Abstract 991P
Background
Dostarlimab is a humanized programmed death 1 (PD-1) receptor monoclonal antibody that blocks interaction with the ligands PD-L1 and PD-L2. GARNET is a phase I study assessing antitumor activity and safety of dostarlimab monotherapy in patients with solid tumors. Here we report TRAEs across cohort A1 (mismatch repair–deficient [dMMR] endometrial cancer [EC]), cohort A2 (mismatch repair–proficient [MMRp] EC), cohort E (non–small cell lung cancer [NSCLC]), and cohort F (dMMR non-EC) of the GARNET trial.
Methods
This multicenter, open-label, single-arm study is being conducted in 2 parts: dose escalation and expansion. Patients with dMMR solid tumors, MMRp EC, and NSCLC that progressed on or after a platinum regimen received 500 mg of IV dostarlimab every 3 weeks (Q3W) for the first 4 cycles, then 1000 mg IV every 6 weeks (Q6W) for up to 2 years or until disease progression or discontinuation.
Results
A total of 515 patients were included. Of these patients, 60 (11.7%) experienced TRAEs leading to treatment interruption, and 25 (4.9%) experienced TRAEs leading to discontinuation. The most common TRAEs leading to treatment interruption were diarrhea (1.2%), pneumonitis (1.2%), and fatigue (1.0%), whereas the most common TRAEs leading to discontinuation were alanine aminotransferase increased (0.8%), aspartate aminotransferase increased (0.6%), and transaminase increased (0.6%). The most common TRAEs of any grade were fatigue (15.0%), diarrhea (12.8%), and asthenia (11.5%). Grade ≥3 TRAEs were uncommon (13.6%); the most common were anemia (1.7%), fatigue (1.6%), and lipase increased (1.4%). Most endocrine system TRAEs were grade ≤3; the most common were hypothyroidism (9.3%), hyperthyroidism (3.1%), and adrenal insufficiency (1.4%). The AE profile was consistent across all tumor types included. Rates of AEs did not increase when changing from 500-mg Q3W to 1000-mg Q6W dosing. No deaths were attributed to dostarlimab.
Conclusions
Safety with dostarlimab was consistent with the anti–PD-1 drug class. Most TRAEs were low grade, with few leading to interruption or discontinuation. No increase in the rate of TRAEs was seen after transitioning to the 1000-mg Q6W dosing schedule.
Clinical trial identification
NCT02715284.
Editorial acknowledgement
Writing and editorial support, funded by GlaxoSmithKline (Waltham, MA, USA) and coordinated by Heather Ostendorff-Bach, PhD, of GlaxoSmithKline, was provided by Shannon Morgan-Pelosi, PhD, and Jennifer Robertson, PhD, of Ashfield MedComms, an Ashfield Health company (Middletown, CT, USA).
Legal entity responsible for the study
GlaxoSmithKline.
Funding
GlaxoSmithKline.
Disclosure
T. André: Financial Interests, Personal, Advisory Role: BMS, MSD Oncology, Amgen, AstraZeneca, Vantana, Roche, Seagen, GlaxoSmithKline, Halliodx, Servier, Sanofi, and Pierre Fabre. A. Oaknin: Financial Interests, Personal, Advisory Role: GlaxoSmithKline, Immunogen, Genmab, Mersana Therapeutics, Roche, AstraZeneca, MSD, Sutro, and Deciphera Pharmaceuticals; Financial Interests, Institutional, Research Grant: institutional grants from Abbie Deutchland, Ability Pharmaceuticals, Advaxis Inc, AeternaZentaris, Amgen SA, Aprea Therapeutics AB, Clovis Oncology Inc, Eisai Ltd, F. Hoffmann - La Roche Ltd, Regeneron Pharmaceuticals, Immunogen Inc, Merck Sharp & Dohme; Non-Financial Interests, Personal, Other, Travel support: Roche, AstraZeneca, PharmaMar, and Clovis Oncology. V. Moreno Garcia: Financial Interests, Personal, Advisory Role: BMS, Bayer, Pieris, and Janssen. G. Curigliano: Financial Interests, Personal, Advisory Role: Roche, BMS, Pfizer, Seattle Genetics, and Ellipsis. J. Trigo: Financial Interests, Institutional, Research Grant: AstraZeneca and MSD; Financial Interests, Personal, Advisory Role: AstraZeneca, BMS, MSD, Takeda, and Boehringer Ingelheim. M. Barretina-Ginesta: Financial Interests, Personal, Advisory Role: GlaxoSmithKline, Clovis Oncology, PharmaMar, AstraZeneca, MSD, and Roche; Non-Financial Interests, Personal, Other, Travel support: GlaxoSmithKline, PharmaMar, AstraZeneca, MSD, and Roche. S. Ellard: Financial Interests, Personal, Stocks/Shares: GlaxoSmithKline. A.V. Tinker: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Role: from AstraZeneca and Eisai. R. Miller: Financial Interests, Personal, Advisory Role: Merck, GlaxoSmithKline, AZD, Ellipses, Shigoni, and Clovis Oncology; Financial Interests, Personal, Speaker’s Bureau: GlaxoSmithKline, AZD, and Clovis Oncology; Non-Financial Interests, Personal, Other, Travel support: GlaxoSmithKline and AZD; Financial Interests, Institutional, Funding: Merck. J. Pikiel: Financial Interests, Personal, Advisory Role, honoraria: Amgen, Clovis Oncology, Icyte, Novartis, Odonate Therapeutics, Pfizer, Regeneron, Roche, and GlaxoSmithKline; Non-Financial Interests, Personal, Other, Travel support: Roche. V. Boni: Financial Interests, Personal, Advisory Role: OncoArt and Guidepoint Global; Financial Interests, Personal, Speaker’s Bureau: Solti; Financial Interests, Personal, Advisory Role: START; Financial Interests, Personal, Leadership Role: Loxo and IDEAYA Biosciences; Financial Interests, Institutional, Research Grant: Sanofi, Seattle Genetics, Loxo, Novartis, CytomX Therapeutics, Pumo Biotechnology, Kura Oncology, GlaxoSmithKline, Roche/Genentech, BMS, Menarini, Synthon, Janssen Oncology, Merck, Lilly, Merus, Pfizer, Bayer, Incyte, Abbvie, Zenith Epigenetics, Genmab, A. B. Pothuri: Financial Interests, Institutional, Research Grant: GlaxoSmithKline, AstraZeneca, Merck, Genentech/Roche, Celsion, Mersana, and Clovis Oncology; Financial Interests, Personal, Advisory Board: GlaxoSmithKline, AstraZeneca, Merck, Eisai, Toray, Mersana, Elevar, Arquer, and Clovis Oncology. Y. Drew: Financial Interests, Personal, Advisory Board: GlaxoSmithKline, AstraZeneca, Clovis Oncology, Merck, Genmab; Financial Interests, Institutional, Research Grant: AstraZeneca, Clovis Oncology, and Verrastem; Non-Financial Interests, Personal, Other, Travel support: AstraZeneca, Clovis Oncology, and GlaxoSmithKline. J. Veneris: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. E. Im: Financial Interests, Personal, Full or part-time Employment, Employed by GlaxoSmithKline when the study was conducted.: GlaxoSmithKline. S. Banerjee: Financial Interests, Personal, Advisory Role: OncoArt and Guidepoint Global; Financial Interests, Personal, Speaker’s Bureau: Solti; Financial Interests, Personal, Advisory Role, Honoraria: Loxo and IDEAYA Biosciences; Financial Interests, Institutional, Research Grant: Sanofi, Seattle Genetics, Loxo, Novartis, CytomX Therapeutics, Pumo Biotechnology, Kura Oncology, GlaxoSmithKline, Roche/Genentech, BMS, Menarini, Synthon, Janssen Oncology, Merck, Lilly, Merus, Pfizer, Bayer, Incyte, Abbvie, Zenith Epigenetics, Genmab. All other authors have declared no conflicts of interest.