Extended Review for Nivolumab Tops Cancer News Roundup

August 23, 2015

Specialty Pharmacy Times Staff

Article

A look back at recent developments in cancer research.

A look back at recent developments in cancer research.

FDA Expands Brentuximab Vedotin's Hodgkin's Label

The FDA has approved the antibody-drug conjugate brentuximab vedotin as a consolidation therapy following autologous stem cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression, based on the phase III AETHERA trial.

In the study, treatment with the anti-CD30 ADC reduced the risk of disease progression by 43% compared with placebo. The median progression-free survival with brentuximab vedotin was 42.9 versus 24.1 months (HR, 0.57; 95% CI, 0.40-0.81; P = .0013).

The 2-year PFS rate for patients treated with brentuximab vedotin following ASCT was 54%. The hazard ratio for PFS was consistently below 1.00 across all subgroups analyzed in the study, including patients with primary refractory disease. For patients with primary-refractory disease, the 2-year PFS rate was 60% with brentuximab vedotin compared with 42% for placebo.

The estimated 2-year OS rates with brentuximab vedotin and placebo were both 88%. This endpoint was potentially confounded by crossover, as 85% of patients in the placebo arm received brentuximab vedotin when the trial was unblended in September 2014. With this approval, brentuximab vedotin has become the first and only FDA-approved consolidation treatment option available to high risk classical Hodgkin lymphoma patients who undergo a transplant to preserve their post-auto-HSCT remissions.

Second Phase II Atezolizumab NSCLC Study Positive

Atezolizumab (MPDL3280A) met the primary endpoint of objective response in PD-L1—positive patients with advanced non–small cell lung cancer in the phase II BIRCH trial, according to Roche, which manufactures the PD-L1 inhibitor.

The results corroborate the phase II POPLAR data presented at ASCO 2015, in which atezolizumab improved survival versus chemotherapy in pretreated patients with PD-L1—positive NSCLC. Results from BIRCH were not released, but in POPLAR, patients with PD-L1 expression of 2 and 3 on immune/tumor cells had a median OS of 13 months with atezolizumab compared with 7.4 months for those treated with docetaxel (n = 55).

Treatment with atezolizumab was associated with a 44% reduction in the risk of death for this group of patients (HR, 0.56; 95% CI, 0.33-0.95; P = .026). Based on early-stage studies, atezolizumab previously received a breakthrough therapy designation from the FDA as a potential treatment for patients with PD-L1—positive NSCLC following progression on prior therapy, including chemotherapy and targeted therapies.

The BIRCH findings will contribute to ongoing discussions on atezolizumab between Roche and the FDA that were established under this designation. The safety profile for atezolizumab in the BIRCH trial was similar to previous adverse event outcomes reported for the PD-L1 inhibitor. Results from BIRCH are being prepared for presentation at an upcoming medical meeting. At this point, six phase III studies have been launched to explore atezolizumab in the first- and second-line setting for patients with NSCLC across histologies.

Nivolumab Melanoma Review Extended

Recently, the FDA extended the review period for frontline nivolumab in patients with advanced melanoma by 3 months, to allow ample time to review additional data submitted by the PD-1 inhibitor's developer Bristol-Myers Squibb. The updated action date for the new indication is November 27, 2015.

Nivolumab initially received a priority review designation for the new indication on April 30, 2015, based on the phase III CheckMate-066 trial that explored nivolumab in untreated patients with BRAF wild-type advanced melanoma. The new data hope to support an approval that is irrespective of BRAF status, BMS indicated.

Although not specificially indicated, it is likely that the additional data is from CheckMate-067, which looked at nivolumab with or without ipilimumab versus ipilimumab alone in the frontline setting for patients with advanced melanoma. In this study outcomes were similar regardless of BRAF mutation status. For those with BRAF-mutations treated with single-agent nivolumab (n = 98) the median PFS was 5.6 months compared with 4.0 months with single-agent ipilimumab (n = 100; HR, 0.77; 95% CI, 0.54-1.09).

In those with wild-type BRAF melanoma treated with nivolumab (n = 218), the median PFS was 7.9 versus 2.8 months with ipilimumab (HR, 0.50; 95% CI, 0.39-0.63). In late June 2015, the European Commission approved nivolumab as a treatment for patients with advanced melanoma in the first- and later-line settings regardless of BRAF mutation status.

Venetoclax Successful in Pivotal Phase II CLL Trial

Treatment with single-agent venetoclax (ABT-199) has met the primary endpoint of a pivotal phase II study for patients with relapsed or refractory chronic lymphocytic leukemia harboring the 17p deletion, according to top-line findings released by AbbVie and Genentech, the codevelopers of the BCL-2 inhibitor.

The primary endpoint of the open-label, single-arm phase II study was overall response rates assessed using NCI-CWG criteria. Full data from the study were not yet made available and are being submitted for presentation at an upcoming medical meeting. Based on the findings, AbbVie and Genentech are preparing regulatory submissions to the FDA and European Medicines Agency, which they anticipated would be complete by the end of 2015. A preceding phase I study enrolled 105 patients at a median age of 66 years with CLL and small lymphocytic leukemia.

For patients who received the 400 mg or higher dose of venetoclax, the median PFS had not yet been reached at the April 2014 data cutoff. The estimated 24-month PFS rate at this dose level was 59%. The approximate median PFS across all doses was 18 months. For high-risk patients treated at the 400 mg dose or higher, the 24-month PFS rate was 54% (range, 31-71). Venetoclax received a breakthrough therapy designation from the FDA as a potential treatment for patients with 17p deletion CLL in May 2015.

A rolling submission of clinical trial data is permitted under this program, which is intended to expedite the development of new agents. Currently, there are two phase III trials assessing venetoclax in combination with anti-CD20 antibodies for patients with CLL.