Upcoming FDA Decisions on Cancer Drugs Highlights Oncology News Roundup

Top news of the week in oncology drug development.

Nivolumab Receives RCC Breakthrough Designation

The FDA granted nivolumab a breakthrough therapy designation for the treatment of patients with advanced renal cell carcinoma, which will expedite the development and review process substantially. The designation is based on the CheckMate-025 trial, which was stopped early in July after an independent panel determined that nivolumab improved overall survival versus everolimus in patients with advanced RCC.

The CheckMate-025 data will be presented at the 2015 European Cancer Congress later this week. BMS plans to submit the data for regulatory approval later this year. OS was the primary endpoint of the study, with secondary outcome measures focused on progression-free survival and objective response rate. The study enrolled 821 patients with mRCC following treatment with a prior therapy. In a prior phase II study in patients with previously treated mRCC a similar 2-mg/kg dose demonstrated a PFS of 4 months, an ORR of 22%, and an OS of 25.5 months. According to BMS, this is the first study in mRCC to demonstrate a survival advantage with an immunotherapy.

See more at: http://www.onclive.com/web-exclusives/fda-grants-nivolumab-breakthrough-designation-in-renal-cell-carcinoma

Maintenance Ofatumumab Receives Priority Review

The FDA granted a priority review designation to ofatumumab as a maintenance therapy for patients with relapsed chronic lymphocytic leukemia following a response to second- or third-line therapy. The application for ofatumumab is based on a near doubling in progression-free survival seen with the treatment compared with observation in the phase III PROLONG trial.

In the open-label study, maintenance ofatumumab demonstrated a median PFS of 28.6 versus 15.2 months with observation, representing a 52% reduction in the risk of progression (HR, 0.48; P <.0001). Additionally, the time to next therapy was 10.6 months longer with ofatumumab compared with observation (HR, 0.63; P = .0076). Data from the PROLONG trial, which were presented at the 2014 ASH Annual Meeting, were also submitted to the European Medicines Agency in early July 2015 by Novartis, which acquired ofatumumab from GlaxoSmithKline as part of a multi-billion-dollar product exchange. Under the priority review designation, the FDA will make a decision on the application by January 21, 2016.

See more at: http://www.onclive.com/web-exclusives/fda-grants-priority-review-to-maintenance-ofatumumab-in-cll

Carfilzomib Receives Priority Review for Earlier Use

The FDA granted a priority review designation to carfilzomib in combination with dexamethasone for patients with relapsed multiple myeloma following prior treatment with at least one therapy, based on findings from the phase III ENDEAVOR trial. In the study, carfilzomib and dexamethasone reduced the risk of progression by 47% compared with bortezomib and dexamethasone. The median progression-free survival with carfilzomib was 18.7 versus 9.4 months with bortezomib (HR, 0.53; P <.0001). The advantage in PFS seen with carfilzomib was consistent across subgroups. The median OS was 24.3 months in the bortezomib arm but had not yet been reached in the carfilzomib arm (HR, 0.79; P = .066).

However, at the time of the primary analysis, survival data were not yet mature. The ORR was 77% with carfilzomib versus 29% with bortezomib. The complete response rate with carfilzomib was 13% versus 6% with bortezomib. The rate of very good partial response or better with carfilzomib was 54% compared with 29% with bortezomib. Under the priority review program, the FDA will make a decision by January 22, 2016.

See more at: http://www.onclive.com/web-exclusives/carfilzomib-granted-priority-review-for-relapsed-multiple-myeloma

Vaccine Effective in Early Cervical Cancer Study

The vaccine ADXS11-001 (axalimogene filolisbac) demonstrated a 12-month overall survival rate of 38.5% in 26 patients with persistent or recurrent metastatic cervical cancer who had progressed on at least one prior line of systemic therapy, according to phase II study data. The median OS with ADX211-011 was 7.7 months, which is expected to increase as the data mature.

Historically, patients with persistent or recurrent metastatic cervical cancer who have failed at least one line of therapy have an estimated survival of 4 to 7 months and limited treatment options. ADXS11-001 is a live-attenuated listeria monocytogenes cancer vaccine. Advaxis has submitted a Special Protocol Assessment request to the FDA for a phase III study evaluating the safety and efficacy of ADXS11-001in high-risk, locally advanced cervical cancer.

The SPA review process remains ongoing. In an interview with the lead investigator, Thomas Herzog, MD, he called the data a good signal of efficacy; however, he emphasized that it is still early phase data. He noted that the phase III study would be designed slightly different, with progression-free survival as the main endpoint and OS as a secondary outcome measure.

See more from the interview at: http://www.onclive.com/web-exclusives/novel-immunotherapy-shows-promise-in-metastatic-cervical-cancer

What's Next?

The next two quarters promise to be busy with the following upcoming FDA decisions looming:

• Nivolumab Plus Ipilimumab in Melanoma - September 30, 2015
• Pembrolizumab all histologies NSCLC - October 2, 2015
• Captisol-enabled melphalan in myeloma - October 23, 2015
• MM-398 for Pancreatic Cancer - October 24, 2015
• T-VEC in metastatic melanoma - October 27, 2015
• Adjuvant Ipilimumab in Melanoma - October 28, 2015
• Trabectedin in Soft Tissue Sarcoma - November 3, 2015
• Cobimetinib/Vemurafenib in BRAF+ melanoma - November 11, 2015
• Dabrafenib/Trametinib Full Approval for BRAF+ melanoma - November 15, 2015
• Nivolumab in frontline Melanoma - November 27, 2015
• TAS-102 for recurrent mCRC - December 19, 2015
• Pembrolizumab for Frontline Melanoma - December 19, 2015
• Pembrolizumab for Ipilimumab-Refractory Melanoma - December 24, 2015
• Nivolumab for Nonsqaumous NSCLC - January 2, 2016
• Maintenance ofatumumab for CLL - January 21, 2016
• Carfilzomib for Relapsed Myeloma - January 22, 2016
• MCNA for Bladder Cancer - February 27, 2016 (ODAC First)
• Osimertinib for T790M+ NSCLC - March 1, 2016
• Elotuzumab for Pretreated Myeloma - March 1, 2016
• Alectinib for ALK+ NSCLC - March 4, 2016
• Daratumumab for Pretreated Myeloma - March 9, 2016
• Ixazomib for Pretreated Myeloma - March 10, 2016
• Rociletinib for T790M+ NSCLC - April 3, 2016 (expected)