ANTITUMOR ACTIVITY OF PEMBROLIZUMAB PLUS DINACICLIB IN PATIENTS WITH DIFFUSE LARGE B CELL LYMPHOMA: THE PHASE 1B KEYNOTE-155 STUDY

Introduction: KEYNOTE-155 (NCT02684617) evaluated the antitumor activity of pembrolizumab (pembro) plus dinaciclib in patients (pts) with relapsed/refractory (rr) CLL, MM, and DLBCL. Here we present data from an interim analysis of safety and efficacy in pts with rrDLBCL. Methods: In this phase 1b, two-part, non-randomized, open-label study, pts with rrDLBCL who received ≥2 prior therapies were enrolled into a dose-evaluation phase (two 21-day [d] cycles of pembro 200 mg [d1] and dinaciclib 7 mg/m2 [d1], 10 mg/m2 [d8] in cycle 1 and 14 mg/m2 [d1, d8] from cycle 2 onwards). The DLBCL expansion cohort was opened for the signal-detection phase (≥30 patients) if ≤4 pts had dose-limiting toxicities (DLTs) during dose-evaluation. Treatment continued up to 35 cycles or until progression (PD) or unacceptable toxicity. Response was assessed every 3 cycles for DLBCL (Revised Response Criteria for Malignant Lymphoma 2007). Pts who discontinued before PD were followed Q12W until PD, new anticancer treatment, or death. The primary endpoint was safety and tolerability. Secondary endpoints included ORR by investigator, DOR, PFS, and OS. Efficacy and safety were assessed in all pts who received ≥1 dose of pembrolizumab or dinaciclib. Results: As of Apr 25, 2018, 38 pts with rrDLBCL were enrolled and treated. Median age was 64.5 years (range, 39-85), 22 (58%) pts had ECOG PS 1, and 22 (58%) had ≥3 prior therapies. After median follow-up of 2.79 mo (range, 1.5-6.8), 36 (95%) pts discontinued treatment: 21 (55%) PD, 12 (32%) by physician decision (10 [26%] clinical progression, 1[3%] logistics, 1 [3%] new therapy), 2 (5%) pt decision, and 1 (3%) AE. Median time on treatment was 51d (range, 1-471). Among 12 pts in all disease cohorts enrolled in the dose-evaluation phase, DLTs occurred in 1 of 6 (17%) evaluable pts (grade 4 thrombocytopenia) with rrDLBCL. Of 38 pts with rrDLBCL, 24 (63%) had a treatment-related AE. Common treatment-related AEs were decreased platelets (21%), lymphopenia (16%), nausea (13%), anemia (13%), diarrhea (13%), and pyrexia (13%). 12 (32%) pts had a grade 3-4 treatment-related AE. Common grade 3-4 treatment-related AEs were lymphopenia (13%), decreased neutrophils (11%), decreased platelets (8%), leukopenia (8%), and laboratory TLS (5%). There was no clinical TLS and no treatment-related deaths. ORR was 18% (95% CI, 8-34) (3 CR and 4 PR) and median DOR was 4.9 mo (range, 2.1-13.8); 2 pts were on treatment at data cutoff. With 36 (95%) events, median PFS was 2.1 mo (95% CI, 2-3) with 6-mo and 12-mo PFS of 13% and 8%, respectively. 19 (50%) pts died, with median OS of 9.8 mo (95% CI, 3 to not reached), and 12-mo OS of 43%. Conclusion: Despite limited overall response, the observed CRs and durability (up to 13 mo) provide proof of concept for activity of this combination in rrDLBCL and rationale for further studies to define optimal dosing of dinaciclib, given the brevity of CDK9 inhibition observed in preclinical models. Keywords: diffuse large B-cell lymphoma (DLBCL); PD-1L; Pembrolizumab. Disclosures: Gregory, G: Consultant Advisory Role: Advisory board member at Gilead; Honoraria: Roche; Research Funding: Amgen; Other Remuneration: Travel expenses from Roche. Walker, P: Research Funding: Merck & Co., Inc. Chang, J: Research Funding: Genentech, Celgene. Hernandez-Ilizaliturri, F: Consultant Advisory Role: Advisory board member for Celgene, Novartis, Amgen, Pharmacyclics, Pfizer, and Seattle Genetics. Klein, A: Consultant Advisory Role: Consultant for Shire; Honoraria: Takeda; Other Remuneration: Travel expenses from Takeda. Rybka, W: Consultant Advisory Role: Consultant for Merck & Co., Inc.; Honoraria: Merck & Co., Inc.; Research Funding: Merck & Co., Inc.; Other Remuneration: Travel expenses from Merck & Co., Inc. Wagner-Johnston, N: Consultant Advisory Role: Advisory board: JUNO, ADC therapeutics, Janssen; Research Funding: Merck & Co., Inc., Novartis, Celgene, ASTEX. Escobar, C: Other Remuneration: Speakers’ bureau: Kite; Gilead. Pagel, J: Consultant Advisory Role: Pharmacyclics; Gilead. Mohrbacher, A: Other Remuneration: Speakers’ bureau: Genetech; Takeda. Opat, S: Consultant Advisory Role: Roche, Janssen, Celgene, Takeda, Abbvie, Gilead, BMS, Merck, Sanofi; Honoraria: Roche, Janssen, Celgene, Takeda, Abbvie, Gilead, Mundipharma; Research Funding: Roche, Janssen, Celgene, Takeda, Novartis, Abbvie, Gilead, Amgen; Other Remuneration: Trial Support: Roche, Janssen, Celgene, Takeda, Abbvie, Beigene, Merck, Epizyme. Ma, H: Employment Leadership Position: Merck & Co., Inc.; Stock Ownership: Merck & Co., Inc. Gwo, J: Employment Leadership Position: Merck & Co., Inc.; Stock Ownership: Merck & Co., Inc. Farooqui, M: Employment Leadership Position: Merck & Co., Inc.; Stock Ownership: Merck & Co., Inc.