The latest news in oncology treatment research.
The latest news in oncology treatment research.
FDA Grants Priority Review to MCNA for Bladder Cancer
The FDA has assigned a priority review designation to the intravesical immunotherapy MCNA as a treatment for patients with high-risk non-muscle invasive bladder cancer following first-line bacillus Calmette-Guérin therapy. A treatment has not been approved in this space since 1998. The priority review was based on findings from an open-label phase III trial, which demonstrated significant activity with MCNA, an immunotherapy that is comprised of mycobacterial cell wall fragments complexed with nucleic acids. Under this review program, the FDA will make a decision on the application for the treatment by February 27, 2016.
Prior to this date, the agency announced plans to hold an advisory meeting to discuss the application. In the pivotal open-label phase III study, 25% of patients treated with MCNA remained disease-free at 1-year, which met the criteria established for the primary endpoint of the study. At 2-years, the disease-free survival rate was 19%. In patients with papillary only tumors, the DFS rate was 35.1% and 32.2% at 1 and 2 years, respectively. Findings from the study were initially presented at the AUA meeting in 2011.
At the time of this presentation, the treatment was being developed by Endo Pharmaceuticals and Bioniche Life Sciences, which later became Telesta Therapeutics. Since the company is small and the treatment is needed, the FDA waived its traditional fees user fees associated with a new drug application, which totaled $2.3 million. See more at: http://www.onclive.com/web-exclusives/fda-grants-intravesical-immunotherapy-priority-review-for-bladder-cancer
Afatinib Application Accepted for Squamous NSCLC
The FDA has accepted an application for afatinib as a treatment for patients with squamous cell non—small cell lung cancer following progression on chemotherapy, according to Boehringer Ingelheim, the manufacturer of the irreversible EGFR inhibitor. Afatinib was also granted orphan drug status. Boehringer reported that a separate regulatory filing for afatinib in the same setting was accepted by the European Medicines Agency.
The two applications were based on results from the phase III LUX-Lung 8 study, which compared second-line afatinib with erlotinib in patients with advanced squamous cell carcinoma of the lung. In the study, afatinib reduced the risk of both disease progression and death by 19%, compared with erlotinib. 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; P = .0077). PFS was 2.6 months with afatinib compared to 1.9 months with erlotinib (HR, 0.81; P = .0103).
The objective response rates were similar between the 2 arms, at 6% and 11%, respectively (P = .0551). A standard review from the FDA takes approximately 10 months, placing a decision in mid-2016.
Medivation Purchases Talazoparib from BioMarin
Medivation has announced that it will purchase the PARP inhibitor talazoparib (BMN-673) from BioMarin Pharmaceutical for $410 million, with additional milestone and royalty payments of up to $160 million. Once the agreement closes, Medivation will become responsible for all global research, development, regulatory, and commercialization costs. Talazoparib is being explored across a variety of solid tumors, and is furthest along in development as a treatment for patients with breast cancer.
In this setting, a number of clinical trials are currently recruiting participants. The open-label phase III EMBRACA study is assessing talazoparib in patients with locally advanced and/or metastatic breast cancer germline BRCA mutations. At this point, Medivation's only FDA-approved agent is enzalutamide, a potent androgen receptor inhibitor for men with prostate cancer. Early research has suggested that PARP1 could be a regulator of AR function, with a potential role for combination strategies in men who become resistant to AR inhibition.
In an investigator-sponsored trial, enzalutamide is being explored with the PARP inhibitor niraparib for patients with metastatic castration-resistant prostate cancer (NCT02500901). Although not yet initiated or announced, a similar study combining enzalutamide with talazoparib seems likely. In a statement, the CEO of medivation, David Hung, MD, said "talazoparib is a great strategic fit for Medivation's oncology portfolio, building on existing strengths as well as potentially allowing Medivation to expand into new oncology indications."
Daratumumab Data Published in NEJM
Findings from a second phase II clinical trial demonstrating the impressive clinical activity of the anti-CD38 monoclonal antibody daratumumab as a monotherapy for patients with heavily pretreated multiple myeloma were published in The New England Journal of Medicine last week. In patients who received daratumumab at 16 mg/kg (n = 42) in the phase I/II GEN501 study, the objective response rate was 36%, which included 2 complete responses and 2 very good partial responses.
At this same dose, the estimated median progression-free survival was 5.6 months and the overall survival rate at 12 months was 77%. These findings add to results on single-agent daratumumab that were presented from the phase II MMY2002 (SIRIUS) study at the 2015 ASCO Annual Meeting. Based on the ASCO results, Janssen Biotech initiated a rolling submission of data to the FDA, as part of a breakthrough therapy designation received in May 2013. This application was completed on July 9, 2015, and included data from SIRIUS and four other studies, including GEN501. Under the Prescription Drug User Fee Act, the FDA is scheduled to assign a review timeline for daratumumab by September 9, 2015.
ASCO Updates NSCLC Guidelines
ASCO has updated its clinical practice guideline for the treatment of patients with stage IV non-small cell lung cancer, based on a systemic review of 73 randomized controlled trials that were published from January 2007 to February 2014. ASCO's previous guideline on the treatment of patients with stage IV NSCLC was published in 2009, with an update on switch maintenance therapy added in 2011. The latest rendition of the guideline focuses on patient histology and molecular subtype for treatment selection.
The revised guideline contained information on a number of therapies, including afatinib, ceritinib, crizotinib, erlotinib, gefitinib, and maintenance therapy. However, given a lack of significant phase III clinical trial data at the time of the analysis, the guideline was unable to make a recommendation regarding the use of PD-1 inhibitors, like nivolumab or pembrolizumab. Additionally, the guideline committee could not make a recommendation concerning the utilization of third-generation EGFR inhibitors, like rociletinib or mereletinib (AZD9291).
The guideline dropped prior recommendations for cetuximab, clarified the role of ALK/EGFR inhibitors, and indicated that an optimal role for ramucirumab remained unclear. Given numerous pending FDA decisions and anticipated results from phase III studies, the guidelines are likely to be updated again in the near future.