Background: Pembrolizumab (pembro) is a monoclonal antibody against PD-1 that helps to restore antitumor immune surveillance. KEYNOTE-023 (NCT02036502) is a phase 1 dose-escalation study evaluating safety and efficacy of pembro in combination with lenalidomide (len) and low-dose dexamethasone (dex) in patients with RRMM.
Methods: Patients with RRMM who failed ≥ 2 prior therapies enrolled. Modified 3 + 3 design was used for dose determination with cohorts of 3-6 patients treated with pembro 2 mg/kg Q2W + len 10 mg or 25 mg on days 1-21 and dex 40 mg weekly, repeated every 28 days. After preliminary MTD/MAD identification, additional patients received pembro 200 mg Q2W + len and dex for dose confirmation. Upon final MTD, patients enrolled in the dose expansion phase. Treatment continued for 24 mo or until confirmed disease progression or unacceptable toxicity. Response evaluated monthly using IMWG 2006.
Results: 3 DLTs from the pembro 2 mg/kg, 25-mg len cohort were observed in 17 patients in the dose determination/confirmation phase: grade 3/grade 4 neutropenia, grade 3 pneumonia, and grade 3 tumor lysis syndrome with grade 4 hyperuricemia. Based on dose confirmation phase, pembro 200 mg + len 25 mg and dex 40 mg was the MTD/MAD. As of Sep 22, 2015, an additional 33 patients were enrolled in the expansion phase. Median age for the total population was 62 y, 72% had ≥ 3 prior therapies, 76% were refractory to len, and 30% had double refractory disease. 36 patients (72%) experienced treatment-related AEs, most commonly thrombocytopenia (28%) and neutropenia (24%). With a median follow-up of 9.7 mo (range, 4.3-18.4), 13/17 (76%) patients evaluated for efficacy in dose determination/confirmation responded to treatment, including 4 VGPRs (2 in len-refractory) and 9 PRs (3 in len-refractory), with median duration of response 9.7 mo (range, 0+-16.7+). 3 patients (18%) had stable disease. 94% had a reduction in M protein or free light chains. Updated efficacy data for all 50 patients will be presented.
Conclusions: Pembro in combination with len and dex was associated with a tolerable safety profile and promising antimyeloma activity in heavily pretreated patients with RRMM.