Abstract LBA36
Background
Dostarlimab (TSR-042) is a humanized programmed death (PD)-1 receptor monoclonal antibody that blocks interaction with the PD-1 ligands. GARNET is a phase I study assessing antitumor activity and safety of dostarlimab monotherapy in pts with solid tumors.
Methods
This multicenter, open-label, single-arm study includes dose escalation and expansion parts. Here we report on 2 independent expansion cohorts of pts with recurrent or advanced EC (dMMR EC and MMRp EC, determined by immunohistochemistry [IHC]) that progressed on or after a platinum-based chemotherapy regimen. Pts received 500 mg dostarlimab IV Q3W for 4 cycles, then 1000 mg Q6W until disease progression, discontinuation, or withdrawal. The primary endpoints are objective response rate (ORR) and duration of response (DOR) by blinded independent central review using RECIST v1.1.
Results
In total, 126 dMMR and 145 MMRp pts identified by IHC were enrolled and dosed. Of these, 103 and 142 pts had sufficient follow-up time (24 wks) for efficacy analyses, respectively. dMMR ORR was 44.7%; MMRp ORR was 13.4% (Table). Median DOR and OS were not reached. The most common grade ≥3 TEAEs (N=271) were anemia (12.2%), abdominal pain (4.8%), and dyspnea (4.1%). The most common grade ≥3 immune-related TEAEs were diarrhea, aspartate aminotransferase increased, and alanine aminotransferase increased (1.8% each). There were no treatment-related deaths.
Conclusions
Dostarlimab demonstrated durable antitumor activity in both dMMR and MMRp advanced/recurrent EC. dMMR status by IHC was associated with a higher response rate. No new safety signals were detected. These cohorts are the largest prospective evaluation of a PD-(L)1 therapy in EC to date. Table: LBA36
| Variable, unit | dMMR N=103 | MMRp N=142 |
| Median follow-up, mo | 16.3 | 11.5 |
| ORR, n (% [95% CI]) Complete response, n (%) Partial response, n (%) Stable disease, n (%) | 46 (44.7 [34.9–54.8]) 11 (10.7) 35 (34.0) 13 (12.6) | 19 (13.4 [8.3–20.1]) 3 (2.1) 16 (11.3) 31 (21.8) |
| Disease control rate, n (% [95% CI]) | 59 (57.3 [47.2–67.0]) | 50 (35.2 [27.4–43.7]) |
| Response ongoing, n (%) | 41 (89.1) | 12 (63.2) |
| 18 mo DOR, % (95% CI) | 79.2 (54.9–91.3) | 61.3 (32.5–80.8) |
Clinical trial identification
NCT02715284.
Editorial acknowledgement
Writing and editorial support, funded by GlaxoSmithKline (Waltham, MA, USA) and coordinated by Heather Ostendorff-Back, PhD of GlaxoSmithKline was provided by Nicole Renner, PhD and Anne Cooper of Ashfield Healthcare Communications (Middletown, CT, USA).
Legal entity responsible for the study
GlaxoSmithKline, Waltham, MA, USA.
Funding
GlaxoSmithKline, Waltham, MA, USA.
Disclosure
A. Oaknin: Honoraria (institution), Advisory/Consultancy: AstraZeneca; Honoraria (institution), Advisory/Consultancy: Tesaro; Honoraria (institution), Advisory/Consultancy: Clovis; Honoraria (institution), Advisory/Consultancy: PharmaMar; Honoraria (institution), Advisory/Consultancy: Roche. L. Gilbert: Advisory/Consultancy: Merck; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Pfizer. A.V. Tinker: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca. R. Sabatier: Research grant/Funding (institution): Eisai; Advisory/Consultancy, Non-remunerated activity/ies: Roche; Advisory/Consultancy, Non-remunerated activity/ies: Pfizer; Advisory/Consultancy: Tesaro; Advisory/Consultancy: Novartis; Advisory/Consultancy, Non-remunerated activity/ies: AstraZeneca; Non-remunerated activity/ies: Amgen. D.M. O'Malley: Advisory/Consultancy: Tesaro, Immunogen, Eisai, Agenus, GSK; Advisory/Consultancy: Clovis, Ambry, AbbVie; Advisory/Consultancy: Janssen/J&J, Regeneron, Novacure, Myraid Genetics, Tarveda; Advisory/Consultancy: Amgen; Advisory/Consultancy: Genentech/Roche, Merck; Research grant/Funding (institution): VentiRx, Array Biopharma, EMD Serono, Ergomed; Research grant/Funding (institution): Ajinomoto Inc, Ludwig Cancer Research; Research grant/Funding (institution): Stemcentrx, Inc, Cerulean Pharma, GOG Foundation; Research grant/Funding (institution): BMS, Serono Inc, Tracon Pharmaceuticals; Research grant/Funding (institution): Yale University, New Mexico Cancer Care Alliance; Research grant/Funding (institution): INC Research, Inc., Inventiv Health Clinical; Research grant/Funding (institution): Iovance Biotherapeutics, Inc, PRA Intl. S. Ghamande: Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Tesaro; Speaker Bureau/Expert testimony, Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Advaxis; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Clovis; Research grant/Funding (institution): AbbVie. L. Duska: Research grant/Funding (institution): Merck, Genentech/Roche, GlaxoSmithKline, Inovio; Advisory/Consultancy: AstraZeneca, Genentech/Roche, MorphoTek; Advisory/Consultancy: Merck, Cue Biopharma; Licensing/Royalties: Elsevier, JB Learning. W. Guo: Full/Part-time employment: GlaxoSmithKline. E. Im: Full/Part-time employment: GlaxoSmithKline. B. Pothuri: Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies: Tesaro; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Clovis Oncology. All other authors have declared no conflicts of interest.