Abstract CT557: Phase 1/2 study of quavonlimab (Qmab) + pembrolizumab (pembro) in patients (pts) with advanced melanoma that progressed on a PD-1/PD-L1 inhibitor
Authors: Deva Sanjeev , Mackiewicz Jacek , Dalle Stephane , Gogas Helen , Lugowska Iwona , Berrocal Alfonso , Menzies Alexander M. , Maio Michele , Nagrial Adnan , Eizmendi Karmele Mujika , Grob Jean-Jacques , Caglevic Christian , Lyle Megan , Martin-Liberal Juan , Altura Rachel , Ren Yixin , Khilnani Anuradha , Cyrus Jobin , Siddiqi Shabana , Lotem Michal 
Published: June 2022

Abstract
Background: Safe, effective treatment options for advanced melanoma that progressed on a PD-1/PD-L1 inhibitor is an unmet medical need. Results of the phase 1b KEYNOTE-029 trial showed promising antitumor activity in advanced melanoma with pembro combined with a CTLA-4 inhibitor. This ongoing, open-label, multiarm phase 1/2 study (NCT03179436) evaluating the CTLA-4 inhibitor Qmab + pembro showed antitumor activity as first-line treatment for advanced NSCLC and for previously treated extensive-stage SCLC. Data from the efficacy expansion phase in pts with advanced melanoma that progressed on a PD-1/PD-L1 inhibitor are presented.
Methods: Pts with unresectable stage III-IV melanoma and confirmed progressive disease (PD) per iRECIST within 12 wk of the last dose of a PD-1/PD-L1 inhibitor given alone or in combination for ≥2 doses (combinations with CTLA-4 inhibitors were not allowed) were randomly assigned (1:1) to receive Qmab 25 mg IV Q6W with or without pembro 400 mg IV Q6W; 100 pts in the Qmab + pembro arm and 40 pts in the Qmab monotherapy arm were planned for enrollment. Treatment in both arms was given for up to 18 cycles (~2 y) or until PD, toxicity, or pt withdrawal. Pts who had PD after ≥2 Qmab monotherapy cycles could crossover to Qmab + pembro. Tumor imaging was assessed Q9W to wk 54 and Q12W thereafter. Primary end points were safety and ORR by BICR per RECIST v1.1. Secondary and exploratory end points included DOR and PFS by BICR per RECIST v1.1 and OS.
Results: 151 pts were enrolled (n = 111, Qmab + pembro; n = 40, Qmab monotherapy); median time from first dose to database cutoff was 7.7 mo. In all pts, median age was 64 y; 66% of pts were male, 33% had BRAF-mutant tumors, and 50% had elevated LDH. Treatment-related adverse events (TRAEs) were reported in 87 pts (78%) in the Qmab + pembro arm and 24 pts (60%) in the Qmab monotherapy arm; grade 3/4 TRAEs were reported in 16 pts (14%) and 3 pts (8%), respectively. The most common TRAEs were pruritus (26%), fatigue (14%), diarrhea (14%), and rash (13%). No treatment-related deaths occurred in either arm; 5% of pts discontinued because of TRAEs. Confirmed ORR was 9% (95% CI, 4.4-15.9) with Qmab + pembro (1 CR, 9 PRs) and 3% (95% CI, 0.1-13.2) with Qmab monotherapy (1 PR). Median DOR was not reached (NR; range, 2.0+ to 13.8+ mo) with Qmab + pembro. DOR was 1.9+ with Qmab monotherapy. Median PFS was 2.1 mo (95% CI, 2.1-3.2) with Qmab + pembro and 2.1 mo (95% CI, 2.1-2.5) with Qmab monotherapy; 6-mo PFS rates were 21% and 13%, respectively. Median OS was NR (95% CI, 11.2 mo to NR) with Qmab + pembro and 7.8 mo (95% CI, 6.3 to NR) with Qmab monotherapy; 6-mo OS rates were 74% and 73%, respectively.
Conclusions: Qmab + pembro was generally well tolerated and provided modest antitumor activity in pts with advanced melanoma that progressed on a PD-1/PD-L1 inhibitor. This combination and a coformulation of Qmab + pembro will be further investigated in the KEYMAKER-U02 study.
Citation Format: Sanjeev Deva, Jacek Mackiewicz, Stephane Dalle, Helen Gogas, Iwona Lugowska, Alfonso Berrocal, Alexander M. Menzies, Michele Maio, Adnan Nagrial, Karmele Mujika Eizmendi, Jean-Jacques Grob, Christian Caglevic, Megan Lyle, Juan Martin-Liberal, Rachel Altura, Yixin Ren, Anuradha Khilnani, Jobin Cyrus, Shabana Siddiqi, Michal Lotem. Phase 1/2 study of quavonlimab (Qmab) + pembrolizumab (pembro) in patients (pts) with advanced melanoma that progressed on a PD-1/PD-L1 inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT557.