FDA Submissions Highlight Week in Cancer News

FDA Approves Blinatumomab for Pediatric ALL

The FDA has granted an accelerated approval to blinatumomab for the treatment of pediatric and adolescent patients with Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia. The approval of the anti-CD19 immunotherapy in this setting was based on data from a single-arm phase I/II trial, known as Study 205, which met its primary phase II endpoint of complete remission within the first 2 cycles of blinatumomab.

Treatment of all patients (n = 93) in the trial has been completed, and individuals are now being assessed for long-term efficacy. Complete results for all 93 patients have not yet been presented. In previously published data from phase I of Study 205, the CR rate was approximately 32% among 41 patients with relapsed/refractory ALL.

Among the patients who achieved a CR, 77% were minimum residual disease—negative, the median relapse free survival was 8.3 months, and the median overall survival was 5.7 months. Preliminary results for 39 patients from the phase II part of the study showed that the CR rate was 31% (n = 12). Among patients reaching a CR, 42% were MRD-negative, the median RFS was 5.6 months, and the median OS was 4.3 months.

See more: http://www.onclive.com/web-exclusives/fda-approves-blinatumomab-for-pediatric-acute-lymphoblastic-leukemia

FDA Approves Ofatumumab Combination for Relapsed CLL

The FDA has approved ofatumumab in combination with fludarabine and cyclophosphamide as a treatment for patients with relapsed chronic lymphocytic leukemia, based on an improvement in progression-free survival in the phase III COMPLEMENT-2 study. In the open-label study, the median PFS was 28.9 months with the addition of ofatumumab to chemotherapy compared with 18.8 months with fludarabine and cyclophosphamide alone (HR, 0.67; P = .0032).

The overall response rate with the triplet was 84% versus 68% in the control arm (P = .0003), with complete response rates of 27% versus 7%, respectively. Additionally, there was a numerical improvement in median OS with ofatumumab at 56.4 months versus 45.8 months with chemotherapy alone; however, the result was not statistically significant (HR, 0.78; P = .1410).

See more: http://www.onclive.com/web-exclusives/ofatumumab-combination-approved-for-relapsed-cll

Atezolizumab Improves Survival in Phase III Lung Cancer Study

Atezolizumab improved survival compared with docetaxel in patients with advanced non—small cell lung cancer following the failure of platinum-based chemotherapy, according to findings from the phase III OAK trial. The survival benefit was observed regardless of PD-L1 status. The company also noted that the safety profile for atezolizumab in the OAK trial was consistent with previously reported adverse event data for the drug.

Genentech plans to present the complete results from the study at a medical meeting this year. In April 2016, the FDA granted a priority review to atezolizumab for the treatment of patients with locally advanced or metastatic NSCLC who express PD-L1 and have progressed after a platinum-containing regimen. Under the expedited priority program, the FDA will issue a final decision on approval by October 19, 2016.

See more: http://www.onclive.com/web-exclusives/atezolizumab-improves-survival-in-phase-iii-lung-cancer-study

FDA Submission Completed for Brigatinib in ALK-Positive NSCLC

A new drug application has been submitted for brigatinib as a potential treatment for patients with advanced ALK-positive non—small cell lung cancer following resistance or intolerance to crizotinib. The application was based on findings from the phase II ALTA study, which was presented at the 2016 ASCO Annual Meeting, along with results from an earlier phase I/II trial. In ALTA, the confirmed objective response rate for brigatinib at 180 mg daily was 54%, which included a complete response rate of 4%.

In those with measurable, active brain metastases treated with the 180 mg dose (n = 18), the intracranial ORR was 67%. Median progression-free survival was 12.9 months. The application was completed following a rolling submission of data, which was permitted as part of a breakthrough therapy designation that was received in October 2014. Ariad has requested a priority review for the ALK inhibitor, under which the FDA would make a decision 4 months earlier than a standard review. The FDA will assign a regulatory timeline within 60 days.

See more: http://www.onclive.com/web-exclusives/fda-submission-completed-for-brigatinib-in-alkpositive-nsclc

Binimetinib NDA Accepted, ODAC Planned for NRAS-Mutant Melanoma

The FDA has assigned a standard review designation to a new drug application for binimetinib as a treatment for patients with NRAS-mutant advanced melanoma. Additionally, while accepting the application, the agency advised Array BioPharma of plans to call an ODAC meeting as part of the review process, to discuss the drug's risks and benefits.

A date for this meeting has not yet been scheduled. The application for binimetinib was based on data from the phase III NEMO study, which was presented at the 2016 ASCO Annual Meeting. In the open-label study, median progression-free survival with binimetinib was 2.8 versus 1.5 months with dacarbazine, representing a 38% reduction in the risk of progression or death (HR, 0.62; P <.0001). The ORR with binimetinib was 15%, including 1 complete response, compared with 7% for dacarbazine. The median OS with binimetinib was 11.0 months compared with 10.1 months with dacarbazine (HR, 1.00; P = .4). Under the Prescription Drug User Fee Act, the agency is scheduled to make a decision on the NDA by June 30, 2017.

See more: http://www.onclive.com/web-exclusives/fda-accepts-binimetinib-nda-for-nras-mutant-melanoma

EC Approves Crizotinib for ROS1-Positive NSCLC

The European Commission has approved crizotinib as a treatment for patients with advanced ROS1-positive non—small cell lung cancer, based on an improvement in objective response rate in a phase I study. Findings from the single-arm 50-patient study that led to the approval were published in The New England Journal of Medicine in 2014. In this study, crizotinib showed an ORR of 66% with a median duration of response of 18.3 months by independent review.

The median time to first response was 7.9 weeks and the median duration of response was 17.6 months. At the time of the analysis, 64% of patients were still responding to therapy, with a median duration of treatment of 64.5 weeks. The median progression-free survival with crizotinib was 19.2 months. At a median follow-up for overall survival of 16.4 months, the 12-month OS rate was 85%. The median had not been reached.

The approval decision followed a positive recommendation from the Committee for Medicinal Products for Human Use. In Europe, crizotinib is also indicated as both a first- and second-line treatment option for patients with ALK-positive NSCLC.

See more: http://www.onclive.com/web-exclusives/ec-approves-crizotinib-for-ros1positive-nsclc