Recent advances and updates in oncology and cancer drug development.
Rolling submission of a new drug application for brigatinib has been initiated for patients with advanced ALK-positive non—small cell lung cancer who are resistant to prior crizotinib. The rolling submission, which was allowed as part of a breakthrough therapy designation that was received in October 2014, is based on findings from the ongoing phase II ALTA trial.
The confirmed objective response rate for brigatinib at 180 mg daily was 54% and the median progression-free survival was 12.9 months. When considering stable disease rates, the disease control rate was 86%. The 1-year OS rate was 80%. In those with measurable active brain metastases, the intracranial ORR was 67% and the intracranial DCR was 83%. The company plans to complete the rolling submission within the third quarter of 2016, according to a statement.
The FDA will assign a review timeline within 60 days, once the submission is complete. Ariad has requested a priority review from the FDA, under which the agency would render a decision within 6 months rather than 10 months for a standard review.
Frontline pembrolizumab improved overall survival versus chemotherapy in patients with non—small cell lung cancer with high levels of PD-L1 expression, according to results from the phase III KEYNOTE-024 trial. The trial only included patients with high levels of PD-L1 expression on their tumors, defined as ≥50% as measured by a central laboratory with an immunohistochemistry assay.
Pembrolizumab was also shown to extend progression-free survival in the first-line NSCLC setting. Based on the findings, an independent panel recommended that the trial be halted and that patients in the chemotherapy arm be allowed to cross over and receive pembrolizumab. The safety data for pembrolizumab in KEYNOTE-024 were similar to previously reported outcomes with the PD-1 inhibitor in advanced NSCLC.
Merck intends to submit the complete results from the study at an upcoming medical conference. In previous findings from the phase I KEYNOTE-001 study, treatment-naive patients with PD-L1 expression ≥50% had an ORR of 50% with pembrolizumab (95% CI, 24.7-75.3). The PFS was 12.5 months (95% CI, 2.4-12.5) and the median OS was not yet reached.
Treatment with the PI3K-delta and gamma inhibitor duvelisib demonstrated an overall response rate of 46% for patients with indolent non-Hodgkin lymphoma, which successfully met the primary endpoint for the phase II DYNAMO study but not investor expectations. The phase II study enrolled 129 patients with iNHL, which included follicular lymphoma (n = 83), small lymphocytic leukemia (n = 28), and marginal zone lymphoma (n = 18).
The ORRs in each of these groups, respectively, were 41%, 68%, and 33%. Expectations for duvelisib in the DYNAMO study were set by the performance of the PI3K-delta inhibitor idelalisib, which was approved as a single-agent for patients with iNHL in July 2014. This approval was based on findings from a single-arm phase II study, in which single-agent idelalisib showed an ORR of 54% for patients with follicular lymphoma and 58% for those with SLL.
Based upon the DYNAMO results, the long-term outlook for the duvelisib was adjusted, studies exploring the agent in combination with venetoclax were paused, and 21% of the Infinity’s workforce was laid off as part of a research and development restructuring.
The European Commission approved obinutuzumab for use in combination with bendamustine, followed by maintenance obinutuzumab, as a treatment for patients with follicular lymphoma who are refractory to or progress on a single-agent rituximab or rituximab-containing regimen. The approval was based on findings from the phase III GADOLIN study, in which obinutuzumab plus bendamustine followed by obinutuzumab monotherapy reduced the risk of disease progression by 52% compared with bendamustine alone in patients with follicular lymphoma who progressed on rituximab-based therapy (HR, 0.48; P <.0001).
The median PFS, as determined by an independent panel, was not reached in the obinutuzumab arm versus 13.8 months in the control arm. By investigator assessment, the median PFS with obinutuzumab was 29.2 versus 13.7 months with bendamustine alone (HR, 0.48; P <.0001). At a median follow-up of 24.1 months, the risk of death was reduced by 38% with the obinutuzumab regimen compared with bendamustine alone (HR, 0.62; 95% CI, 0.39-0.98). Neither study arm has reached median OS.
The National Institute for Health and Care Excellence has approved the combination of nivolumab and ipilimumab for patients with metastatic melanoma, which allows the combination to be used within the National Health Service. The decision arrived just 2 months following a positive recommendation from the Committee for Medicinal Products for Human Use and 1 month following an approval from the European Commission. The decision was based upon a collection of data from the CheckMate-067 and -069 studies.
In CheckMate-067, the combination demonstrated a 58% reduction in the risk of progression or death versus ipilimumab monotherapy in previously untreated patients with advanced melanoma (HR, 0.42; 99.5% CI, 0.32-0.56; P <.0001). The objective response rate with the combination was 58% versus 19% with ipilimumab. The median duration of response with the combination was not yet met.
In the phase II study, The ORR was 61% with the combination versus 11% with ipilimumab alone in patients with BRAF wild-type advanced melanoma. The estimated 12-month overall survival rate with the combination was 79% versus 62% with ipilimumab alone. At 18 months, the OS rate was 73% with the combination versus 56% with ipilimumab.