2. Academic Validation
  3. Safety and efficacy of quavonlimab, a novel anti-CTLA-4 antibody (MK-1308), in combination with pembrolizumab in first-line advanced non-small-cell lung cancer

Safety and efficacy of quavonlimab, a novel anti-CTLA-4 antibody (MK-1308), in combination with pembrolizumab in first-line advanced non-small-cell lung cancer

  • Ann Oncol. 2021 Mar;32(3):395-403. doi: 10.1016/j.annonc.2020.11.020.
R Perets 1,  J Bar 2,  D W Rasco 3,  M-J Ahn 4,  K Yoh 5,  D-W Kim 6,  A Nagrial 7,  M Satouchi 8,  D H Lee 9,  D R Spigel 10,  D Kotasek 11,  M Gutierrez 12,  J Niu 13,  S Siddiqi 14,  X Li 14,  J Cyrus 14,  A Chackerian 15,  A Chain 14,  R A Altura 14,  B C Cho 16
Affiliations

Affiliations

  • 1 Department of Oncology, Rambam Medical Center, Technion-Israel Institute of Technology, Haifa, Israel.
  • 2 Cancer Center, Chaim Sheba Medical Center at Tel HaShomer, Ramat Gan, and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
  • 3 Phase I, START, San Antonio, USA.
  • 4 Department of Medicine, Samsung Medical Center, Sungkyunkwan University of Medicine, Seoul, South Korea.
  • 5 Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
  • 6 Department of Hemato Oncology, Medical Oncology Center, and Personalized Cancer Medicine Center, Seoul National University Hospital, Seoul, South Korea.
  • 7 Department of Cancer and Hematology, Blacktown Hospital and University of Sydney, Sydney, Australia.
  • 8 Department of Thoracic Oncology, Hyogo Cancer Center, Akashi, Japan.
  • 9 Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
  • 10 Department of Medical Oncology, Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, USA.
  • 11 Department of Medical Oncology, Adelaide Cancer Centre and University of Adelaide, Kurralta Park, Australia.
  • 12 Department of Hematology, Hematology Oncology, and Medical Oncology, Hackensack University Medical Center, Hackensack, USA.
  • 13 Department of Medical Oncology, Banner MD Anderson Cancer Center, Gilbert, USA.
  • 14 MRL, Merck & Co., Inc., Kenilworth, NJ, Kenilworth, USA.
  • 15 Department of Discovery Oncology, Merck & Co., Inc., Kenilworth, USA.
  • 16 Division of Medical Oncology, Yonsei Cancer Center, Seoul, South Korea. Electronic address: CBC1971@yuhs.ac.
PMID: 33276076 DOI: 10.1016/j.annonc.2020.11.020
Abstract

Background: Quavonlimab (MK-1308), a novel anti-CTLA-4 antibody, in combination with pembrolizumab was investigated in a phase I study.

Patients and methods: Dose-escalation (DE) phase: patients with advanced/metastatic solid tumors received an initial flat dose of quavonlimab as monotherapy [25 mg (cohort 1), 75 mg (cohort 2), or 200 mg (cohort 3)] followed by four treatments of the same quavonlimab dose plus pembrolizumab every 3 weeks (Q3W). Dose-confirmation phase (DC): patients with stage IIIB/IV non-small-cell lung Cancer (NSCLC) received first-line quavonlimab [25 mg Q3W (arm A), 25 mg Q6W (arm B), 75 mg Q6W (arm C), or 75 mg Q3W (arm E)] plus pembrolizumab. Primary objectives were safety and tolerability and establishment of the recommended phase II dose (RP2D) of quavonlimab when used with pembrolizumab. Objective response rate (ORR) was a secondary endpoint. Efficacy based on PD-L1 expression, tumor mutational burden (TMB), and changes in circulating CD4+/CD8+ cells were exploratory endpoints.

Results: Thirty-nine patients were enrolled in DE [n = 14 (cohort 1); n = 17 (cohort 2); n = 8 (cohort 3)] and 134 in DC [n = 40 (arm A); n = 40 (arm B); n = 40 (arm C); n = 14 (arm E)]. Maximum-tolerated dose was not reached. Grade 3-5 treatment-related adverse events (AEs; graded according to NCI CTCAE v4.03) occurred in 0%, 23.5%, and 75.0% of patients in DE cohorts 1, 2, and 3, respectively, and 35.0%, 30.0%, 35.0%, and 57.1% of patients in DC arms A, B, C, and E, respectively. Efficacy was observed at all dose levels/schedules in patients with NSCLC. ORRs were 40.0% [95% confidence interval (CI), 24.9-56.7; arm A], 37.5% (95% CI, 22.7-54.2; arm B), 27.5% (95% CI, 14.6-43.9; arm C), and 35.7% (95% CI, 12.8-64.9; arm E). PD-L1 expression and total number of circulating CD4+ cells correlated with ORR.

Conclusions: Quavonlimab 25 mg Q6W plus pembrolizumab demonstrated similar efficacy and a better safety profile among all quavonlimab doses/schedules evaluated; this regimen was the chosen RP2D.

Keywords

CTLA-4; MK-1308; immunotherapy; non-small-cell lung cancer; pembrolizumab; quavonlimab.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-P99809
    ≥99.0%, anti-CTLA-4 antibody