Promising New Rare Cancer Drug Highlights Oncology News Roundup

Recent news in cancer drug development.

Recent news in cancer drug development.

Pembrolizumab Granted Breakthrough Status in mCRC

The FDA recently granted a breakthrough therapy designation to pembrolizumab as a potential therapy for patients with microsatellite instability-high metastatic colorectal cancer.

The designation was based on findings from an ongoing phase II study, which demonstrated high response rates with pembrolizumab in patients with heavily pretreated CRC with mismatch repair deficiency, a condition that causes MSI.

In the findings from the study presented at ASCO, the objective response rate was 62% with pembrolizumab in MMR-deficient mCRC compared with 0% in patients with MMR-proficient tumors. Median progression-free survival and overall survival were not reached, with many patients responding to treatment for longer than 12 months in the MMR-deficient arm.

OS and PFS were not reached in the MMR-deficient group versus a median PFS of 2.3 months (HR, 0.10; P <.001) and an OS of 7.6 months in the MMR-proficient group (HR, 0.22; P = .05). The phase II KEYNOTE-164 study is evaluating the effectiveness of MMR and MSI-H as a predictive marker in patients with pretreated mCRC.

This study is meant to support a regulatory filing for pembrolizumab in mCRC, if results are positive.

See more at: http://www.onclive.com/web-exclusives/pembrolizumab-granted-breakthrough-status-for-microsatellite-instability-high-mcrc

T-VEC Approved for Melanoma

The FDA approved the first-in-class oncolytic immunotherapy talimogene laherparepvec (T-VEC; Imlygic) for the treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery, based on results from the phase III OPTiM study.

Durable response rate was the primary endpoint of the pivotal trial, with overall survival as a secondary outcome measure. DRR was 16.3% with T-VEC compared with 2.1% for GM-CSF. At the primary survival analysis, the median OS was 23.3 months with T-VEC compared with 18.9 months for GM-CSF (HR, 0.79; P = .051).

This examination occurred after 290 events and was powered to detect an HR of 0.67, with a P value of .05 representing significance. In a subgroup analysis, differences in DRR were more pronounced in patients with stage IIIb/c melanoma (33% vs 0%).

Additionally, in the first-line setting, the DRR with T-VEC was 24% versus 0% with GM-CSF. Additionally, in the subgroup analysis, those with stage IIIb/c or IVM1a melanoma experienced a 43% reduction in the risk of death with T-VEC (HR, 0.57; 95% CI, 0.40-0.80; P <.001). For this group, the median OS with T-VEC (n = 163) was 41.1 versus 21.5 months with GM-CSF (n = 86).

See more at: http://www.onclive.com/web-exclusives/fda-approves-t-vec-for-advanced-melanoma

FDA Approves Adjuvant Ipilimumab for Melanoma

The FDA expanded the approval of ipilimumab to include adjuvant treatment of patients with stage III melanoma with pathologic involvement of regional lymph nodes >1 mm who have undergone complete resection including total lymphadenectomy.

The approval was based on results from the phase III EORTC 18071 trial, in which adjuvant ipilimumab at a 10 mg/kg dose reduced the risk of recurrence by 25% versus placebo (HR, 0.75; P <.002). The drug was approved at this 10 mg/kg dose, which is higher than the 3 mg/kg dose the FDA recommended in ipilimumab's initial approval for advanced melanoma.

The median recurrence-free survival was 26.1 versus 17.1 months with ipilimumab and placebo, respectively. The 3-year RFS rate was 46.5% in the ipilimumab arm compared with 34.8% in the placebo group. The FDA included a boxed warning with the label for adjuvant ipilimumab, due to the potential for fatal immune-mediated adverse events and "unusual severe side effects," according to the regulatory agency.

See more at: http://www.onclive.com/web-exclusives/fda-approves-adjuvant-ipilimumab-in-melanoma

Olaparib Shows Promise in mCRPC With DNA-Repair Defects

Findings from the phase II TOPARP-A trial exploring olaparib in prostate cancer were recently published in the New England Journal of Medicine. Results were initially presented earlier in the year at the 2015 AACR Annual Meeting.

In the study, olaparib showed an overall response rate of nearly 90% in a biomarker-defined subgroup of patients with metastatic castration-resistant prostate cancer who had DNA-repair defects. Using NGS, the researchers discovered that 16 of 49 (33%) patients had homozygous deletions, deleterious mutations, or both in DNA-repair genes.

Fourteen of these 16 (88%) patients (labeled as “biomarker-positive”) responded to olaparib. Overall survival was also prolonged in the biomarker-positive group, with a median OS of 13.8 months compared with 7.5 months in the biomarker-negative group (P = .05).

Across all 49 evaluable patients who received at least one dose of olaparib, ORR was 33% (n = 16). At a median follow-up of 14.4 months, median OS was 10.1 months.

See more at: http://www.onclive.com/web-exclusives/olaparib-demonstrates-high-response-in-mcrpc-with-dna-repair-defects

Pexidartinib Receives Breakthrough Designation for Rare Disorder

The FDA granted a breakthrough therapy designation to pexidartinib (formerly PLX3397) as a potential therapy for patients with tenosynovial giant cell tumor for which surgical removal is contraindicated. The designation was based on findings from a phase I study, which were published in The New England Journal of Medicine.

In an expansion cohort of the study, the objective response rate with pexidartinib was 52.2% (95% CI, 32-73). Additionally, 30.4% of patients treated with pexidartinib had stable disease, for a disease control rate of 83% (95% CI, 67-98).

At the time of the analysis, the median progression-free survival had not been reached, with 17 patients remaining on the study, 7 of which had received pexidartinib for longer than 12 months. Responses seen with pexidartinib were significantly better than traditionally experienced by patients treated with imatinib.

In previous studies, imatinib has demonstrated an objective response rate of 19%. There currently are not any FDA-approved therapies specifically for TGCT.

The phase III ENLIVEN is currently enrolling participants and will compare pexidartinib with placebo. If positive, findings from this study will be submitted to the FDA. The estimated completion date is March 2018.

See more at: http://www.onclive.com/web-exclusives/fda-grants-pexidartinib-breakthrough-status-for-tenosynovial-giant-cell-tumor