FDA Grants Pembrolizumab Breakthrough Status for Hodgkin Lymphoma

The designation was based on phase Ib data from the KEYNOTE-013 study and yet unpublished findings from the phase II KEYNOTE-087 trial. In data from the phase Ib study presented at the 2015 ASH Annual Meeting,¹pembrolizumab demonstrated an objective response rate (ORR) of 64.5% in pretreated patients with cHL.

Findings from KEYNOTE-087 will be presented at an upcoming medical meeting, according to Merck. In the study, pembrolizumab was administered to patients with relapsed/refractory classical Hodgkin lymphoma at 200 mg every 3 weeks across a variety of settings. The primary endpoint of the study was ORR (NCT02453594).

“The FDA’s breakthrough designation for this blood cancer provides an important mechanism to assist us in bringing this immunotherapy to patients who could benefit from its use,” Roger M. Perlmutter, MD, PhD, president, Merck Research Laboratories, said in a statement.

In the phase Ib study, patients at a median age of 32 years received pembrolizumab at 10 mg/kg every 2 weeks for up to 2 years. Sixty-eight percent of patients had received ≥4 prior lines of therapy and 71% had failed prior autologous stem cell transplantation (ASCT). All patients had progressed on prior brentuximab vedotin (Adcetris).

The ORR of 64.5% included 5 complete responses (16.1%) and 15 partial responses (48.4%). Additionally, 23% of patients experienced stable disease with pembrolizumab. After a median of 9.7 months of follow-up, median duration of response was not yet reached (range, 0-13.4+ months), with most responses (n = 14) ongoing at the time of the analysis. At the data cutoff, 45% of patients remained on therapy.

The most common treatment-related all-grade adverse events (AEs) were hypothyroidism (16%), diarrhea (13%), nausea (13%), and pneumonitis (10%). Five patients had grade 3 AEs; however, no grade 4 events or treatment-related deaths occurred. Altogether, 2 patients (6%) discontinued therapy due to AEs.

Initial findings from the KEYNOTE-013 study were presented at the 2014 ASH Annual Meeting.²In this report, which included data from 29 patients with cHL, more specifics were provided on response by previous treatment. In patients who failed prior ASCT (n = 20), the ORR was 75% with pembrolizumab, which included 4 complete responses and 11 partial responses. For the whole population the ORR was 66%.

“These early data presented at ASH 2014 are very promising,” lead investigator Craig Moskowitz, MD, clinical director, division of hematologic oncology, Memorial Sloan Kettering Cancer Center, said in a statement when the data were presented. “There are few options for patients with multiple relapsed or refractory, classical Hodgkin lymphoma, and pembrolizumab should continue to be studied for the treatment of this cancer.”

A phase III study is planned to compare pembrolizumab with brentuximab vedotin for patients with relapsed or refractory cHL. This study, labeled KEYNOTE-204, will evaluate pembrolizumab at the 200 mg every 3-week dose. The primary endpoints of the study, which hopes to enroll 300 participants, are progression-free survival and overall survival (NCT02684292).

This is the fourth breakthrough designation received by pembrolizumab. The agent has also received the designation for advanced melanoma, non—small cell lung cancer (NSCLC), and colorectal cancer. Currently, pembrolizumab is approved as a therapy for patients with melanoma and for those with PD-L1–positive NSCLC.

References

1. Armand P, Shipp MA, Ribrag V, et al. PD-1 Blockade with Pembrolizumab in Patients with Classical Hodgkin Lymphoma after Brentuximab Vedotin Failure: Safety, Efficacy, and Biomarker Assessment. Presented at: 57th American Society of Hematology Annual Meeting; Orlando, Florida; December 5-8, 2015. Abstract 680.
2. Moskowitz CH, Ribrag V, Michot JM, et al. PD-1 blockade with the monoclonal antibody pembrolizumab (MK-3475) in patients with classical Hodgkin lymphoma after brentuximab vedotin failure: preliminary results from a phase 1b study (KEYNOTE-013). Presented at: 56th Annual Meeting of the American Society of Hematology; December 5-9, 2014; San Francisco, California. Abstract 290.