Promising Multiple Myeloma Drug Highlights Week in Cancer News

Tesaro Initiates Rolling Submission for Niraparib in Ovarian Cancer

The FDA has granted a fast track designation to niraparib as a treatment for women with recurrent platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer, according to the company developing the PARP inhibitor, Tesaro. Under this designation, the company plans to begin a rolling submission of data from the phase III NOVA for a new drug application.

Full submission of the NDA to the FDA is anticipated before the end of 2016. In the phase III trial, niraparib improved median progression-free survival by 15.5 months versus placebo for patients responding to platinum-based chemotherapy who harbored a germline mutation, according to results released by the company. In those with non—gBRCA-mutated tumors with homologous recombination deficiency-positivity, there was a 9.1-month PFS advantage seen with niraparib versus placebo.

The median PFS in gBRCA mutation carriers was 21.0 months with niraparib versus 5.5 months with placebo, representing a 73% improvement in the risk of progression or death (HR, 0.27; P <.0001). For those with HRD-positive tumors, the median PFS was 12.9 months with niraparib versus 3.8 months with placebo (HR, 0.38; P <.0001).

See more http://www.onclive.com/web-exclusives/tesaro-initiates-rolling-submission-for-niraparib-in-ovarian-cancer

FDA Grants Pembrolizumab Priority Review in Frontline NSCLC

The FDA has granted a priority review to a supplemental biologics license application for pembrolizumab as a first-line treatment for patients with PD-L1—positive non–small cell lung cancer. The sBLA is based on data from the phase III KEYNOTE-024 trial, in which frontline pembrolizumab improved overall survival and progression-free survival versus chemotherapy in patients with NSCLC and PD-L1 expression levels ≥50%.

The ORR was 24.8% in the 101 treatment-naive patients. The median OS was 16.2 months in these patients, and the median PFS was 6.0 months. The median duration of response was 23.3 months. Efficacy outcomes were also determined by PD-L1 status. Among treatment-naive patients with PD-L1 expression ≥50%, the ORR was 50%, the PFS was 12.5 months, and the median OS was not yet reached. The data from the trial have not yet been presented. Along with the priority review, pembrolizumab also received a breakthrough therapy designation in this setting from the FDA. The FDA is scheduled to make a final decision on the sBLA for the PD-1 inhibitor by December 24, 2016, in accordance with the Prescription Drug User Fee Act.

See more http://www.onclive.com/web-exclusives/fda-grants-pembrolizumab-priority-review-in-frontline-nsclc

Selinexor Shows Promise in Heavily Pretreated Myeloma

Selinexor (KPT-330) demonstrated promising clinical activity in patients with heavily pretreated multiple myeloma, according to Karyopharm Therapeutics, the manufacturer of the selective inhibitor of nuclear export. In the phase IIb STORM trial, the overall response rate with selinexor was 20.5% (n = 16) among 78 patients with relapsed/refractory multiple myeloma. In 48 patients with quad-refractory disease, the ORR was 20.8% (n = 10), and in 30 patients with penta-refractory disease, the ORR was 20% (n = 6).

The STORM trial is now being expanded to include an estimated 120 additional patients with penta-refractory multiple myeloma. The responses to selinexor in the STORM trial included very good partial responses and partial responses. Several patients are still receiving treatment. The safety profile for selinexor was similar to previously reported adverse-event data for the drug. Further data from the study will be reported later this year, and if the subsequent findings (expected in early 2018) are consistent with the initial results, Karyopharm plans to submit the selinexor data to the FDA for consideration of an accelerated approval and to the EMA for a potential conditional approval.

See more http://www.onclive.com/web-exclusives/selinexor-shows-promise-in-heavily-pretreated-myeloma

Imetelstat Future Unclear in MDS

The future of imetelstat as a treatment for patients with myelodysplastic syndromes is uncertain following an update on 2 clinical trials from Geron, which is codeveloping the telomerase inhibitor with Janssen. The first study was the open-label phase II IMbark trial, which is examining imetelstat in patients with relapsed/refractory intermediate-2 or high-risk myelofibrosis after the failure of a JAK inhibitor.

Patients received imetelstat intravenously at either 4.7 mg/kg or 9.4 mg/kg every 3 weeks. At an interim analysis, the 4.7 mg/kg arm showed inadequate spleen and symptom response after 12 weeks, resulting in closure of this arm. Patients in this group will be allowed to increase their dose to 9.4 mg/kg, which only showed a "trend" toward satisfying the primary endpoint of response. Despite this trend, new enrollment is going to be halted, until further data are available.

Safety data for imetelstat at the internal review were consistent with previously reported adverse event data for the drug in hematologic myeloid malignancies. The second study, labeled IMerge, will continue as planned. Efficacy in this study is on par with expectations. This study is exploring imetelstat at 7.5 mg/kg in transfusion dependent relapsed/refractory patients with low or intermediate-1 risk MDS after the failure of an erythropoiesis stimulating agent.

See more http://www.onclive.com/web-exclusives/imetelstat-future-unclear-in-mds

Venetoclax/Rituximab Combo Active in CLL

Combining the BCL-2 inhibitor venetoclax with the anti-CD20 agent rituximab led to objective responses in 86% of patients with relapsed/refractory chronic lymphocytic leukemia, showed results from the phase Ib M13-365 study that was presented at the 2016 SOHO Meeting. The data showed that 51% of patients achieved complete response with or without complete hematologic recovery and 35% attained partial response.

The median time to complete response was 8.5 months. Choi reported that 13 patients who achieved deep objective responses stopped venetoclax after median treatment duration of 10 months. In 10 of 13 cases, patients attained MRD-negative complete responses, and 1 patient had an MRD-negative partial response. Two additional patients with MRD-positive complete responses also stopped venetoclax.

Based on data from this trial, the FDA granted a breakthrough therapy designation to venetoclax in January 2016 for use in combination with rituximab to treat patients with relapsed/refractory CLL. The designation will expedite the development and review of the combination in this setting.

See more http://www.onclive.com/web-exclusives/venetoclaxrituximab-combo-active-in-cll