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FDA Approvals in Large B-Cell Lymphoma and Melanoma, Priority Reviews in CSCC and NSCLC, and More

Gina Columbus
Published: Friday, May 04, 2018



Today-

FDA approvals in large B-cell lymphoma and melanoma, priority review designations in cutaneous squamous cell carcinoma and non-small cell lung cancer, a new drug application submitted in acute myeloid leukemia, and a European approval for a new PD-1 inhibitor dosing schedule.

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

The FDA has approved the chimeric antigen receptor therapy tisagenlecleucel for use in adult patients with relapsed/refractory large B-cell lymphoma, including diffuse large B-cell lymphoma, high-grade B-cell lymphoma and DLBCL arising from follicular lymphoma after 2 or more lines of systemic therapy.

The approval is based on findings from the phase II JULIET study, in which the CD19-directed CAR T-cell product reached an overall response rate of 50% in adult patients with relapsed/refractory DLBCL. Moreover, the complete response rate was 32% and the partial response rate was 18%. The median duration of response had not been reached.

Regarding safety, all-grade adverse events occurring in at least 20% of the 106 infused patients included cytokine release syndrome, infections, pyrexia, diarrhea, nausea, fatigue, hypotension, edema, and headache.

Tisagenlecleucel became the first CAR T-cell therapy approved by the FDA in August 2017, when the agency authorized the treatment’s use for patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia that is refractory or in second or later relapse.

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

In melanoma, the FDA approved the combination of dabrafenib and trametinib for the adjuvant treatment of patients with BRAF V600E– or V600K–positive stage III melanoma following complete resection.

The approval is based on data from the phase III COMBI-AD study, in which adjuvant treatment with dabrafenib and trametinib reduced the risk of relapse or death by 53% versus placebo for patients with BRAF-mutant stage III disease.

Additionally, 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.

The median RFS was not reached with the combination versus 16.6 months for placebo and RFS was improved with dabrafenib/trametinib across all subgroups. Overall hazard ratios ranged from 0.33 to 0.55 in favor of the combination versus placebo.

Early data for overall survival showed that 86% of patients in the combination arm were alive at 3 years versus 77% with placebo. At an interim analysis, the OS advantage was not yet deemed statistically significant.

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

The FDA has granted a priority review to a biologics license application for cemiplimab as a treatment for patients with metastatic cutaneous squamous cell carcinoma or those with locally advanced CSCC who are ineligible for surgery.

The submitted application was based on results from the phase II EMPOWER-CSCC 1 study, in which the overall response rate was 46.3% in patients with advanced CSCC. Regeneron and Sanofi, the codevelopers of cemiplimab, also submitted supporting data from 2 phase I expansion cohorts of patients with advanced disease. Updated data from these phase I and II studies will be presented at the 2018 ASCO Annual Meeting.

Phase I data for cemiplimab in advanced CSCC, which were reported at the 2017 ASCO Annual Meeting, demonstrated a disease control rate of 69.2%.

Cemiplimab previously received an FDA breakthrough therapy designation in CSCC. The FDA is scheduled to make its decision on the application by October 28, 2018.

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

In non-small cell lung cancer, the FDA has granted a priority review to a supplemental biologics license application for frontline pembrolizumab combined with chemotherapy for patients with metastatic nonsquamous disease.

The application is based on the phase III KEYNOTE-189 trial, in which the addition of pembrolizumab to pemetrexed and either cisplatin or carboplatin in the first-line setting reduced the risk of death by more than 50% in patients with NSCLC without EGFR or ALK mutations.

KEYNOTE-189 is the confirmatory trial to convert the accelerated approval of this regimen into a full approval.

In the study, at a median follow-up of 10.5 months, the estimated 12-month overall survival rate was 69.2% in the pembrolizumab arm versus 49.4% in the control group. The median OS was not reached in the pembrolizumab cohort, compared with 11.3 months in the chemotherapy-alone arm. The OS benefit was observed, irrespective of PD-L1 status.

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

A new drug application for gilteritinib has been submitted to the FDA for the treatment of adult patients with FLT3 mutation–positive relapsed or refractory acute myeloid leukemia.

The NDA is based on data from the ongoing phase III ADMIRAL study, which is evaluating gilteritinib versus salvage chemotherapy in adult patients with FLT3-positive relapse/refractory AML. Astellas Pharma, the developer of gilteritinib, has also submitted an application to Japanese regulatory authorities for marketing approval for the FLT3 inhibitor in the same setting.

Data from the open-label, multicenter ADMIRAL trial have not yet been made available. The coprimary endpoints are overall survival and complete remission or CR with partial hematological recovery.

In October 2017, the FDA granted fast track designation to gilteritinib for adult patients with FLT3 mutation-positive relapsed/refractory AML.

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

In Europe, a 4-week dosing schedule for nivolumab has been approved by the European Commission for the treatment of patients with advanced melanoma and previously treated renal cell carcinoma.

The commission specifically approved a 4-week dosing regimen with 480 mg of nivolumab for these indications. Additionally, the EU approved replacing weight-based dosing with 240 mg every 2 weeks for the 6 nivolumab monotherapy indications approved in the European Union, which are melanoma, non–small cell lung cancer, RCC, classical Hodgkin lymphoma, head and neck squamous cell carcinoma, and urothelial carcinoma.

In March 2018, the FDA approved a supplemental biologics license application adding the 4-week dosing schedule for nivolumab across several of the PD-1 inhibitor’s indications. Physicians now have the option of using either the new 4-week dosing schedule or the previously approved schedule of 240 mg every 2 weeks, now available in a new 240 mg vial.

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

This week, we sat down with Dr Anas Younes of Memorial Sloan Kettering Cancer Center, to discuss initial steps for treatment of patients with diffuse large B-cell lymphoma.

That’s all for today.

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

FDA approvals in large B-cell lymphoma and melanoma, priority review designations in cutaneous squamous cell carcinoma and non-small cell lung cancer, a new drug application submitted in acute myeloid leukemia, and a European approval for a new PD-1 inhibitor dosing schedule.

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

The FDA has approved the chimeric antigen receptor therapy tisagenlecleucel for use in adult patients with relapsed/refractory large B-cell lymphoma, including diffuse large B-cell lymphoma, high-grade B-cell lymphoma and DLBCL arising from follicular lymphoma after 2 or more lines of systemic therapy.

The approval is based on findings from the phase II JULIET study, in which the CD19-directed CAR T-cell product reached an overall response rate of 50% in adult patients with relapsed/refractory DLBCL. Moreover, the complete response rate was 32% and the partial response rate was 18%. The median duration of response had not been reached.

Regarding safety, all-grade adverse events occurring in at least 20% of the 106 infused patients included cytokine release syndrome, infections, pyrexia, diarrhea, nausea, fatigue, hypotension, edema, and headache.

Tisagenlecleucel became the first CAR T-cell therapy approved by the FDA in August 2017, when the agency authorized the treatment’s use for patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia that is refractory or in second or later relapse.

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

In melanoma, the FDA approved the combination of dabrafenib and trametinib for the adjuvant treatment of patients with BRAF V600E– or V600K–positive stage III melanoma following complete resection.

The approval is based on data from the phase III COMBI-AD study, in which adjuvant treatment with dabrafenib and trametinib reduced the risk of relapse or death by 53% versus placebo for patients with BRAF-mutant stage III disease.

Additionally, 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.

The median RFS was not reached with the combination versus 16.6 months for placebo and RFS was improved with dabrafenib/trametinib across all subgroups. Overall hazard ratios ranged from 0.33 to 0.55 in favor of the combination versus placebo.

Early data for overall survival showed that 86% of patients in the combination arm were alive at 3 years versus 77% with placebo. At an interim analysis, the OS advantage was not yet deemed statistically significant.

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

The FDA has granted a priority review to a biologics license application for cemiplimab as a treatment for patients with metastatic cutaneous squamous cell carcinoma or those with locally advanced CSCC who are ineligible for surgery.

The submitted application was based on results from the phase II EMPOWER-CSCC 1 study, in which the overall response rate was 46.3% in patients with advanced CSCC. Regeneron and Sanofi, the codevelopers of cemiplimab, also submitted supporting data from 2 phase I expansion cohorts of patients with advanced disease. Updated data from these phase I and II studies will be presented at the 2018 ASCO Annual Meeting.

Phase I data for cemiplimab in advanced CSCC, which were reported at the 2017 ASCO Annual Meeting, demonstrated a disease control rate of 69.2%.

Cemiplimab previously received an FDA breakthrough therapy designation in CSCC. The FDA is scheduled to make its decision on the application by October 28, 2018.

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

In non-small cell lung cancer, the FDA has granted a priority review to a supplemental biologics license application for frontline pembrolizumab combined with chemotherapy for patients with metastatic nonsquamous disease.

The application is based on the phase III KEYNOTE-189 trial, in which the addition of pembrolizumab to pemetrexed and either cisplatin or carboplatin in the first-line setting reduced the risk of death by more than 50% in patients with NSCLC without EGFR or ALK mutations.

KEYNOTE-189 is the confirmatory trial to convert the accelerated approval of this regimen into a full approval.

In the study, at a median follow-up of 10.5 months, the estimated 12-month overall survival rate was 69.2% in the pembrolizumab arm versus 49.4% in the control group. The median OS was not reached in the pembrolizumab cohort, compared with 11.3 months in the chemotherapy-alone arm. The OS benefit was observed, irrespective of PD-L1 status.

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

A new drug application for gilteritinib has been submitted to the FDA for the treatment of adult patients with FLT3 mutation–positive relapsed or refractory acute myeloid leukemia.

The NDA is based on data from the ongoing phase III ADMIRAL study, which is evaluating gilteritinib versus salvage chemotherapy in adult patients with FLT3-positive relapse/refractory AML. Astellas Pharma, the developer of gilteritinib, has also submitted an application to Japanese regulatory authorities for marketing approval for the FLT3 inhibitor in the same setting.

Data from the open-label, multicenter ADMIRAL trial have not yet been made available. The coprimary endpoints are overall survival and complete remission or CR with partial hematological recovery.

In October 2017, the FDA granted fast track designation to gilteritinib for adult patients with FLT3 mutation-positive relapsed/refractory AML.

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

In Europe, a 4-week dosing schedule for nivolumab has been approved by the European Commission for the treatment of patients with advanced melanoma and previously treated renal cell carcinoma.

The commission specifically approved a 4-week dosing regimen with 480 mg of nivolumab for these indications. Additionally, the EU approved replacing weight-based dosing with 240 mg every 2 weeks for the 6 nivolumab monotherapy indications approved in the European Union, which are melanoma, non–small cell lung cancer, RCC, classical Hodgkin lymphoma, head and neck squamous cell carcinoma, and urothelial carcinoma.

In March 2018, the FDA approved a supplemental biologics license application adding the 4-week dosing schedule for nivolumab across several of the PD-1 inhibitor’s indications. Physicians now have the option of using either the new 4-week dosing schedule or the previously approved schedule of 240 mg every 2 weeks, now available in a new 240 mg vial.

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

This week, we sat down with Dr Anas Younes of Memorial Sloan Kettering Cancer Center, to discuss initial steps for treatment of patients with diffuse large B-cell lymphoma.

That’s all for today.

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