Breakthrough Designations Highlight Week in Cancer News

Nivolumab Receives Breakthrough Designation for Bladder Cancer

The FDA has granted nivolumab a breakthrough therapy designation for the treatment of patients with unresectable locally advanced or metastatic urothelial carcinoma after the failure of a platinum-containing regimen. The designation was primarily based on findings from the phase II CA209-275 study, which has not yet been presented, with additional supportive data also considered by the FDA. Data for nivolumab in this setting from another study were reported at the 2016 ASCO Annual Meeting.

In this study, single-agent nivolumab had an overall response rate of nearly 24.4% in patients with advanced or metastatic urothelial carcinoma. The median progression-free survival was 2.78 months (95% CI, 1.45-5.85) and the median overall survival was 9.72 months (95% CI, 7.26-16.16). The 1-year OS rate was 45.6%. Among patients with PD-L1 levels ≥1%, ORR was 24%. Patients with PD-L1 expression <1%, had an ORR of 26.2%.

See more at: http://www.onclive.com/web-exclusives/fda-grants-nivolumab-breakthrough-designation-for-advanced-bladder-cancer

Lutathera Receives Priority Review for NETs

The FDA has granted a priority review designation to Lutathera as a treatment for patients with gastroenteropancreatic neuroendocrine tumors. The application was based upon data from the phase III NETTER-1 trial, which compared Lutathera with high-dose octreotide LAR for patients with grade 1 or 2 metastatic midgut NETs.

In this trial, there was a 79% reduction in the risk of progression or death with Lutathera compared with octreotide. Median PFS had not been reached in the Lutathera arm compared with 8.4 months in the high-dose octreotide arm (HR, 0.21; 95% CI, 0.13-0.33; P <.0001). Based on the Kaplan-Meier curve, the estimated median PFS was approximately 40 months with Lutathera.

The ORR with Lutathera was 18% versus 3% with octreotide (P = .0008). At the interim analysis of OS there was a 60% reduction in the risk of death seen with Lutathera versus octreotide (HR, 0.398; 95% CI, 0.21-0.77; P = .0043); however, the prespecified P value for statistical significance at the interim analysis was <.000085. The FDA is scheduled to make a decision on the PRRT by December 28, 2016, as part of the Prescription Drug User Fee Act.

See more http://www.onclive.com/web-exclusives/fda-grants-lutathera-priority-review-for-neuroendocrine-tumors

Ruxolitinib Granted Breakthrough Status for GVHD

The FDA has granted a breakthrough therapy designation to ruxolitinib for the treatment of patients with acute graft-versus-host disease. The designation was based on 2 small studies demonstrating high response rates with ruxolitinib in patients with GVHD. In the first study, the overall response rate was 81.5% in the steroid refractory (SR)-acute GVHD group and 85.4% in patients with SR-chronic GVHD.

Patients with SR-acute GVHD had a 6-month overall survival rate of 79% and the 6-month OS was 97.4% (95% CI, 92.3-100) in the SR-chronic GVHD arm. The second study looked at ruxolitinib in those with steroid dependent chronic GVHD. In this group, 10 patients were able to discontinue prednisone at a median of 72 days after starting ruxolitinib. Two patients reduced prednisone to physiologic doses and the other 4 patients were tapering prednisone at the time of the data analysis.

See more http://www.onclive.com/web-exclusives/fda-grants-ruxolitinib-breakthrough-designation-for-acute-gvhd

CRISPR Gene Therapy Advancing Toward Human Use

A team of researchers is seeking to use CRISPR gene editing technology for the first time in humans to create an engineered T-cell agent that would knock out the gene that controls the immune checkpoint’s activity. Plans for the complex therapy call for taking NY-ESO-1, a peptide-based form of adoptive immunotherapy already in clinical trials, and disrupting the activity of the PDCD1 gene that encodes PD-1 as well as the endogenous TRAC and TRBC genes, which control T-cell receptor alpha and beta, respectively.

The goal would be to enhance the immune response with NY-ESO-1 by eliminating genomic drivers that hamper T-cell proliferation and function. The Recombinant DNA Advisory Committee voted 12-0 with 1 abstention to support the study protocol, which now goes to the FDA for review. Panel members said they were enthusiastic about the science underlying the proposal but recommended that the protocol be strengthened to more fully disclose the risks to participants and to safeguard against financial conflicts of interest that UPenn may have in advancing the technology. The proposal marks an early clinical venture for the Parker Institute for Cancer Immunotherapy, a research collaborative funded by technology entrepreneur Sean Parker.

See more http://www.onclive.com/web-exclusives/firstinhuman-crispr-immunotherapy-would-target-pd1

CHMP Recommends Approval of Pembrolizumab for NSCLC

The EMA's Committee for Medicinal Products for Human Use has granted a positive opinion for use of pembrolizumab as a treatment for patients with locally advanced or metastatic PD-L1-positive non—small cell lung cancer following at least 1 chemotherapy regimen. The recommendation is based on data from the KEYNOTE-010 and KEYNOTE-001 trials. In KEYNOTE-010, the median OS was 10.4 months with the 2 mg/kg dose of pembrolizumab compared with 8.5 months with docetaxel in those with >1% PD-L1 expressing NSCLC (HR, 0.71; P = .0008).

With a larger dose of pembrolizumab (10 mg/kg), median OS was 12.7 months, representing a 39% reduction in the risk of death versus docetaxel (HR, 0.61; P <.0001). In the KEYNOTE-001 trial the ORR with pembrolizumab was 41% among a subgroup of 61 patients with pretreated PD-L1—positive advanced NSCLC. Receiving the positive opinion suggests pembrolizumab is likely to be approved for this indication in the EU when the European Commission issues its final decision, which is expected by the third quarter of 2016.

See more http://www.onclive.com/web-exclusives/chmp-recommends-approval-of-pembrolizumab-for-lung-cancer

Neratinib Submitted for European Approval

A marketing authorization application has been submitted to the European Medicines Agency for neratinib as a potential extended adjuvant therapy for patients with HER2-positive early stage breast cancer following 12 months of trastuzumab. The application was based on findings from the phase III ExteNET study in which extended treatment with neratinib demonstrated a 2-year disease-free survival rate of 93.9% compared with 91.6% in the placebo arm, representing a 33% improvement versus placebo.

In the United States, Puma plans to submit a new drug application to the FDA within the next few months. This action was anticipated earlier in the year; however, the FDA requested a new statistical analysis of the ExteNET trial that censored for patients who missed 2 or more scheduled disease assessments prior to recurrence or death. The NDA will also include data from a phase II study that explored prophylactic loperamide to prevent neratinib-associated diarrhea.

See more http://www.onclive.com/web-exclusives/ema-approval-sought-for-neratinib-in-her2-breast-cancer