Abstract 547P
Background
Biomarkers are used to classify EC into molecular subtypes such as TCGA and/or a surrogate classification (POLε mutated [mut], mismatch repair/microsatellite instability [MMR/MSI], TP53mut, and no specific mutation profile [NSMP]) or by estrogen receptor (ER) status. Here, we report on a post hoc analysis of objective response rate (ORR) by a surrogate classification for EC in patients (pts) receiving dostarlimab monotherapy.
Methods
GARNET is a multicenter, open-label, single-arm phase 1 study. Pts were assigned to cohort A1 (MMR deficient/MSI–high [dMMR/MSI-H EC]) or A2 (MMR proficient/microsatellite stable [MMRp/MSS] EC) based on local assessment. Pts received 500 mg of dostarlimab IV Q3W for 4 cycles, then 1000 mg Q6W until disease progression, discontinuation, or withdrawal. The primary endpoints were ORR and duration of response by blinded independent central review. Molecular subtype was determined by POLε and TP53 mutation status by Foundation Medicine, and MMR/MSI status was determined by local immunohistochemistry (IHC) or next-generation sequencing; all others were assigned as NSMP. The hierarchy for classification was POLεmut → MMR/MSI → TP53 status → NSMP. ER status was determined by local IHC testing. Only pts with samples available for additional biomarker testing were included in the biomarker assessment.
Results
143 dMMR/MSI-H and 156 MMRp/MSS pts were included in the efficacy evaluable population. ORR was determined for molecular subtypes and ER expression (table). Safety has been previously reported. Table: 547P
| A1 | A2 | |||||
| Overall | 65/143, 45.5% (37.1–54.0) | 24/156, 15.4% (10.1–22.0) | ||||
| Molecular subtype | N=101 | N=153 | ||||
| Polεmut | 2/3, 66.7% (9.4–99.2) | 0/2, 0% (0.0–84.2) | ||||
| dMMR/MSI-H | 43/98, 43.9% (33.9–54.3) | |||||
| TP53mut10/26,38.5% (20.2–59.4) | TP53wt33/72,45.8% (34.0–58.0) | |||||
| ERpos19/44,43.2% (28.3–59.0) | ERneg1/2,50.0% (1.3–98.7) | ERunk23/52, 44.2% (28.3–59.0) | ||||
| TP53mut | 17/94, 18.1% (10.9–27.4) | |||||
| ERpos4/28, 14.3% (4.0–32.7) | ERneg7/19,36.8% (16.3–61.6) | ERunk6/47,12.8% (4.8–25.7) | ||||
| NSMP | 7/57 12.3% (5.1–23.7) | |||||
| ERpos2/19,10.5% (1.3–33.1) | ERneg2/11,18.2% (2.3–51.8) | ERunk3/27,11.1% (2.4–29.2) | ||||
Data are n/N, % (95% CI). Datacut: 1 Nov 2021. ERneg, ER negative; ERpos, ER positive; ERunk, ER unknown; wt, wild-type.
Conclusions
The observed ORRs in each molecular subgroup were consistent with the overall ORR in each cohort. Differences by ER expression status were not observed. These findings support the importance of testing pts with EC for MMR/MSI biomarker status as a predictor of response. Additionally, data suggest that TP53 mutation or ER expression should not modify treatment approach. The data are of interest for hypothesis generation.
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, Waltham, MA, USA.
Funding
GlaxoSmithKline.
Disclosure
A. Oaknin: Financial Interests, Personal, Other, Consulting Fees: AstraZeneca, Bristol Myers Squibb, Deciphera Pharmaceutical, Genmab, GlaxoSmithKline, ImmunoGen, Mersana Therapeutics, Roche, and Sutro; Financial Interests, Personal, Other, Institutional Grants: Abbie Deutchland, Ability Pharmaceuticals, Advaxis Inc, Aeterna Zentaris, Amgen SA, Aprea Therapeutics AB, Clovis Oncology Inc, Eisai Ltd, F. Hoffmann–La Roche Ltd, GlaxoSmithKline, ImmunoGen Inc, Merck Sharp & Dohme de Espana SA, Millennium Pharmaceutica; Financial Interests, Personal, Other, Travel Support: AstraZeneca, Clovis Oncology, PharmaMar, and Roche. B. Pothuri: Financial Interests, Personal, Other, Institutional Grants: AstraZeneca, Celsion, Clovis Oncology, Eisai, Genentech/Roche, Karyopharm, Merck, Mersana, Takeda Pharmaceuticals, and Tesaro/GlaxoSmithKline; Financial Interests, Personal, Other, Consulting Fees: Arquer Diagnostics, AstraZeneca, Atossa, Clovis Oncology, Deciphera, Elevar Therapeutics, Imab, Mersana, Tesaro/GlaxoSmithKline, Merck, Sutro Biopharma, and Tora; Financial Interests, Personal, Other, Meeting Support: GOG Partners; Financial Interests, Personal, Advisory Board: Arquer Diagnostics, AstraZeneca, Atossa, Clovis Oncology, Deciphera, Eisai, Elevar Therapeutics, Imab, Merck, Mersana, Sutro Biopharma, Tesaro/GlaxoSmithKline, and Toray; Financial Interests, Personal, Leadership Role: GOG Partners. L. Gilbert: Financial Interests, Personal and Institutional, Research Grant: Alkermes, AstraZeneca, Clovis, Esperas, ImmunoGen Inc, IMV, Karyopharm, Merck Sharp & Dohme, Mersana, Novocure GmbH, OncoQuest Pharmaceuticals, Pfizer, Roche, and Tesaro; Financial Interests, Personal, Other, Consulting Fees: Merck; Financial Interests, Personal, Other, Honoraria: Alkermes, AstraZeneca, Eisai, Eisai-Merck, and GlaxoSmithKline. R. Sabatier: Financial Interests, Personal and Institutional, Research Grant: AstraZeneca and Eisai; Financial Interests, Personal, Other, Personal Fees: AstraZeneca, GlaxoSmithKline, Novartis, Pfizer, and Roche; Financial Interests, Personal, Other, Non-Financial Support: AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Pfizer, and Roche. J. Brown: Financial Interests, Personal, Advisory Role: Caris, Clovis, Eisai, and GlaxoSmithKline; Financial Interests, Personal, Research Grant: Genentech and GlaxoSmithKline. S. Ghamande: Financial Interests, Institutional, Other, Institutional Fees: Georgia Cancer Center ; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Speaker’s Bureau: GlaxoSmithKline; Financial Interests, Personal and Institutional, Funding: Abbvie, Advaxis, Bristol Myers Squibb, Clovis, Genentech, GlaxoSmithKline, Merck, Roche, Seattle Genetics, and Takeda. C. Mathews: Financial Interests, Personal and Institutional, Research Grant: Astellas, AstraZeneca, Deciphera, GlaxoSmithKline, Moderna, Regeneron, and Seattle Genetics; Financial Interests, Personal, Advisory Board: IMAB Biopharma. D. O'Malley: Financial Interests, Personal, Other, Personal Fees: Abbvie, Agenus, Ambry, Amgen, Arquer Diagnostics, AstraZeneca, Celsion Corp, Clovis, Corcept Therapeutics, Eisai, Elevar, Genentech/Roche, GOGFoundation, Immunogen, Inxmed, Iovance, Janssen/J&J, Merck, Mersana, Myriad Genetics, Novartis, Novocure, Regene; Financial Interests, Personal, Other, Research Funding: Abbvie, Agenus, Ajinomoto Inc, Amgen, Array Biopharma, AstraZeneca, Bristol-Myers Squibb Co, Cerulean Pharma, Clovis, Eisai, EMD Serono, Ergomed, Genentech/Roche, GenMab, GOGFoundation, Immunogen, INC Research, inVentiv Health Clinical, Iovance, Janssen/. V. Boni: Financial Interests, Personal, Advisory Role: Guidepoint Global and OncoArt; Financial Interests, Personal, Speaker’s Bureau: Solti; Financial Interests, Personal, Other, Travel Support: START; Financial Interests, Personal, Other, Honoraria: IDEAYA Biosciences and Loxo; Financial Interests, Personal and Institutional, Funding, Institutional Grants: Abbvie, Adaptimmune, Alkermes, Amgen, Array BioPharma, AstraZeneca, Bayer, BioNTech AG, Boehringer Ingelheim, Boston Biomedical, Bristol-Myers Squibb, CytomX Therapeutics, Genmab, GlaxoSmithKline, Incyte, Janssen Oncology, Kura Oncology, Lilly, Loxo, Mena. A. Gravina: Financial Interests, Personal, Other, Personal Fees: Gentili ; Financial Interests, Personal, Other, Travel Support: Pfizer. S. Banerjee: Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, Clovis Oncology, GlaxoSmithKline, Immunogen, MSD, Mersana, Pfizer, Roche, and Takeda; Financial Interests, Personal, Other, Consulting Fees: Amgen, AstraZeneca, GenMab, GlaxoSmithKline, Immunogen, Merck Serono, Mersana, MSD, OncXerna, Seagen, and Shattuck Labs; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca and GlaxoSmithKline. R. Miller: Financial Interests, Personal, Other, Consulting Fees: AZD, Clovis Oncology, Ellipses, GlaxoSmithKline, MSD, and Shionogi; Financial Interests, Personal, Speaker’s Bureau: AZD, Clovis Oncology, GlaxoSmithKline, and Roche; Financial Interests, Personal, Other, Travel Grants: AZD and GlaxoSmithKline; Financial Interests, Personal, Other, Travel Funding: MSD. M.R. Mirza: Financial Interests, Personal, Advisory Role: AstraZeneca, Biocad, GlaxoSmithKline, Karyopharm, Merck, Roche, and Zailab; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca and GlaxoSmithKline; Financial Interests, Personal, Research Grant: Apexigen, AstraZeneca, Deciphera (trial chair), GlaxoSmithKline, and Ultimovacs; Financial Interests, Personal, Member of the Board of Directors: Karyopharm. T. Duan: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. X. Han: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. S. Zildjian: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. N. Dewal: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. J. Veneris: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. A.V. Tinker: Financial Interests, Personal, Other, Institutional Grants: AstraZeneca; Financial Interests, Personal, Other, Personal Fees: AstraZeneca and Eisai. All other authors have declared no conflicts of interest.