designations in acute myeloid leukemia and Waldenstrom macroglobulinemia, new drug applications accepted in melanoma and non-small cell lung cancer, and additions to immunotherapy labels in bladder cancer.

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

The FDA has approved the combination of the BRAF inhibitor encorafenib and the MEK inhibitor binimetinib, known by the trade names Braftovi and Mektovi, respectively, for the treatment of patients with BRAF-mutant unresectable or metastatic melanoma.

The approval is based on data from the phase III COLUMBUS trial, in which the combination of encorafenib at 450 mg daily and binimetinib at 45 mg twice daily reduced the risk of death by 39% versus vemurafenib monotherapy. At a median follow-up of 36.8 months, the median overall survival was 33.6 months versus 16.9 months, respectively.

Additionally, the 2-year OS rates were 58% versus 43% and the 3-year OS rates were 47% versus 32% with the encorafenib/binimetinib combination versus single-agent vemurafenib, respectively.

The OS benefit with the combination was maintained across all subgroups including those defined by sex, age, BRAF status, LDH level, tumor stage, and number of organs involved at baseline. The COLUMBUS findings also showed a trend toward an OS benefit with the combination versus single-agent encorafenib at 300 mg daily.

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

In acute myeloid leukemia, the FDA granted a priority review to a new drug application for glasdegib for use in combination with chemotherapy as a frontline treatment.

The designation is based on data from the phase II BRIGHT 1003 study, in which combining glasdegib with low-dose cytarabine reduced the risk of death by 49.9% versus LDAC alone in treatment-naïve patients with AML or high-risk myelodysplastic syndrome. Results showed that the median overall survival was 8.8 months versus 4.9 months, respectively.

The FDA is scheduled under the Prescription Drug User Fee Act to make its decision on the approval by December 2018.

Moreover, the ongoing phase III BRIGHT AML 1019 trial is exploring glasdegib plus intensive or nonintensive chemotherapy in treatment-naïve patients with AML.

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

The FDA has granted a priority review to a supplemental new drug application for ibrutinib in combination with rituximab as a treatment option across all lines of therapy for patients with Waldenström macroglobulinemia.

The application is based on findings from the randomized phase III iNNOVATE trial. In the study, the combination lowered the risk of disease progression or death by 80% versus rituximab alone in patients with Waldenström macroglobulinemia.

At a median follow-up of 26.5 months, the median progression-free survival was not reached with the ibrutinib combination and was 20.3 months with rituximab alone. The 30-months PFS rates were 82% versus 28%, respectively.

The PFS benefit with the combination was observed across key subgroups. Moreover, the ORR in the overall population was 92% with the ibrutinib combination versus 47% with rituximab alone. The major response rate was 72% versus 32%, respectively.

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

In melanoma, the FDA has accepted a supplemental biologics license application for the use of pembrolizumab as an adjuvant treatment for patients with resected, high-risk stage III disease.

The application is supported by data from the phase III EORTC 1325-MG/KEYNOTE-054 trial. In the study, adjuvant pembrolizumab was found to reduce the risk of recurrence or death by 43% in patients with resected, high-risk stage III melanoma.

At a median follow-up of 15 months, the 1-year recurrence-free survival rate was 75.4% with the PD-1 inhibitor versus 61.0% with placebo. The RFS benefit was observed regardless of PD-L1 or BRAF mutation status. The FDA is scheduled to make its decision on the application by February 16, 2019.

Additionally, the 18-month relapse-free survival rate was 71.4% with pembrolizumab versus 53.2% with placebo. This benefit with pembrolizumab was observed across patients with either stage IIIA, IIIB, or IIIC disease.

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

The FDA has also accepted a supplemental biologics license application or the combination of nivolumab plus ipilimumab for the frontline treatment of patients with advanced non-small cell lung cancer. The indication would be specifically for patients with tumor mutational burden more than 10 mutations per megabase.

The application is based on findings from the phase III CheckMate-227 trial, in which the 1-year progression-free survival rate was 43% for patients with high TMB assigned to the immunotherapy combination versus 13% for those assigned to platinum-doublet chemotherapy. The median PFS was 7.2 months versus 5.5 months, respectively, representing a 42% reduction in the risk of disease progression or death.

The combination was well tolerated, and safety was similar to previous results with the therapies. The rate of grade 3/4 treatment-related adverse events was 31% in the immunotherapy combination arm versus 36% with chemotherapy.

A final decision on the application is expected by February 20, 2019.

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

The FDA has incorporated PD-L1 status into the labels for pembrolizumab and atezolizumab for existing frontline approvals for cisplatin-ineligible patients with urothelial carcinoma. This decision stems from lower overall survival rates with the PD-1/PD-L1 inhibitors versus platinum-based chemotherapy for patients with PD-L1–low expressing platinum-eligible disease.

The FDA decision was based on an assessment conducted by a data monitoring committee for the phase III KEYNOTE-361 study with pembrolizumab and the phase III IMvigor130 study with atezolizumab. The KEYNOTE-361 and the IMvigor130 studies are exploring the checkpoint inhibitors with or without chemotherapy versus chemotherapy or the immunotherapy alone.

The data monitoring committee identified that patients with PD-L1–low status had decreased overall survival in the single-agent immunotherapy arms compared with chemotherapy. Both trials have stopped enrolling patients with PD-L1–low status to the monotherapy arms. However, other arms of the trials will remain open to patients, regardless of PD-L1 status.

Several clinical trials exploring checkpoint inhibitors remain ongoing for patients with urothelial carcinoma.

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

This week, we sat down with Dr Wells Messersmith of University of Colorado Cancer Center to discuss key investigations in advanced colorectal cancer.

That’s all for today.

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