1 This change is reflected by biomarker-linked approvals, including the recent US Food and Drug Administration tissue-agnostic drug approvals for tumors characterized by defective mismatch repair (MMR) machinery. However, advancements in precision medicine have led to the development of biomarker-driven tumor-agnostic treatments. Trial Registration Identifier: NCT02715284Ĭlassification and treatment of cancers have historically been based on tumor type and histological subtype. These findings suggest that dostarlimab provides meaningful long-term benefit in a population with high unmet need. No new safety concerns were identified.Ĭonclusions And Relevance In this nonrandomized controlled trial, dostarlimab was a well-tolerated treatment option with rapid, robust, and durable antitumor activity in patients with diverse dMMR solid tumors. The most frequent immune-related adverse events were hypothyroidism (25 ), alanine aminotransferase increase (21 ), and arthralgia (17 ). Median overall survival was not reached (95% CI, 31.6 months to not reached). Median progression-free survival was 6.9 months (95% CI, 4.2 to 13.6 months) probability of progression-free survival at 24 months was 40.6% (95% CI, 35.0% to 46.1%). Median duration of response was not reached (range, ≥1.18 to ≥47.21 months) 72.2% of responders (104 of 144) had a response lasting 12 or more months. Objective response rate assessed per blinded independent central review for dMMR solid tumors was 44.0% (95% CI, 38.6% to 49.6%). All patients had at least 1 previous line of therapy. Results The efficacy population included 327 patients (median age, 63 years 235 female 7 Asian, 6 Black, and 206 White patients), with 141 patients (43.1%) with dMMR endometrial cancer, 105 patients (32.1%) with dMMR colorectal cancer, and 81 patients (24.8%) with other dMMR tumor types. Main Outcomes and Measures The primary objective was to evaluate objective response rate and duration of response in patients with dMMR solid tumors by blinded independent central review using Response Evaluation Criteria in Solid Tumors, version 1.1. Interventions Patients received 500 mg of dostarlimab intravenously every 3 weeks for 4 doses, then 1000 mg every 6 weeks until disease progression, discontinuation, or withdrawal. The data cut for this interim analysis was from November 1, 2021, with median follow-up of 27.7 months. Participants had advanced or recurrent dMMR and microsatellite instability–high (MSI-H) or polymerase epsilon (POLE)–altered solid tumors. Objective To assess the antitumor activity and safety of dostarlimab in patients with advanced or recurrent dMMR solid tumors.ĭesign, Setting, And Participants The GARNET trial was a phase 1, open-label, single-group, multicenter study that began enrolling May 8, 2017. Importance Mismatch repair deficiency (dMMR) occurs in various cancers, and these tumors are attractive candidates for anti–programmed cell death 1 therapies, such as dostarlimab, a recently approved immune checkpoint inhibitor. Shared Decision Making and Communication.Scientific Discovery and the Future of Medicine.Health Care Economics, Insurance, Payment.Clinical Implications of Basic Neuroscience.Challenges in Clinical Electrocardiography.Antitumor Activity Results by TMB and PD-L1 Status for dMMR EC and Non-EC Solid Tumors ORR by TMB as Continuous VariableĮTable 7. ORR by CPS as Continuous VariableĮFigure 9. CPS and TMB Distribution by CohortĮFigure 8. Prevalence of TMB and PD-L1 in GARNET Cohorts A1 and FĮFigure 7. Exploratory Analysis of BiomarkersĮFigure 6. Duration of Treatment for Patients With POLE-Altered Solid TumorsĮAppendix 3. POLE-Altered Antitumor Activity Analysis by BICRĮFigure 5. Demographics and Baseline Characteristics of Patients With POLE AlterationsĮTable 6. Enrollment and Outcomes for Patients With POLE-Altered TumorsĮTable 5. Progression-Free Survival by Best Overall Response per BICR in the Overall Efficacy PopulationĮFigure 4. Overall Survival by Tumor TypeĮAppendix 2. Progression-Free Survival by Tumor TypeĮFigure 3. Duration of Treatment for Responders With dMMR Solid TumorsĮFigure 2. Sites and Investigators and Supplementary MethodsĮFigure 1.
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