Department of Oncology & Radiotherapy and Early Phase Clinical Trials Centre, Medical University of Gdańsk, Gdańsk, Poland
Rafal Dziadziuszko , Fabrice Barlesi , Jeong Eun Kim , Shirish M. Gadgeel , Maciej Krzakowski , Jae Ho Jeong , Gennaro Daniele , David Chen , Youyou Hu , Timothy R. Wilson , Brian P. Simmons , David Morgan Thomas
Background: Studies have suggested that pts with TMB-high tumors could derive clinical benefit from atezolizumab, a PD-L1 inhibitor; however, these studies used inconsistent TMB cutoffs. We report efficacy and safety data of atezolizumab in adult and pediatric pts with TMB-high advanced/metastatic solid tumors from Cohort D of the TAPISTRY trial (NCT04589845), using two TMB cutoffs: ≥13 mutations [mut]/Mb and ≥16 mut/Mb. Methods: TAPISTRY is a phase II, global, open-label, multicohort basket trial evaluating the efficacy and safety of multiple therapies in pretreated pts with advanced/metastatic solid tumors. Pts in Cohort D had advanced unresectable/metastatic, PD-L1 inhibitor-naïve, TMB-high (≥13 mut/Mb) solid tumors. Atezolizumab was given every 21 days, at 1200 mg in pts ≥18 years old, and at ≥15 mg/kg (up to 1200 mg) in pts <18 years old. Tumor responses were assessed per RECIST v1.1. Primary endpoint: objective response rate (ORR) by independent review committee (IRC) in pts with TMB ≥16 mut/Mb. Secondary endpoints included ORR by IRC in pts with TMB ≥13 mut/Mb, duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. Results: At data cut-off (Nov 9, 2023), 150 pts with TMB ≥13 mut/Mb were enrolled. In the safety-evaluable population (n = 148), median age was 63 years (range 11–86); 56% of pts were male, and 56% had received ≥2 prior lines of therapy (median 2; range 0–14). The efficacy-evaluable population included 129 pts with TMB ≥13 mut/Mb (TMB ≥16 mut/Mb; n = 111); the most common tumor types were colorectal (n = 40; 31%), breast, and gastroesophageal cancer (n = 11 each; 9%). Key outcomes are presented (Table). After a median follow-up of 9.8 months, ORR by IRC was comparable between pts with TMB ≥16 mut/Mb (22.5%) and pts with TMB ≥13 mut/Mb (20.2%). Responses were seen across a variety of tumor types. DoR 6- and 12-month event-free rates were 79% and 72%, respectively. Median PFS was short, suggesting fast disease progression in non-responders. Fatigue (22%) and anemia (20%) were the most common adverse events. Safety of atezolizumab was consistent with its known profile. Conclusions: Atezolizumab was well tolerated and led to antitumor activity in pts with TMB-high solid tumors. Responses were seen across a variety of tumor types. Clinical trial information: NCT04589845.
Efficacy | TMB ≥16 mut/Mb (n = 111) | TMB ≥13 mut/Mb (n = 129) |
---|---|---|
Objective response rate, n (%) [95% CI] | 25 (22.5) [15.1–31.4] | 26 (20.2) [13.6–28.1] |
Complete / partial response | 4 (3.6) / 21 (18.9) | 4 (3.1) / 22 (17.1) |
Stable disease / progressive disease / missing | 37 (33.3) / 39 (35.1) / 10 (9.0) | 43 (33.3) / 49 (38.0) / 11 (8.5) |
Median DoR, months (95% CI) | NE (20.8–NE) | NE (20.8–NE) |
Median PFS, months (95% CI) | 2.8 (1.7–5.4) | 2.7 (1.5–4.2) |
Median OS, months (95% CI) | 15.0 (9.1–21.5) | 16.1 (9.1–21.4) |
Safety, n (%) | Safety-evaluable; n = 148 | |
≥1 AE / Grade 3–5 AEs / serious AE | 138 (93.2) / 60 (40.5) / 41 (27.7) | |
≥1 TRAE | 79 (53.4) |
(TR)AE, (treatment-related) adverse event.
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