Lung Cancer Drug Approval Highlights Oncology News Roundup

Top news of the week in cancer drug development.

Nivolumab Approved for Nonsquamous NSCLC

The FDA approved nivolumab for patients with nonsquamous non—small cell lung cancer who progressed on or following platinum-based chemotherapy, based on data from the phase III CheckMate-057 trial. The FDA made the decision approximately 3 months ahead of the PDUFA date for the application.

In the data that led to approval, second-line nivolumab reduced the risk of death by 27% versus docetaxel in patients with nonsquamous NSCLC, including a 60% risk reduction among patients with the highest levels of PD-L1 expression. In a longer follow-up of data from the study presented at ECC, the 2-year OS rate with nivolumab was 39% compared with 23% for docetaxel.

ORR was 19% with the PD-1 inhibitor compared with 12% with chemotherapy (odds ratio = 1.72; P = .0246). The IHC 28-8 pharmDx test diagnostic for PD-L1 testing was approved along with nivolumab, to help guide treatment decisions. The test is a "complementary," not a "companion," diagnostic, meaning its use is not mandated prior to administering nivolumab.

In the 057 trial, higher PD-L1 expression was associated with improved survival outcomes among the 78% of patients for whom PD-L1 status was detectable. The reduction in the risk of death was 57% (median OS = 18.2 months) and 60% (median OS = 19.4 months) for patients expressing PD-L1 on ≥5% and ≥10% of their tumor cells, respectively.

With the recent decision, nivolumab is now approved for both squamous and nonsquamous NSCLC.

See more at: http://www.onclive.com/web-exclusives/fda-expands-nivolumab-lung-cancer-approval

Abemaciclib Granted Breakthrough Designation for Breast Cancer

The FDA has granted the CDK4/6 inhibitor abemaciclib (LY2835219) a breakthrough therapy designation as monotherapy for heavily pretreated patients with refractory HR-positive advanced breast cancer, based on data from a phase I study.

In the small clinical trial, single-agent abemaciclib demonstrated an objective response rate of 33.3% in patients with heavily pretreated (7 median therapies) HR-positive breast cancer (n = 36). When including those with stable disease for ≥24 weeks, the clinical benefit rate with abemaciclib was 61.1%.

The median duration of response was 13.4 months and the median progression-free survival was 8.8 months. Patients with HR-negative disease did not experience a response with abemaciclib monotherapy. The stable disease rate at ≥24 weeks was 11.1%.

The median PFS was 1.1 months. The response rate in HR and HER2-positive breast cancer was 33.3%.

In the HR-positive, HER2-negative group, the response rate was 66.7%. In a separate arm of the study, the combination of abemaciclib and fulvestrant demonstrated an ORR of 21.1% in patients with HR-positive breast cancer treated with 4 prior therapies.

In those with measurable disease at baseline (57.9%), there was a 36.4% response rate. The rate of stable disease at ≥24 weeks was 42.1%, for a clinical benefit rate of 63.2% across the full population. At the time of the analysis, the duration of response had not yet been reached and the median PFS was 10 months.

See more at: http://www.onclive.com/web-exclusives/fda-grants-abemaciclib-breakthrough-status-for-refractory-breast-cancer

Vemurafenib/Cobimetinib Improves Survival in Melanoma

The combination of vemurafenib and cobimetinib demonstrated a statistically significant improvement in overall survival compared with vemurafenib alone for previously untreated patients with BRAFV600-mutant unresectable or metastatic melanoma, according to new findings from the coBRIM study.

In previous data from the phase III study, the combination of vemurafenib and cobimetinib demonstrated a 5-month improvement in progression-free survival compared with vemurafenib plus placebo. This benefit translated to a 42% reduction in the risk of progression or death.

The median PFS with cobimetinib and vemurafenib was 12.25 months compared with 7.2 months for vemurafenib and placebo (HR, 0.58). The ORR was 69.6% versus 50%, for cobimetinib/vemurafenib and vemurafenib/placebo, respectively.

The absolute difference in ORR between the two arms was 19.64%. OS data and long-term safety findings are being prepared for presentation at an upcoming medical meeting.

The FDA is currently reviewing data from the coBRIM study as part of a new drug application for the combination of cobimetinib and vemurafenib in melanoma. Under the Prescription Drug User Fee Act, the agency is scheduled to make a decision regarding this submission by November 11, 2015.

See more at: http://www.onclive.com/web-exclusives/cobimetinibvemurafenib-combo-improves-survival-in-melanoma

Lilly Shifts Focus Toward Immuno-Oncology

Lilly Oncology is planning to expand its lab space at the Alexandria Center for Life Science in New York City to include a translational immuno-oncology hub that will serve as a “portal” for collaborating with researchers from nearby academic medical centers and biopharmaceutical companies.

The company plans to add 30,000 square feet of lab space and approximately 50 new jobs to its research facilities at the East River Science Park, where about 130 people are currently employed in research and development. The new lab is scheduled for completion in 2016.

Lilly officials say the lab expansion is part of a more aggressive approach to immunotherapy development for the Indianapolis-based company, which lags behind its competitors in bringing checkpoint blockade agents to market. The company’s strategy involves numerous partnerships, including cooperating with industry rivals on combination drug trials.

Lilly’s immunotherapy projects include the small molecule galunisertib (LY2157299), which selectively blocks signaling in the transforming growth factor β pathway. The agent is being evaluated with and without the multikinase inhibitor sorafenib in phase II studies in hepatocellular carcinoma.

Additionally, a phase Ib/II study will test the agent in combination with the PD-1 inhibitor nivolumab in advanced cancers including solid tumors, HCC, non—small cell lung cancer, and glioblastoma.

See more at: http://www.onclive.com/web-exclusives/lilly-expanding-nyc-research-hub-to-focus-on-immunotherapy-combos

Avelumab Granted Fast Track Designation for Merkcel Cell Carcinoma

The PD-L1 inhibitor avelumab recently received an orphan drug designation and a fast track designation for patients with Merkel cell carcinoma, raising hopes that new therapies could be on the horizon for this rare aggressive type of skin cancer. Although results have not yet been announced for avelumab in MCC, the two designations indicate promise for the treatment.

Together, these designations will help facilitate the submission of data for avelumab to the FDA, if positive results are demonstrated. At this time, there are no FDA-approved therapies for patients with this rare disease.

Hinting at the activity for this class in patients with MCC, impressive early findings were presented from a phase II study for pembrolizumab at the 2015 European Cancer Congress. Of 14 evaluable patients, 10 responded to pembrolizumab, representing a 71% response rate.

These responses consisted of 2 complete responses and 8 partial responses. Three patients had progressive disease and 1 patient had stable disease at the time of the analysis on September 18, 2015. Both agents continue to be explored for patients with MCC.

See more at: http://www.onclive.com/web-exclusives/pembrolizumab-avelumab-show-promise-in-merkel-cell-carcinoma