New Lung Cancer, Leukemia Drugs Highlight Week in Cancer News

FDA Accepts sNDA for Pembrolizumab in NSCLC

The FDA has accepted a supplemental new drug application for pembrolizumab as a treatment for patients with advanced non—small cell lung cancer with PD-L1 expression on ≥1% of tumors cells, according to the developer of the PD-1 inhibitor, Merck.

The new application is based on an improvement in overall survival with pembrolizumab versus chemotherapy for patients with NSCLC in the open-label phase II/III KEYNOTE-010 trial. In the open-label study, median overall survival was 10.4 months with the FDA-approved dose of 2 mg/kg of pembrolizumab compared with 8.5 months with docetaxel in those with >1% PD-L1 expression (HR, 0.71; P = .0008).

With a larger dose of pembrolizumab (10 mg/kg), the median OS was 12.7 months, representing a 39% reduction in the risk of death versus docetaxel (HR, 0.61; P <.0001). The sNDA is meant to provide supporting evidence to convert the accelerated approval granted to the medication in October 2015 to a full indication. Additionally, the new data could lessen the PD-L1 expression threshold to ≥1% of cells. A standard FDA review is scheduled to last 10 months.

See more at: http://www.onclive.com/web-exclusives/fda-accepts-application-to-expand-pembrolizumab-nsclc-indication

Rindopepimut Misses OS Endpoint in Phase III Study

Treatment with rindopepimut plus temozolomide failed to improve overall survival compared with temozolomide and a control for patients with newly diagnosed EGFRvIII-positive glioblastoma multiforme, according to topline findings from the phase III ACT IV study released by Celldex Therapeutics. In the topline findings from the study, the median OS with rindopepimut was 20.4 months compared with 21.1 months in the control arm (HR, 0.99).

Based on this assessment, which was conducted by an independent data safety and monitoring board, the study was discontinued, according to Celldex; however, the immunotherapy will continue to be offered in the phase III trial and compassionate use programs. According to Celldex, the rindopepimut combination showed OS data similar to expectations in the phase III study while patients in the control arm significantly outperformed.

The level of activity expected for rindopepimut in the phase III study had been established in a prior phase II trial named ReACT. This trial demonstrated a significant improvement in OS, which culminated in a breakthrough therapy designation from the FDA for rindopepimut in February 2015.

See more at: http://www.onclive.com/web-exclusives/rindopepimut-misses-os-endpoint-in-phase-iii-glioblastoma-trial

Frontline Ibrutinib Approved for CLL

The FDA has approved ibrutinib for the frontline treatment of chronic lymphocytic leukemia, based on data from the RESONATE-2 trial. In the phase III study, ibrutinib reduced the risk of progression or death by 84% versus chlorambucil in previously untreated patients with CLL or small lymphocytic lymphoma (HR, 0.16; 95% CI, 0.09-0.28). At a median follow-up of 18.4 months, the median progression-free survival was not yet reached with ibrutinib versus 19 months with chlorambucil (P <.0001).

The median 18-month PFS rates were 94% and 45%, respectively, and the results were consistent across subgroups. The hazard ratio for OS was 0.16 with ibrutinib versus chlorambucil (P = .0010). The 24-month OS rates were 98% versus 85%, respectively. As per independent review, objective response rate was 86% with ibrutinib, with 4.4% of those being complete responses, versus 35.3% with chlorambucil, 1.5% of them complete responses. The FDA previously approved ibrutinib for pretreated CLL, pretreated mantle cell lymphoma, and Waldenström's macroglobulinemia.

See more at: http://www.onclive.com/web-exclusives/fda-approves-ibrutinib-for-frontline-cll

Blinatumomab Submitted for Pediatric ALL

A supplemental biologics license application has been submitted to the FDA to expand the approval of blinatumomab to include the treatment of pediatric and adolescent patients with Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia. The sBLA is based on data from a single-arm phase I/II trial, known as study 205, in which blinatumomab induced complete remissions in a clinically meaningful number of pediatric patients with relapsed/refractory ALL, according to Amgen, the manufacturer of the anti-CD19 immunotherapy.

Study 205 is a multicenter, dose-finding, efficacy trial that accrued patients aged <18 years with Ph- B-cell precursor ALL that was refractory, had relapsed at least twice, or relapsed after an allogeneic HSCT. All patients in the trial have completed therapy and are being observed for long-term outcomes. The data will be submitted for publication, Amgen reported. The FDA granted blinatumomab an accelerated approval in this setting in December 2014, based on phase II data demonstrating strong clinical activity with the agent in adult patients with ALL.

See more at: http://www.onclive.com/web-exclusives/fda-approval-sought-for-blinatumomab-in-pediatric-acute-lymphoblastic-leukemia

CHMP Recommends Afatinib for Second-Line NSCLC

Afatinib has received a positive recommendation from the Committee for Medicinal Products for Human Use as a treatment for patients with advanced squamous cell non—small cell lung cancer following progression on platinum-based chemotherapy, according to Boehringer Ingelheim. The CHMP opinion, which recommends that the treatment should gain approval from the European Medicines Agency in this setting, is based on data from the phase III LUX-Lung 8 trial.

In the study, second-line afatinib reduced the risk of both disease progression and death by 19%, compared with erlotinib in patients with advanced squamous cell carcinoma of the lung. At a median follow-up of 18.4 months, OS was 7.9 months versus 6.8 months with afatinib versus erlotinib, respectively (HR, 0.81; 95% CI, 0.69-0.95; P = .0077). PFS was 2.6 months with afatinib compared to 1.9 months with erlotinib (HR, 0.81; 95% CI, 0.69-0.96; P = .0103). The objective response rates were similar between the 2 arms, at 6% and 11%, respectively (P = .0551).

See more at: http://www.onclive.com/web-exclusives/chmp-recommends-afatinib-for-second-line-nsclc