Abstract 1400P
Background
Treatment with anti–T-cell immunoreceptor with Ig and ITIM domains (TIGIT) antibody, vibostolimab, as monotherapy or with pembrolizumab (pembro) demonstrated a manageable safety profile with promising antitumor activity in the dose-escalation/confirmation phase (part A) of the first-in-human, phase 1 study (NCT02964013) in heavily pretreated patients with advanced solid tumors. We present the results of the dose-confirmation/expansion phase, evaluating the safety and efficacy of vibostolimab and vibostolimab + pembro in patients with non–small cell lung cancer (NSCLC) whose disease progressed per RECIST v1.1 on prior anti–PD-1/PD-L1 therapy (anti–PD-1/PD-L1-refractory).
Methods
Patients with anti–PD-1/PD-L1-refractory NSCLC received vibostolimab (200 or 210 mg) monotherapy or vibostolimab (200 or 210 mg) + pembro (200 mg) on day 1 of each 3-week cycle for up to 35 cycles. Primary end points: safety and tolerability. Secondary and exploratory end points: ORR and DOR based on investigator review per RECIST v1.1. Data cutoff was March 3, 2020.
Results
Median follow up was 11 months (range, 5-16) for 79 patients with anti–PD-1/PD-L1–refractory NSCLC (n = 41, vibostolimab; n = 38 vibostolimab + pembro). Median age was 65 years, 60% were male, and 78% received ≥2 lines of prior therapy. Adverse events (AE) were reported in ≥97% and treatment-related AEs (TRAEs) in ≥65% of patients in both arms. The most common TRAEs (≥10% in either arm) were pruritus, fatigue, rash, arthralgia, and decreased appetite. Ten patients reported grade 3-4 TRAEs; the most common were lipase increase and hypertension. One patient in the vibostolimab + pembro arm died due to treatment-related pneumonitis. ORR (95% CI) was 7% (2-20) with vibostolimab monotherapy and 5% (<1-18) with vibostolimab + pembro. Median DOR was 9 months (range, 9 to 9) with vibostolimab monotherapy and 13 months (range, 4+ to 13) with vibostolimab + pembro.
Conclusions
Vibostolimab monotherapy and in combination with pembro was well tolerated and demonstrated modest antitumor activity in patients with advanced NSCLC refractory 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
M-J. Ahn: Honoraria (self): AstraZeneca, TAKEDA, Lilly, MSD, Merck; Advisory/Consultancy: AstraZeneca, TAKEDA, Lilly, MSD, ONO, BMS, Novartis, Alpha pharmaceutical, Roche, Progeneer, Merck. J. Niu: Honoraria (self): OncLive. D-W. Kim: Travel/Accommodation/Expenses: Amgen, Daiichi Sankyo; Research grant/Funding (institution): Alpha Biopharma, AstraZeneca/ MedImmune, Boehringer Ingelheim, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, Ono Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, and Yuhan. D. Rasco: Research grant/Funding (institution): Merck & Co., Inc. K.F. Mileham: Honoraria (self): Takeda; Advisory/Consultancy: AstraZeneca, Bayer; Speaker Bureau/Expert testimony: Merck; Research grant/Funding (institution): Celgene. H.C. Chung: Honoraria (self): Merck-Serono, Lilly, Foundation Medicine; Advisory/Consultancy: Taiho, Celltrion, MSD, Lilly, Quintiles, BMS, Merck-Serono, Gloria, Beigene, Amgen, Zymework; Research grant/Funding (institution): illy, GSK, MSD, Merck-Serono, BMS/Ono, Taiho, Amgen, Beigene. U.N. Vaishampayan: Advisory/Consultancy: Merck & Co., Inc.; Research grant/Funding (institution): Merck & Co., Inc. C. Maurice-Dror: Speaker Bureau/Expert testimony: BMS, MSD, Medison; Travel/Accommodation/Expenses: BMS, MSD, Medison. P. Lo Russo: Advisory/Consultancy: AbbVie, Agios, Five Prime, GenMab, Halozyme, Roche-Genentech, Genentech. CytomX, Takeda, SOTIO, Cybrexa, Agenus, Tyme, IQVIA, TRIGR, Pfizer, I-MAB, ImmunoMet, Black Diamond, Glaxo-Smith Kline, QED Therapeutics, AstraZeneca, EMD Serono, Shattuck, Astellas,; Research grant/Funding (institution): AbbVie, ADC Therapeutics, ALX Oncology, Inc, Astellas Pharma US, Inc, Astex Pharmaceuticals, Inc, AstraZeneca, Bayer Healthcare Pharmaceuticals, Inc, Boehringer Ingelheim Pharmaceuticals, Inc, Bristol-Myers Squibb Research & Development, Corvus Pharm. T. Golan: Advisory/Consultancy: AstraZeneca, AbbVie, Teva, Bayer, Merck/MSD; Speaker Bureau/Expert testimony: AbbVie, Bioline, Roche; Research grant/Funding (institution): AstraZeneca , Merck/MSD. E. Chartash: Full/Part-time employment: Merck & Co., Inc. D. Chen: Full/Part-time employment: Merck & Co., Inc. J. Healy: Full/Part-time employment: Merck & Co., Inc.; Shareholder/Stockholder/Stock options: Merck & Co., Inc. M. Rajasagi: Full/Part-time employment: Merck & Co., Inc.; Shareholder/Stockholder/Stock options: Merck & Co., Inc. D.H. Lee: Honoraria (self): AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, ChongKunDang, Eli Lilly, GreenCross Corp, Janssen, Menarini, Merck, MSD, Mundipharma, Novartis, Ono, Roche, ST Cube, Takeda; Travel/Accommodation/Expenses: Takeda, Blueprint Medicine.