A Phase 2 Basket Trial of Ado-Trastuzumab Emtansine for Patients with HER2 Amplified Cancers: A Non-Randomized Clinical Trial
PURPOSE: To evaluate the efficacy of ado-trastuzumab emtansine (T-DM1) among patients with advanced/metastatic HER2-amplified solid tumors. PATIENTS AND METHODS: This was a single-center, non-randomized phase 2 basket trial conducted at Memorial Sloan Kettering Cancer Center. All 95 patients had HER2-amplified metastatic/advanced disease and were enrolled in 1 of 5 cohorts. HER2 amplification was diagnosed either with next-generation sequencing or in-situ hybridization. All patients received intravenous T-DM1 3.6 mg/kg every 21 days. The primary endpoint was overall response rate (ORR). Overall survival (OS), progression-free survival (PFS), duration of response (DOR), and safety were secondary endpoints. RESULTS: We treated 95 patients, and 22 (23% [95% CI, 16-33%]) had a confirmed response by investigator assessment. The investigator-assessed confirmed ORRs by cohort were: salivary 11/19 (58% [95% CI, 36-77%]); lung 4/23 (17% [95% CI, 7-37%]); colorectal 0/7 (0% [95% CI, 0-35%]); endometrial 5/23 (22% [95% CI, 10-42%]); "other" 2/23 (9% [95% CI, 2-27%]). Median PFS was 3.6 months (95% CI, 2.6-5.4) and ranged from 1.4 months in the "other" cohort to 10.2 months in the salivary cohort. Median OS was 11.9 months (95% CI, 8.4-17.2) and ranged from 7.8 months in the "other" cohort to 29.2 months in the salivary cohort. Median DOR was 13.1 months (95% CI, 7.3-30.5), ranging from 6.4 months in the lung cohort to 18.4 months in the "other" cohort. CONCLUSIONS: T-DM1 demonstrated heterogenous efficacy among HER2-amplified tumor types, with promising response and outcomes among patients with salivary gland cancer.
Authors
- Jessica C. Stuart (ORCID: https://orcid.org/0000-0001-8770-6425)
- Michelle S. Ginsberg (ORCID: https://orcid.org/0000-0003-0304-110X)
- Kanika S. Arora (ORCID: https://orcid.org/0000-0001-9537-8708)
- Vetri Sudar Jayaprakasam (ORCID: https://orcid.org/0000-0002-7360-9867)
- Mark Dunphy (ORCID: https://orcid.org/0000-0002-1886-1832)
- Mark Jeng (ORCID: https://orcid.org/0000-0003-0854-761X)
- Nora Katabi (ORCID: https://orcid.org/0000-0003-2974-3046)
- Alan Loh Ho (ORCID: https://orcid.org/0000-0002-6885-3742)
- Michael F. Berger (ORCID: https://orcid.org/0000-0003-3882-5000)
- Amanda Johnson (ORCID: https://orcid.org/0000-0001-7774-281X)
- Rona Yaeger (ORCID: https://orcid.org/0000-0002-7233-5454)
- Mark G. Kris (ORCID: https://orcid.org/0000-0002-7317-5341)
- Bob T. Li (ORCID: https://orcid.org/0000-0001-6661-8733)
- Jonathan Loi (ORCID: https://orcid.org/0000-0001-5229-2293)
- Ronglai Shen (ORCID: https://orcid.org/0000-0001-9694-584X)
- Winston Wong (ORCID: https://orcid.org/0000-0002-5144-6542)
- Gregory J. Riely (ORCID: https://orcid.org/0000-0001-5357-4313)
- Alexander Edward Dela Cruz Drilon (ORCID: https://orcid.org/0000-0001-6806-9061)
- Gopa Iyer (ORCID: https://orcid.org/0000-0002-5093-6099)
- Lauren Schoech (ORCID: https://orcid.org/0000-0003-2727-467X)
- Vicky Makker (ORCID: https://orcid.org/0000-0001-9793-7614)
- Alex Makhnin (ORCID: https://orcid.org/0000-0003-1998-7274)
- Charles Hsu (ORCID: https://orcid.org/0000-0003-1036-9015)
- Jamie E. Chaft (ORCID: https://orcid.org/0000-0002-5838-9982)
- Dazhi Liu (ORCID: https://orcid.org/0000-0003-3296-8203)
- David B. Solit (ORCID: https://orcid.org/0000-0002-6614-802X)
- Ranieri Yllanes
- Ala'A Damrah (ORCID: https://orcid.org/0009-0007-7061-9107)
Institutions
- Memorial Sloan Kettering Cancer Center (US)
Publication Details
- Journal
- Clinical Cancer Research
- Published
- 2026-08-27
- DOI
- https://doi.org/10.1158/1078-0432.ccr-26-1566
- Primary Topic
- HER2/EGFR in Cancer Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00