Abstract 1410P
Background
Vibostolimab, a humanized, antagonist monoclonal antibody, binds to the T-cell immunoreceptor with Ig and ITIM domains (TIGIT) and blocks its interaction with its ligands, CD112 and CD155. In the first-in-human, phase 1 dose-finding study (NCT02964013), vibostolimab monotherapy plus pembrolizumab was well tolerated, with a manageable safety profile across all doses tested in patients with advanced solid tumors in the dose-escalation/confirmation phase. Promising antitumor activity was observed in a heavily pretreated population across multiple tumor types. We present results of the dose-expansion/confirmation phase in patients with non–small cell lung cancer (NSCLC) naive to prior anti–PD-1/PD-L1 therapy (anti–PD-1/PD-L1-naive).
Methods
Patients with anti–PD-1/PD-L1-naive advanced NSCLC, regardless of PD-L1 status, received vibostolimab (200 or 210 mg) plus pembrolizumab (200 mg) on day 1 of each 3-week cycle for up to 35 cycles. Primary end points were safety and tolerability. Secondary and exploratory end points included ORR, DOR, and PFS based on investigator review per RECIST v1.1. Database cutoff was March 3, 2020.
Results
In the 41 patients enrolled with anti–PD-1/PD-L1-naive NSCLC, 73% had received ≥1 prior line of therapy. Median age was 62 years; 68% were male and 83% had an ECOG performance status of 1. Median follow-up was 11 months (range, 7-18). Treatment-related adverse events (TRAEs) occurred in 34 patients (83%); pruritus (34%), hypoalbuminemia (29%), and pyrexia (20%) were the most frequent (≥20%). Grade 3-4 TRAEs occurred in 6 patients (15%); no deaths due to TRAEs were reported. ORR and PFS are reported in the table. Median DOR for all patients was not reached (range, 4 to 17+ months). Table: 1410P
| All Patients N = 41 | TPS ≥1% n = 13 | TPS <1% n = 12 | |
| ORR, % (95% CI) | 29 (16-46) | 46 (19-75) | 25 (5-57) |
| Median PFS, months (95% CI) | 5.4 (2.1-8.2) | 8.4 (3.9-10.2) | 4.1 (1.9-NR) |
| 16 patients did not have available PD-L1 data. |
Conclusions
Vibostolimab in combination with pembrolizumab was well tolerated and demonstrated promising antitumor activity in patients with advanced NSCLC naive to anti–PD-1/PD-L1 therapy.
Clinical trial identification
NCT02964013.
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Holly C. Cappelli, PhD, CMPP, and Dana Francis, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
J. Niu: Honoraria (self): OncLive. A. Nagrial: Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Roche. M. Voskoboynik: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self): MSD. H.C. Chung: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck-Serono; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Honoraria (self): Foundation Medicine; Advisory/Consultancy, Research grant/Funding (institution): Taiho; Advisory/Consultancy: Celltrion; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy: Quintiles; Advisory/Consultancy: BMS; Advisory/Consultancy: Gloria; Advisory/Consultancy, Research grant/Funding (institution): Beigene; Advisory/Consultancy, Research grant/Funding (institution): Amgen; Advisory/Consultancy: Zymework; Research grant/Funding (institution): GSK; Research grant/Funding (institution): BMS/Ono. D.H. Lee: Honoraria (self): AbbVie; Honoraria (self): AstraZeneca; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): ChongKunDang; Honoraria (self): Eli Lilly; Honoraria (self): GreenCross Corp; Honoraria (self): Janssen; Honoraria (self): Menarini; Honoraria (self): Merck; Honoraria (self): MSD; Honoraria (self): Mundipharma; Honoraria (self): Novartis; Honoraria (self): Ono; Honoraria (self): Roche; Honoraria (self): St Cube; Travel/Accommodation/Expenses: Takeda; Travel/Accommodation/Expenses: BluePrint Medicine. M-J. Ahn: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Takeda; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Merck; Advisory/Consultancy: Ono; Advisory/Consultancy: BMS; Advisory/Consultancy: Novartis; Advisory/Consultancy: Alpha Pharmaceutical; Advisory/Consultancy: Roche; Advisory/Consultancy: Progeneer. T.M. Bauer: Advisory/Consultancy: Guardant Health, Loxo, Pfizer (Institution & personally), Exelixis, Blueprint Medicines, Foundation Medicine, Ignyta (Institution), Modern Therapeutics; Speaker Bureau/Expert testimony: Bayer; Research grant/Funding (institution): Daiichi Sankyo, Medacto, Inc., Incyte, Mirati Therapeutics, MedImmune, Abbive, AstraZeneca, Leap Therapeutics, MabVax, Streamline Therapeutics, Merck & Co., Inc., Eli Lilly, GSK, Novartis, Pfizer, Genentech/Roche, Deciphera, Merimack, Immunogen, Millenniu; Travel/Accommodation/Expenses: Astellas Pharma, AstraZeneca, Celgene, Clovis Oncology, EMD Serono, Genentech, Eli Lilly, Merck & Co., Inc., Novartis, Pharmacyclics, Sysmex, Pfizer; Full/Part-time employment: Tennessee Oncology. A. Jimeno: Shareholder/Stockholder/Stock options: Champions Oncology; Shareholder/Stockholder/Stock options: Suvica; Research grant/Funding (institution): Merck; Research grant/Funding (institution): AZ; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): Iovance; Research grant/Funding (institution): Moderna; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Holystone; Research grant/Funding (institution): SQZ; Research grant/Funding (institution): DebioPharm; Research grant/Funding (institution): Genocea. K.F. Mileham: Honoraria (self): Takeda; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bayer; Speaker Bureau/Expert testimony: Merck; Research grant/Funding (institution): Celgene. E. Chartash: Full/Part-time employment: Merck & Co., Inc. D. Chen: Full/Part-time employment: Merck & Co., Inc. J. Healy: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc. M. Rajasagi: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc. C. Maurice-Dror: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Medison. All other authors have declared no conflicts of interest.