Abstract CT265: Trastuzumab emtansine in patients (pts) with HER2 mutation-positive (HER2mut) tumors: TAPISTRY study

Abstract Background: HER2 point mutations are found in ~1.4% of solid tumors, but prevalence varies across tumor types. Trastuzumab emtansine is an antibody-drug conjugate approved in HER2-overexpressing metastatic breast cancer. Here we present efficacy and safety data of trastuzumab emtansine in pts with HER2mut advanced/metastatic solid tumors (excluding HER2 amplifications) from Cohort F of the TAPISTRY trial (NCT04589845). Methods: TAPISTRY is a phase II, global, open-label, multi-cohort basket trial evaluating the efficacy and safety of multiple therapies in pts with advanced/metastatic solid tumors. Pts in Cohort F were ≥12 years old, with tumors harboring an activating HER2 mutation identified by NGS, and measurable disease by RECIST v1.1. Trastuzumab emtansine 3.6 mg/kg IV was administered every 21 days; tumor assessments were performed at screening, every 6 weeks from day 1/cycle 1 for one year, and every 9 weeks thereafter. Primary endpoint: objective response rate (ORR) by independent review committee (IRC). Key secondary endpoints: ORR by investigator; duration of response; progression-free survival; overall survival; safety. Results: At data cut-off (16 Jul 2023), 35 pts with 10 different tumor types were efficacy evaluable; the most common tumor type was non-small cell lung cancer (NSCLC; 31%). Baseline characteristics and key outcomes are presented in the Table. After a median follow-up of 7 months, ORR by IRC in efficacy-evaluable pts was 14.3% (n/N=5/35; 95% CI 4.8-30.3]). Responses were observed in 3 tumor types: NSCLC (n/N=1/11), breast (n/N=3/5), endometrial (n/N=1/1). The most frequent adverse events were decreased appetite, fatigue, and nausea (25.7% each). No new safety signals were identified. Conclusions: Trastuzumab emtansine in pts with HER2mut tumors (excluding HER2 amplifications) did not meet its primary endpoint. Trastuzumab emtansine was generally well tolerated and the safety profile was consistent with the known profile of the drug. TABLE 1. NAND Baseline characteristics Trastuzumab emtansine N=35 Median age, years (range) 67 (29-83) Female, n (%) 22 (62.9) Prior lines of therapy, n (%) - No prior lines of therapy/1 prior line of therapy/≥2 prior lines of therapy 1 (2.9)/8 (22.9)/26 (74.3) Efficacy N=35 Objective response rate by IRC, n (%) [95% CI] 5 (14.3)* [4.8-30.3] Complete response 0 Partial response 5 (14.3) Stable disease 14 (40.0) Progressive disease 10 (28.6) Missing† 6 (17.1) Clinical benefit rate by IRC, n (%)‡ 8 (22.9) Objective response rate by investigator, n (%) 2 (5.7) Median duration of response, months (95% CI) - By IRC/By investigator 9.4 (2.8-NE)/11.8 (8.3-NE) Median progression-free survival, months (95% CI) - By IRC/By investigator 3.3 (1.4-4.3)/2.7 (1.5-3.9) Median overall survival, months (95% CI) 10.0 (6.2-13.4) Safety, n (%) N=35 ≥1 AE 33 (94.3) Grade 3-5 AEs 19 (54.3) AE-related deaths 4 (11.4) Serious AEs 13 (37.1) AEs leading to withdrawal from study 4 (11.4) Treatment-related AEs 25 (71.4) Treatment-related AEs leading to withdrawal from study 1 (2.9) *By tumor type: non-small cell lung cancer (n=1), breast (n=3), and endometrial (n=1); †Six patients had missing data due to: death (n=4), clinical progression (n=1), or withdrawal of consent (n=1) prior to first scan; ‡Criteria for clinical benefit: either a response (confirmation not required) and/or stable disease or better for at least 24 weeks. AE, adverse event; CI, confidence interval; NE, not estimable. Citation Format: Jeong Eun Kim, David Thomas, Shirish Gadgeel, Marcelo Corassa, Tira J. Tan, Eugenia Girda, Donald Richards, Sabine Tejpar, David Chen, Junhan Fang, Sid Patel, Timothy R. Wilson, Fabrice Barlesi. Trastuzumab emtansine in patients (pts) with HER2 mutation-positive (HER2mut) tumors: TAPISTRY study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT265.