The FDA accepted and granted priority review to a supplemental biologics license application for pembrolizumab as monotherapy for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma.
The FDA has accepted and granted priority review to a supplemental biologics license application (sBLA) for pembrolizumab (Keytruda) as monotherapy for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL), according to Merck, the developer of the agent.1
The sBLA was based on data from the pivotal, randomized, open-label, phase 3 KEYNOTE-204 trial, which is evaluating pembrolizumab monotherapy versus brentuximab vedotin (BV; Adcetris), a current standard of care for this patient population, for the treatment of patients with relapsed or refractory cHL.
A prescription drug user fee act (PDUFA) date of October 30, 2020 has been set by the FDA.
“Classical Hodgkin lymphoma accounts for more than 9 in 10 cases of Hodgkin lymphoma, which impacts approximately 7400 patients a year in the US. For patients with classical Hodgkin lymphoma who do not achieve remission after first-line treatment, there is a particularly poor prognosis due to the limited options available,” Jonathan Cheng, MD, vice president of oncology clinical research at Merck Research Laboratories, said in a press release. “We look forward to working with the FDA to bring [pembrolizumab] to more patients with classical Hodgkin lymphoma after initial treatment.”
The dual primary end points of the trial are progression-free survival (PFS) and overall survival (OS). Key secondary end points include objective response rate (ORR), complete remission rate (CRR), and safety. Overall, 304 patients were enrolled and 300 were treated with either 200 mg of pembrolizumab intravenously (IV) on day 1 of each 3-week cycle for up to 35 cycles or 1.8 mg/kg of BV intravenously on day 1 of each 3-week cycle for up to 35 cycles with a maximum of 180 mg per dose.
The median treatment duration (range) was 305.0 (range, 1-814) and 146.5 (range, 1-794) days with pembrolizumab and BV, respectively.2 A statistically significant improvement in primary PFS was observed with pembrolizumab vs BV (HR 0.65; 95% CI, 0.48-0.88; P = 0.00271], as well as median PFS (13.2 vs 8.3 months, respectively) and 12-month PFS (53.9% vs 35.6%).
Moreover, a significant improvement in PFS-secondary was observed with pembrolizumab vs BV (HR 0.62 [95% CI 0.46-0.85]; median 12.6 vs 8.2 months). Per investigator assessment, PFS was longer with pembrolizumab vs BV (HR 0.49 [95% CI 0.36-0.67]; median 19.2 vs 8.2 months). Further, the ORR was 65.6% for pembrolizumab and 54.2% for BV, while CRR rates were 24.5% and 24.2%, respectively.
The median duration of response (DOR) was 20.7 months (range, 0.0+ to 33.2+) for pembrolizumab and 13.8 months (range, 0.0+ to 33.9+) for BV. Grade 3-5 treatment related adverse events (TRAEs) occurred in 19.6% of patients receiving pembrolizumab and 25.0% with BV. One death due to a TRAE of pneumonia occurred with pembrolizumab.
However, according to the pre-specified analysis plan, the other dual primary endpoint of OS has not yet been formally tested. Therefore, the study will continue to evaluate OS.
The phase 3 trial also serves as the confirmatory trial for the pembrolizumab accelerated approval hematology indications. Merck is evaluating pembrolizumab across hematologic malignancies through a broad clinical program, including 3 registrational trials in cHL and primary mediastinal large B-cell lymphoma and more than 60 investigator-initiated studies across 15 tumors.
Data from the KEYNOTE-204 trial were recently presented at the 2020 American Society of Clinical Oncology Annual Meeting.
1. FDA Grants Priority Review to Merck’s Supplemental Biologics License Application for KEYTRUDA® (pembrolizumab) for Second-Line Treatment of Patients With Relapsed or Refractory Classical Hodgkin Lymphoma [news release]. Kenilworth, NJ. Published July 9, 2020. mrknewsroom.com/newsroom/news-releases/news-details/2020/FDA-Grants-Priority-Review-to-Mercks-Supplemental-Biologics-License-Application-for-KEYTRUDA-pembrolizumab-for-Second-Line-Treatment-of-Patients-With-Relapsed-or-Refractory-Classical-Hodgkin-Lymphoma/default.aspx. Accessed July 9, 2020.
2. Kuruvilla j, Ramchandren R, Santoro A, et al. KEYNOTE-204: Randomized, open-label, phase III study of pembrolizumab (pembro) versus brentuximab vedotin (BV) in relapsed or refractory classic Hodgkin lymphoma (R/R cHL). Journal of Clinical Oncology. doi: 10.1200/JCO.2020.38.15.