FDA Tabs Director for New Oncology Center in Top Cancer News

Recent advances and updates in oncology and cancer drug development.

Binimetinib NDA Submitted for NRAS+ Melanoma

A new drug application was submitted for binimetinib as a potential treatment for patients with advanced NRAS-mutant metastatic melanoma. The submission of the NDA was based on findings from the phase III NEMO trial, which was presented at the 2016 ASCO Annual Meeting.

In the open-label study, median progression-free survival with binimetinib was 2.8 versus 1.5 months with dacarbazine, representing a 38% reduction in the risk of progression or death (HR, 0.62; P <.0001). The median OS with binimetinib was 11.0 months compared with 10.1 months with dacarbazine (HR, 1.00; P = .4); however, these data were still being fully analyzed. The ORR with binimetinib was 15%, including 1 complete response, compared with 7% for dacarbazine. The FDA will assign a review timeline for the application within 60 days.

See more: http://www.onclive.com/web-exclusives/fda-approval-sought-for-binimetinib-in-nrasmutant-melanoma

Ibrutinib Granted Breakthrough Status for GVHD

The FDA has granted a breakthrough therapy designation to ibrutinib has a potential treatment for patients with chronic graft-versus-host-disease after failure of one or more lines of systemic therapy. The designation was based on findings from a phase Ib/II study, in which single-agent ibrutinib demonstrated an objective response rate of 55% for patients with steroid-dependent or refractory cGVHD.

Moreover, responses to ibrutinib appeared durable, with a biomarker analysis indicating activity in B and T cells. Of 22 patients, 12 had responded to treatment with ibrutinib. Responses consisted of 1 complete response and 11 partial responses. Responses continued for 49 weeks for 3 patients in the study, and an additional 3 patients were treated and responded for 23 weeks, showing early signs of durability. A majority of responders (92%) were able to reduced (n = 10) or discontinue (n = 1) corticosteroids.

See more: http://www.onclive.com/web-exclusives/ibrutinib-granted-breakthrough-designation-for-chronic-gvhd

Niraparib Improves PFS in Ovarian Cancer

Maintenance therapy with niraparib improved progression-free survival compared with placebo for patients with recurrent ovarian cancer harboring a germline BRCA mutation or homologous recombination deficiency, according to top-line findings from the phase III NOVA trial. In the study, niraparib improved median PFS by 15.5 months versus placebo for patients responding to platinum-based chemotherapy who harbored a gBRCA mutation.

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). In those with non-gBRCA-mutated tumors with HRD-positivity, there was a 9.1-month PFS advantage seen with niraparib versus placebo. 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). Based on these results, Tesaro plans to submit regulatory filings to the FDA and EMA.

See more: http://www.onclive.com/web-exclusives/maintenance-niraparib-improves-pfs-in-ovarian-cancer

Regorafenib New Second-Line Standard of Care for HCC

Second-line treatment with regorafenib improved overall survival by 2.8 months compared with placebo for patients with unresectable hepatocellular carcinoma who progressed on sorafenib, according to findings from the phase III RESORCE trial. In the study, the median OS was 10.6 months with regorafenib compared with 7.8 months for placebo plus best supportive care, representing a 38% reduction in the risk of death with the multikinase inhibitor (HR, 0.62; P<.001).

Median PFS was 3.1 months in the regorafenib arm compared with 1.5 months in the placebo group, representing a 54% reduction in the risk of progression or death (HR, 0.46; P <.001). The ORR with regorafenib was 10.6% versus 4.1% with placebo (P = .005). When considering stable disease, the overall disease control rate was 65.2% with the multikinase inhibitor versus 36.1% with placebo. Findings from the phase III study will be submitted to the FDA and European Medicines Agency for potential approval, according to Bayer Pharmaceuticals.

See more: http://www.onclive.com/conference-coverage/2016-world-GI/secondline-regorafenib-boosts-survival-in-hcc

ODAC Subcommittee Endorses 5 Agents for Pediatric Use

Members of the pediatric subcommittee of ODAC voiced their support for new clinical trials examining promising cancer agents in pediatric patients with cancer. During the 2-day meeting, the panel heard representatives from 5 pharmaceutical companies discuss ongoing or planned early stage pediatric trials exploring atezolizumab, LOXO-101, entrectinib, venetoclax, and tazemetostat. The panelists reacted favorably to the companies’ presentations, supporting each of the 5 pediatric development plans.

There are studies exploring these studies currently ongoing across a number of pediatric indications, with the exception of venetoclax. Atezolizumab is being explored primarily in those expressing PD-L1 while LOXO-101 and entrectinib are being looked at in molecularly defined subgroups, specifically for TRK. Tazemetostat will be explored in INI1-negative tumors and venetoclax is being looked at in high-risk populations.

See more: http://www.onclive.com/web-exclusives/fda-panel-endorses-early-trials-of-promising-anticancer-agents-in-pediatric-patients

Carfilzomib's European Indication Expanded for Myeloma

The European Commission has approved carfilzomib in combination with dexamethasone for adult patients with multiple myeloma who have received at least one prior therapy, based on findings from the phase III ENDEAVOR trial. In the study, the median progression-free survival with carfilzomib plus dexamethasone was 18.7 versus 9.4 months with bortezomib plus dexamethasone, representing a 47% reduction in the risk of progression or death (HR, 0.53; P <.0001).

The objective response rate was 77% with carfilzomib versus 29% with bortezomib. 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 complete response rate with carfilzomib was 12.5% versus 6.2% with bortezomib. The rate of very good partial response or better with carfilzomib was 54% compared with 29% with bortezomib.

See more: http://www.onclive.com/web-exclusives/ec-grants-expanded-approval-for-carfilzomib-in-myeloma

Nelipepimut-S Falls Short in Phase III Breast Cancer Trial

A phase III trial investigating the immunotherapy vaccine nelipepimut-S for the prevention of recurrence in early-stage breast cancer has been stopped due to futility. The halting of the trial, which was known as PRESENT, followed a recommendation from the Independent Data Monitoring Committee based on a planned safety and futility interim analysis that was triggered after 70 qualifying disease-free survival events were reached.

Nelipepimut-S had previously demonstrated a statistically significant increase in DFS in node-positive, HER2 1+ and 2+ patients with early-stage breast cancer in preliminary phase I and II trials. The vaccine in combination with sargramostim and GM-CSF appeared to be well tolerated and effective at raising HER2 immunity. Data from the study will be fully analyzed and a conference call is scheduled that will explore the findings and the future of the oncology/hematology development program at Galena Biopharma.

See more: http://www.onclive.com/web-exclusives/phase-iii-nelipepimuts-study-in-breast-cancer-halted-after-futility-review

OCM Launches With Nearly 200 Practices

A year after announcing its intention to launch the Oncology Care Model alternative payment plan for oncology care, The Centers for Medicare & Medicaid Services said it has 196 practices enrolled across the United States and that the official start date is Friday, July 1. The OCM is designed to reduce the outlay for oncology spending while improving the quality of care. CMS said this will be achieved with financial incentives that encourage better coordination of care and elimination of unnecessary care.

See more: http://www.onclive.com/web-exclusives/cms-announces-practices-participating-in-ocm-and-launch-date

Pazdur Named Head of Oncology

Richard Pazdur, MD, has been named the acting director of the FDA’s newly created Oncology Center of Excellence, which is aimed to expedite the development of novel combination products and support an integrated approach to oncology research.

The OCE is a component created from Vice President Joseph Biden’s National Cancer Moonshot Initiative, which aims to double the current rate of cancer research and make a decade of advances in prevention, diagnosis, and care in 5 years. The OCE will be comprised of a cross-center regulatory approach to enhance the coordination of clinical review across oncology-related drugs, biologics, and medical devices.

See more: http://www.onclive.com/web-exclusives/richard-pazdur-md-named-head-of-new-oncology-center-of-excellence