Efficacy and safety of dostarlimab in patients (pts) with mismatch repair deficient (dMMR) solid tumors: Analysis of 2 cohorts in the GARNET study.
Bibliographic record
Abstract
2587 Background: Dostarlimab is a programmed death 1 (PD-1) inhibitor approved in the US as a monotherapy in pts with dMMR solid tumors that have progressed on or after prior treatment, with no satisfactory alternative treatment options; or dMMR advanced/recurrent (AR) endometrial cancer (EC) that has progressed on or after treatment with a platinum-based chemo; and in the EU as a monotherapy in pts with dMMR/ microsatellite instabilityhigh (MSI-H) AR EC that has progressed on or after treatment with a platinum-based chemo. Here we report on efficacy and safety in 2 expansion cohorts that enrolled pts with dMMR solid tumors. Methods: GARNET is a multicenter, open-label, single-arm phase 1 study. Cohort A1 enrolled pts with dMMR/MSI-H AR EC; cohort F enrolled pts with dMMR/MSI-H/POLε-mut non-EC solid tumors. Pts received 500 mg of IV dostarlimab Q3W for 4 cycles, then 1000 mg Q6W until PD, discontinuation, or withdrawal. Primary endpoints were ORR and DOR by BICR per RECIST v1.1. Biomarker status was based on local assessment. Results: For this third interim analysis, 153 pts with dMMR/MSI-H EC and 210 pts with dMMR/MSI-H/POLε-mut non-EC solid tumors (56% colorectal cancer, 11% gastric) were enrolled and treated. Efficacy analysis was performed for 143 dMMR/MSI-H EC and 204 dMMR/MSI-H/POLε-mut non-EC pts who had measurable disease at baseline and ≥6 mo of follow-up. ORRs were 45.5% (dMMR/MSI-H EC) and 43.1% (dMMR/POLε-mut non-EC solid tumors; Table). Probability of PFS at 6, 9, and 12 mo was 49.5%, 48.0%, and 46.4% in dMMR/MSI-H EC and 51.8%, 48.1%, and 46.4% in dMMR/MSI-H/POLε-mut non-EC. Median (m) DOR and mOS were not reached for either cohort. A total of 13 pts (8.5%) with dMMR/MSI-H EC and 12 pts (5.7%) with dMMR/MSI-H/POLε-mut non-EC solid tumors discontinued owing to a treatment-related adverse event (TRAE). TRAEs occurring in ≥12% of pts were diarrhea, asthenia, fatigue, nausea, and pruritis (dMMR/MSI-H EC) and diarrhea, asthenia, and pruritus (dMMR/MSI-H/POLε-mut non-EC solid tumors). 2 deaths (1 hepatic ischemia, 1 suicide) were attributed by investigators to dostarlimab in pts with non-EC solid tumors. Conclusions: Dostarlimab demonstrated durable antitumor activity across 16 tumor types in pts with dMMR solid tumors, confirming efficacy in a larger sample size with extended follow-up. The safety profile was acceptable, with manageable toxicities. Clinical trial information: NCT02715284. [Table: see text]
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".