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Poster Discussion session - Developmental therapeutics / investigational immunotherapy

4575 - Phase 1 Study of the CTLA-4 Inhibitor MK-1308 in Combination With Pembrolizumab in Patients With Advanced Solid Tumors


20 Oct 2018


Poster Discussion session - Developmental therapeutics / investigational immunotherapy


Clinical Research;  Immunotherapy

Tumour Site


Byoung Chul Cho


Annals of Oncology (2018) 29 (suppl_8): viii133-viii148. 10.1093/annonc/mdy279


B.C. Cho1, R. Perets2, J. Bar3, M. Ahn4, D. Kim5, K. Yoh6, A. Nagrial7, D.R. Spigel8, D.H. Lee9, M. Gutierrez10, D. Kotasek11, S. Siddiqi12, A. Chain12, B.D. Butts12, Y. Zhang12, X. Li12, J. Cyrus12, A. Tse12, R.A. Altura12, D. Rasco13

Author affiliations

  • 1 Medical Oncology, Yonsei Cancer Center Yonsei University, 6273 - Seoul/KR
  • 2 Oncology, Rambam Medical Center, Haifa/IL
  • 3 Institute Of Oncology, Sheba Medical Center at Tel HaShomer, 52621 - Ramat Gan/IL
  • 4 Hematology And Oncology, Samsung Medical Center, Sungkyunkwan University of Medicine, Seoul/KR
  • 5 Internal Medicine, Seoul National University Hospital, Seoul/KR
  • 6 Thoracic Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 7 Blacktown Cancer And Hematology Center, Blacktown Hospital and University of Sydney, Sydney/AU
  • 8 Medical Oncology, Sarah Cannon Research Institute, Nashville/US
  • 9 Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul/KR
  • 10 Oncology Research, Hackensack University Medical Center, Hackensack/US
  • 11 Medical Oncology, Adelaide Cancer Centre, 5037 - Adelaide/AU
  • 12 Medical Oncology, Merck & Co., Inc., Kenilworth/US
  • 13 Medical Oncology, START, San Antonio/US


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Abstract 4575


Targeting CTLA-4 and PD-1/L1 has been shown to be effective in selective solid tumors. MK-1308 is a novel humanized monoclonal antibody that binds CTLA-4 and blocks interaction with its ligands.


This ongoing, multicenter, multi-arm, open-label, phase 1b study will evaluate the safety, tolerability, PK/PD, and preliminary efficacy of MK-1308 in combination with pembrolizumab in patients (pts) with solid tumors (NCT03179436). In dose escalation, MK-1308 was given at either 25 mg or 75 mg (cohorts 1, 2) IV Q3W as monotherapy ×1 cycle, in combination with pembrolizumab 200 mg Q3W ×4 cycles, followed by pembrolizumab monotherapy. In dose confirmation, pts with first-line (1L) advanced NSCLC were treated with MK-1308 at 25 mg Q3W (arm A), 25 mg Q6W (arm B) or 75 mg Q6W (arm C), in combination with pembrolizumab 200 mg Q3W. Response was assessed Q9W.


A total of 47 pts were enrolled by Dec 31, 2017: 24 in dose escalation (cohort 1: 14; cohort 2: 11) and 22 in dose confirmation (arm A: 8; arm B: 9; arm C: 5). Median age was 61 years; 53% were male. MTD was not reached at any dose tested. Five DLTs were observed: 2 in cohort 2 (grade 3 rash), 1 in arm A (grade 4 hepatitis), 1 in arm B (grade 3 pneumonitis), and 1 in arm C (grade 3 enterocolitis). Treatment-related adverse events (TRAEs) were observed in 74% of pts. Most common (≥10%) were pruritus (23%), fatigue (17%), rash (17%), diarrhea (11%), and hyperthyroidism (11%), Grade 3/4 TRAEs were observed in 6 pts (12%). Discontinuation due to TRAE was observed in 5 pts. No pts had grade 5 TRAEs. Pharmacokinetics of MK-1308 were comparable to that of an approved CTLA-4 compound. Of the 21 evaluable 1L advanced NSCLC pts in dose confirmation who received at least 1 on-treatment assessment, there were 1 CR, 8 PR, 6 SD, and 6 PD. More mature data, inclusive of 140 pts (90 1L NSCLC) for ORR, DOR, and relationships between PD-L1, tumor mutation burden, and T-cell proliferation with ORR will be presented.


Preliminary results suggest that the combination of MK-1308 and pembrolizumab shows promising responses in a 1L advanced NSCLC population and manageable toxicity in most tumor types evaluated. Enrollment is ongoing.

Clinical trial identification

NCT03179436; trial initiation: June 7, 2017.

Legal entity responsible for the study

Merck & Co., Inc.


Merck & Co., Inc.

Editorial Acknowledgement

Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck & Co., Inc., Kenilworth, NJ, USA.


B.C. Cho: Advisory board: AstraZeneca, Boehringer Ingelheim, Roche, Yuhan, BMS, MSD, Novartis, Janssen, Ono; Speakers bureau: AstraZeneca, Novartis; Research funding: Bayer, AstraZeneca, Bayer, Janssen, Yuhan, Novartis, Champions Oncology, Ono, MOGAM, Dong-A ST; Honoraria: AstraZeneca, Boehringer Ingelheim, Roche, Yuhan, BMS, MSD, Novartis, Ono. R. Perets: Employment: Musli Thyropeutics; Honoraria: BMS. J. Bar: Advisory board member, Consultant fees: Roche, Boehringer Ingelheim, Novartis, BMS, MSD, Pfizer, AstraZeneca, Takada, Abbvie, VBL; Research funding: Boehringer Ingelheim, AstraZeneca, MSD M-J. Ahn: Advisory board: AstraZeneca, Lilly, Lyzz. K. Yoh: Research funding: MSD. A. Nagrial: Advisory board: MSD; Honoraria: MSD. D.H. Lee: Honoraria: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, CJ Healthcare, Eli Lilly, Janssen, Merck, MSD, Mundipharma, Novartis, Ono, Pfizer, Roche, Samyang Biopharm, ST Cube and Takeda. M. Gutierrez: Stock: Cota; Advisory board member: Eli Lilly, Esanex, Guardant 360; Speaker's bureau: Merck, BMS, Eli Lilly, Foundation Medicine. S. Siddiqi, A. Chain, B.D. Butts, Y. Zhang, X. Li, A. Tse: Employee and stockholder: Merck. J. Cyrus, R.A. Altura: Employee and stockholder: Merck; Travel expenses including accommodations: Merck. D. Rasco: Research funding: Merck. All other authors have declared no conflicts of interest.

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