Abstract 76P
Background
Dostarlimab is a humanized programmed death 1 (PD-1) receptor monoclonal antibody that blocks interaction with the PD-1 ligands, PD-L1 and PD-L2. GARNET is a phase 1 study assessing antitumor activity and safety of dostarlimab monotherapy in pts with solid tumors. Here we report on association of antitumor activity and TMB in 2 EC cohorts.
Methods
This multicenter, open-label, single-arm study is being conducted in 2 parts: dose escalation and expansion. Two expansion cohorts enrolled pts with advanced/recurrent EC determined by mismatch repair (MMR) deficiency status: deficient MMR (dMMR; cohort A1), and MMR proficient (MMRp; cohort A2). MMR status was determined by immunohistochemistry. Pts received 500 mg of dostarlimab IV Q3W for 4 cycles, then 1000 mg IV Q6W until disease progression/discontinuation. Primary endpoints were objective response rate (ORR) and duration of response by RECIST v1.1 per blinded independent central review. TMB status was an exploratory biomarker determined using the FoundationOne test. TMB-H was defined as ≥10 mutations/megabase; TMB-L was defined as <10 mutations/megabase.
Results
The efficacy population included 245 pts, 103 (85 TMB-H) in A1 and 142 (9 TMB-H) in A2. ORRs were 44.7% (A1) and 13.4% (A2). In TMB-H pts, the ORRs were 44.7% (A1) and 44.4% (A2). Full ORR results by TMB status are shown in the table. Safety was previously reported.1
Conclusions
TMB-H status was more frequent in the dMMR pts, which is in line with known characteristics of these biomarkers. TMB-H status correlated with a higher ORR in both cohorts. Note that the study was not powered to assess antitumor activity by TMB status, and interpretation is limited by the small number of pts in each subgroup. Additional mutational analysis is ongoing. Table: 76P
| n[JR1] /Na (% [95%CI]) | Cohort A1 (dMMR) | Cohort A2 (MMRp) | Overall |
| TMB-H | 38/85 (44.7 [33.9–55.9]) | 4/9 (44.4 [13.7–78.8]) | 42/94 (44.7 [34.4–55.3]) |
| TMB-L | 3/13 (23.1 [5.0 – 53.8]) | 15/128 (11.7 [6.7–18.6]) | 18/141 (12.8 [7.7–19.4]) |
| Not available | 5/5 (100 [47.8–100]) | 0/5 (0) | 5/10 (50.0 [18.7–81.3]) |
| Overall | 46/103 (44.7 [34.9–54.8]) | 19/142 (13.4 [8.3–20.1]) | 65/245 (26.5 [21.1–32.5]) |
aN (denominator) represents number of pts in group; n (numerator) represents number of pts in group with a response. 1Oaknin A, et al. Int J Gynecol Cancer 2020;30(suppl4): A39–A40.
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 Nicole Renner, 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
A. Oaknin: Financial Interests, Personal, Advisory Role: GlaxoSmithKline, Immunogen, Genmab, Mersana Therapeutics, Deciphera Pharmaceuticals; Financial Interests, Institutional, Research Grant: Abbie Deutchland, Ability Pharmaceuticals, Advaxis Inc, Aeterna Zentaris, Amgen SA, Aprea Therapeutics AB, Clovis Oncology Inc, Eisai Ltd, F. Hoffmann - La Roche Ltd, Regeneron Pharmaceuticals, Immunogen Inc, Merck Sharp & Dohme de Espana SA, Millennium P; Non-Financial Interests, Personal, Other, Travel support: Roche, AstraZeneca, PharmaMar, Clovis Oncology. L. Gilbert: Financial Interests, Personal, Advisory Role: Merck, AstraZeneca, Pfizer. A. Tinker: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Role: AstraZeneca, Eisai. J. Brown: Financial Interests, Personal, Other, Honoraria: Olympus; Financial Interests, Personal, Advisory Role: Caris, GlaxoSmithKline, Clovis, AstraZeneca, Genentech; Financial Interests, Institutional, Speaker’s Bureau: Clovis. C. Mathews: Financial Interests, Institutional, Research Grant: GlaxoSmithKline. J.Z. Press: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca. R. Sabatier: Financial Interests, Institutional, Research Grant: Eisai, AstraZeneca; Financial Interests, Personal, Advisory Role: Roche, Pfizer, GlaxoSmithKline, Novartis, AstraZeneca; Non-Financial Interests, Personal, Advisory Role: Roche, Pfizer, AstraZeneca, Amgen. D. O'Malley: Financial Interests, Personal, Advisory Role: Immunogen, Eisai, Agenus, GlaxoSmithKline; Financial Interests, Personal, Advisory Board: Clovis, Ambry, AbbVie, Janssen/J&J, Regeneron, Novacure, Myriad Genetics, Tarveda, Amgen, VentiRx, Array Biopharma, EMD Serono, Ergomed; Financial Interests, Institutional, Sponsor/Funding: Ajinomoto Inc, Ludwig Cancer Research, Stemcentrx Inc, Cerulean Pharma, GOG Foundation, Bristol Myers Squibb, Serono Inc, Tracon Pharmaceuticals, Yale University, New Mexico Cancer Care Alliance, INC Research Inc, Inventiv Health Clinical, Iovance Biother; Financial Interests, Personal, Other, Steering Committee: Genentech/Roche, Merck. V. Boni: Financial Interests, Personal, Advisory Role: OncoArt, Guidepoint Global; Financial Interests, Personal, Speaker’s Bureau: Solti; Non-Financial Interests, Personal, Other, Travel support: START; Financial Interests, Personal, Advisory Role, Honoraria: Loxo, Ideaya Biosciences; Financial Interests, Institutional, Research Grant: Sanofi, Seattle Genetics, Loxo, Novartis, CytomX Therapeutics, Pumo Biotechnology, Kura Oncology, GlaxoSmithKline, Roche/Genentech, Bristol Myers Squibb, Menarini, Synthon, Janssen Oncology, Merck, Lilly, Merus, Pfizer, Bayer, Incyte, AbbVie, Zenith Epige. L. Duska: Financial Interests, Personal, Advisory Role: AstraZeneca, Genentech/Roche, MorphoTek, Merck, Innovio, Advance Medical, UpToDate, Cue Biopharma, British Journal of OB/GYN, Parexel, State of California, Elsevier, ASCO, ClearView Health Care, National Cancer Institute, JB Learning; Financial Interests, Institutional, Research Grant: Cerulean/NextGen, AbbVie, GlaxoSmithKline, Pfizer, Novartis, Morab, Morphotek, Merck, Aduro BioTech, Syndax, Ludwig, LEAP Therapeutics, Eisai, Lycera, Genentech/Roche, Inovio, Advaxis. S. Ghamande: Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Institutional, Speaker’s Bureau: GlaxoSmithKline; Financial Interests, Institutional, Funding: GlaxoSmithKline, Merck, Roche, Genentech, Takeda, Seattle Genetics, Advaxis, BMS, Clovis, AbbVie. P. Ghatage: Financial Interests, Personal, Advisory Role: AstraZeneca, GSK, Eisai; Financial Interests, Institutional, Research Grant: AstraZeneca. R. Kristeleit: Financial Interests, Personal, Advisory Role: GlaxoSmithKline. C. Leath III: Financial Interests, Personal, Research Grant: GlaxoSmithKline; Financial Interests, Institutional, Advisory Board: GlaxoSmithKline, Eisai, Clovis Oncology, Seattle Genetics, AbbVie. X. Han: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. S. Kumar: Financial Interests, Personal, Full or part-time Employment, Former employee of GlaxoSmithKline: GlaxoSmithKline. T. Duan: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. E. Im: Financial Interests, Personal, Full or part-time Employment, Former employee of GlaxoSmithKline: GlaxoSmithKline. B. Pothuri: Financial Interests, Institutional, Sponsor/Funding,Iindustry-sponsored trials: Tesaro/GSK, AstraZeneca, Merck, Genentech/Roche, Celsion, Clovis Oncology; Financial Interests, Institutional, Advisory Board: Tesaro/GSK, AstraZeneca, Merck, Toray, Mersana, Elevar, Eisai. All other authors have declared no conflicts of interest.