J Niu1, C Maurice-Dror2, D H Lee3, D-W Kim4, A Nagrial5, M Voskoboynik6, H C Chung7, K Mileham8, U Vaishampayan9, D Rasco10, T Golan11, T M Bauer12, A Jimeno13, V Chung14, E Chartash15, M Lala16, Q Chen17, J A Healy15, M-J Ahn18. 1. Medical Oncology, Banner MD Anderson Cancer Center, Gilbert, USA. Electronic address: jiaxin.niu@bannerhealth.com. 2. Medical Oncology Division, Rambam Health Care Campus, Haifa, Israel. 3. Department of Oncology, Asan Medical Center, Seoul, South Korea. 4. Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, South Korea. 5. Medical Oncology, Blacktown Hospital, Blacktown, Australia; Medical Oncology, University of Sydney, Sydney, Australia. 6. Alfred Health and Monash University, Melbourne, Australia. 7. Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea. 8. Levine Cancer Institute, Atrium Health, Charlotte, USA. 9. Oncology/Internal Medicine, Karmanos Cancer Center, Detroit, USA. 10. START Center for Cancer Care, San Antonio, USA. 11. The Oncology Institute, Sheba Medical Center at Tel-Hashomer, Tel Aviv University, Tel Aviv, Israel. 12. Drug Development, Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, USA. 13. Medicine, University of Colorado, Anschutz Cancer Pavilion, Aurora, USA. 14. Medical Oncology, City of Hope National Medical Center, Duarte, USA. 15. Oncology Early Development, Merck & Co., Inc., Kenilworth, NJ, USA. 16. OED-QP2IO, Merck & Co., Inc., Kenilworth, NJ, USA. 17. BARDS, Merck & Co., Inc., Kenilworth, NJ, USA. 18. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Abstract
BACKGROUND: In this first-in-human phase 1 study (NCT02964013; MK-7684-001), we investigated the safety and efficacy of the anti-TIGIT (T cell immunoglobulin and ITIM domain) antibody vibostolimab as monotherapy or in combination with pembrolizumab. PATIENTS AND METHODS: Part A enrolled patients with advanced solid tumors, and part B enrolled patients with non-small-cell lung cancer (NSCLC). Patients received vibostolimab 2.1-700 mg alone or with pembrolizumab 200 mg in part A and vibostolimab 200 mg alone or with pembrolizumab 200 mg in part B. Primary endpoints were safety and tolerability. Secondary endpoints included pharmacokinetics and objective response rate (ORR) per RECIST v1.1. RESULTS: Part A enrolled 76 patients (monotherapy, 34; combination therapy, 42). No dose-limiting toxicities were reported. Across doses, 56% of patients receiving monotherapy and 62% receiving combination therapy had treatment-related adverse events (TRAEs); grade 3-4 TRAEs occurred in 9% and 17% of patients, respectively. The most common TRAEs were fatigue (15%) and pruritus (15%) with monotherapy and pruritus (17%) and rash (14%) with combination therapy. Confirmed ORR was 0% with monotherapy and 7% with combination therapy. In part B, 39 patients had anti-PD-1 (programmed cell death protein 1)/PD-L1 (programmed death-ligand 1)-naive NSCLC (all received combination therapy), and 67 had anti-PD-1/PD-L1-refractory NSCLC (monotherapy, 34; combination therapy, 33). In patients with anti-PD-1/PD-L1-naive NSCLC: 85% had TRAEs-the most common were pruritus (38%) and hypoalbuminemia (31%); confirmed ORR was 26%, with responses occurring in both PD-L1-positive and PD-L1-negative tumors. In patients with anti-PD-1/PD-L1-refractory NSCLC: 56% receiving monotherapy and 70% receiving combination therapy had TRAEs-the most common were rash and fatigue (21% each) with monotherapy and pruritus (36%) and fatigue (24%) with combination therapy; confirmed ORR was 3% with monotherapy and 3% with combination therapy. CONCLUSIONS: Vibostolimab plus pembrolizumab was well tolerated and demonstrated antitumor activity in patients with advanced solid tumors, including patients with advanced NSCLC.
BACKGROUND: In this first-in-human phase 1 study (NCT02964013; MK-7684-001), we investigated the safety and efficacy of the anti-TIGIT (T cell immunoglobulin and ITIM domain) antibody vibostolimab as monotherapy or in combination with pembrolizumab. PATIENTS AND METHODS: Part A enrolled patients with advanced solid tumors, and part B enrolled patients with non-small-cell lung cancer (NSCLC). Patients received vibostolimab 2.1-700 mg alone or with pembrolizumab 200 mg in part A and vibostolimab 200 mg alone or with pembrolizumab 200 mg in part B. Primary endpoints were safety and tolerability. Secondary endpoints included pharmacokinetics and objective response rate (ORR) per RECIST v1.1. RESULTS: Part A enrolled 76 patients (monotherapy, 34; combination therapy, 42). No dose-limiting toxicities were reported. Across doses, 56% of patients receiving monotherapy and 62% receiving combination therapy had treatment-related adverse events (TRAEs); grade 3-4 TRAEs occurred in 9% and 17% of patients, respectively. The most common TRAEs were fatigue (15%) and pruritus (15%) with monotherapy and pruritus (17%) and rash (14%) with combination therapy. Confirmed ORR was 0% with monotherapy and 7% with combination therapy. In part B, 39 patients had anti-PD-1 (programmed cell death protein 1)/PD-L1 (programmed death-ligand 1)-naive NSCLC (all received combination therapy), and 67 had anti-PD-1/PD-L1-refractory NSCLC (monotherapy, 34; combination therapy, 33). In patients with anti-PD-1/PD-L1-naive NSCLC: 85% had TRAEs-the most common were pruritus (38%) and hypoalbuminemia (31%); confirmed ORR was 26%, with responses occurring in both PD-L1-positive and PD-L1-negative tumors. In patients with anti-PD-1/PD-L1-refractory NSCLC: 56% receiving monotherapy and 70% receiving combination therapy had TRAEs-the most common were rash and fatigue (21% each) with monotherapy and pruritus (36%) and fatigue (24%) with combination therapy; confirmed ORR was 3% with monotherapy and 3% with combination therapy. CONCLUSIONS: Vibostolimab plus pembrolizumab was well tolerated and demonstrated antitumor activity in patients with advanced solid tumors, including patients with advanced NSCLC.
Authors: Sophie Rovers; Annelies Janssens; Jo Raskin; Patrick Pauwels; Jan P van Meerbeeck; Evelien Smits; Elly Marcq Journal: Biomedicines Date: 2022-03-14