Multiple Priority Review Designations Highlight Week in Cancer News
Top news of the week in oncology and cancer drug development.
FDA Approves Telotristat Ethyl for Carcinoid Syndrome Diarrhea
The FDA has approved telotristat ethyl (Xermelo) for use in combination with somatostatin analog (SSA) as a treatment for carcinoid syndrome diarrhea in patients with metastatic neuroendocrine tumors (NETs) that cannot be adequately controlled by SSA therapy alone. The safety and efficacy of telotristat ethyl were established in a 12-week, double-blind, placebo-controlled trial in 90 adult participants with well-differentiated metastatic NETs and carcinoid syndrome diarrhea.
Despite the use of SSA at a stable dose for ≥3 months, the patients continued to have 4 to 12 daily bowel movements. Patients continued SSA therapy and were randomized to telotristat ethyl or placebo 3 times daily. In the telotristat ethyl arm, 33% of patients had an average reduction of 2 bowel movements per day compared with 4% of patients on the placebo arm.
FDA Approves Maintenance Lenalidomide for Myeloma
The FDA has approved lenalidomide (Revlimid) as a maintenance therapy for patients with multiple myeloma following autologous hematopoietic stem cell transplant (auto-HSCT). The data for the approval came from 2 large trials (1000+ patients each) that compared maintenance lenalidomide versus no maintenance after auto-HSCT. The primary endpoint of both studies was progression-free survival (PFS).
In CALGB 100104, the median PFS was 5.7 years (95% CI, 4.4-not estimable) with lenalidomide maintenance versus 1.9 years (95% CI,1.6-2.5) for no maintenance, representing a 3.8-year benefit (HR, 0.38; 95% CI, 0.28-0.50). In the IFM 2005-02 trial, the median PFS was 3.9 years (95% CI, 3.3-4.7) versus 2 years (95% CI, 1.8-2.3), respectively, representing a 1.9-year benefit (HR, 0.53; 95% CI, 0.44-0.64). The median overall survival (OS) in CALGB 100104 was 9.3 years (95% CI, 8.5-not estimable) with lenalidomide maintenance versus 7 years (95% CI, 5.9-8.6) for no maintenance (HR 0.59; 95% CI, 0.44-0.78). In the IFM 2005-02 trial, the median OS was 8.8 years (95% CI, 7.4-not estimable) versus 7.3 years (95% CI, 6.7-9.0), respectively (HR, 0.90; 95% CI, 0.72-1.13).
FDA Grants Priority Review to Enasidenib for IDH2-Mutant AML
The FDA has granted a priority review to a new drug application (NDA) for enasidenib (AG-221) as a treatment for patients with relapsed or refractory IDH2-mutated acute myeloid leukemia (AML), according to a statement from Celgene and Agios, the codevelopers of the targeted therapy. The priority review is based on data from the phase I/II AG221-C-001 study, which was presented at the 2015 ASH Annual Meeting. In the single-arm trial, the objective response rate (ORR) with enasidenib was 41% in patients with relapsed or refractory IDH2-mutant AML.
The complete response (CR) rate was 18% and 1.6% had a CR with incomplete platelet recovery (CRp) or incomplete blood count recovery (CRi). Additionally, 6% of patients had a marrow CR (mCR). Under the priority review program, the FDA will decide on the NDA for enasidenib within 6 months compared with the standard 10-month review. The accelerated review timeline follows a fast track designation for enasidenib, which was granted in 2014 and allowed for a rolling submission of data to the FDA. Under the Prescription Drug User Fee Act (PDUFA), the FDA is scheduled to decide on the NDA by August 30, 2017.
FDA Grants Avelumab Priority Review for Metastatic Urothelial Carcinoma
The FDA granted a priority review to a biologics license application for the PD-L1 inhibitor avelumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma whose disease has progressed after platinum-based therapy. Under the Prescription Drug User Fee Act, the FDA will make a final approval decision on the application on or before August 27, 2017. The priority review is based on data from the JAVELIN international development program of avelumab.
In the JAVELIN solid tumor phase Ib trial, avelumab had a response rate of 16% in a cohort of patients with metastatic urothelial carcinoma, including 1 complete response and 6 partial responses. The median duration of treatment was 13 weeks, and the median number of doses administered was 6.5. Median follow-up was 3.5 months. Sixteen patients remained on treatment. The ongoing phase III JAVELIN Bladder 100 trial is evaluating avelumab in the first-line setting as a maintenance treatment in patients with locally advanced or metastatic urothelial carcinoma. The FDA is also currently reviewing an application for avelumab for use as a treatment for patients with metastatic Merkel cell carcinoma.
FDA Grants Ceritinib Priority Review in Frontline ALK+ NSCLC
The FDA granted a priority review to the second-generation ALK inhibitor ceritinib as a first-line treatment for patients with ALK-positive, metastatic non—small cell lung cancer. The priority review is based on findings from the phase III ASCEND-4 trial, in which ceritinib reduced the risk of disease progression or death by 45% compared with standard chemotherapy. The median progression-free survival benefit favoring ceritinib was 8.5 months.
The FDA also granted frontline ceritinib a breakthrough therapy designation for use in patients with ALK-positive NSCLC and brain metastases. Under the priority review, the application for frontline ceritinib will be reviewed within 6 months of submission, instead of the standard 10-month timeframe. Ceritinib was previously approved by the FDA in April 2014 for patients with ALK-positive NSCLC following treatment with the ALK inhibitor crizotinib.
Carfilzomib Improves Survival in Relapsed Multiple Myeloma
Carfilzomib (Kyprolis) plus dexamethasone improved overall survival (OS) by 21% versus dexamethasone plus bortezomib (Velcade) in patients with relapsed or refractory multiple myeloma, according to findings from the phase III ENDEAVOR trial announced by Amgen. The median OS was 47.6 months in the carfilzomib arm versus 40.0 months in bortezomib arm (HR, 0.79; 95% CI, 0.65-0.96). The safety data were consistent with previously reported study outcomes.
The full updated results from the trial will be presented at the 16th International Myeloma Workshop, which is being held in New Delhi from March 1 to 4, 2017. Based on the progression-free survival data from the primary analysis, the FDA approved carfilzomib in January 2016 for use in combination with dexamethasone or with lenalidomide plus dexamethasone for patients with relapsed/refractory multiple myeloma following prior treatment with 1 to 3 lines of therapy.
The 2017 ASCO-SITC Clinical Immuno-Oncology Symposium took place last week in Orlando, Florida. One of the noteworthy abstracts presented showed that treatment with pembrolizumab could elicit long-term survival rates of 21% to 25% for previously-treated patients with PD-L1—positive non–small cell lung cancer compared with 3% to 4% for docetaxel, according to a statistical analysis of findings from the KEYNOTE-010 and -001 trials.
Findings from the analysis shed light on the number of patients with advanced NSCLC expected to benefit for up to 70 months from pembrolizumab. According to survival statistics from the SEER database for 2006 to 2012, the 5-year survival rate was 4.3% for those with lung or bronchus cancer with distant metastases.
2017 BMT Tandem Meetings
The 2017 BMT Tandem Meetings took place from February 22 to 26 at the Gaylord Palms Convention Center in Orlando, Florida. In one of the key studies presented at the meeting the anti-CD19 CAR T-cell therapy axicabtagene ciloleucel, or KTE-C19, had an objective response rate of 76% and a complete response rate of 47% in patients with aggressive non-Hodgkin lymphoma followed for at least 1 month, according to a prespecified interim analysis of the phase II portion of the ZUMA-1 trial. The durable complete response rate at 3 months was 39%, which was 6-fold higher than that in historical controls.
Dendritic Immunotherapy Falters in Phase III RCC Trial
An Independent Data Monitoring Committee (IDMC) has recommended halting the phase III ADAPT trial exploring rocapuldencel-T (AGS-003) for the frontline treatment of metastatic renal cell carcinoma (mRCC), following a futility analysis. Despite this advice, Argos Therapeutics, the company developing the autologous dendritic cell immunotherapy, plans to keep the trial open to conduct further data reviews, according to a statement from the company. In the ADAPT trial, which enrolled 462 patients with mRCC, patients were randomized to receive rocapuldencel-T plus standard therapy compared with standard therapy alone, which primarily consisted of sunitinib (Sutent).
The primary endpoint of the study was overall survival, with secondary endpoints focused on progression-free survival and adverse events. At the analysis, the IDMC concluded that the trial was unlikely to show an improvement in overall survival. Keeping with observations from an earlier phase II study, treatment with rocapuldencel-T was well-tolerated. Following the review, Argos is also examining the data, along with their clinical and scientific advisors. They plan to discuss the findings with the FDA, prior to determining the next steps for the ADAPT trial.