MyPathway HER2 basket study: Pertuzumab (P) + trastuzumab (H) treatment of a large, tissue-agnostic cohort of patients with HER2-positive advanced solid tumors.

person Funda Meric-Bernstam Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX info_outline Funda Meric-Bernstam, John Hainsworth, Ron Bose, Howard A. Burris III, Claire Frances Friedman, Razelle Kurzrock, Charles Swanton, Yong Wang, Jonathan Levy, Katja Schulze, Richard Price, Arisha Patel, Christopher Sweeney

Authors person Funda Meric-Bernstam Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX info_outline Funda Meric-Bernstam, John Hainsworth, Ron Bose, Howard A. Burris III, Claire Frances Friedman, Razelle Kurzrock, Charles Swanton, Yong Wang, Jonathan Levy, Katja Schulze, Richard Price, Arisha Patel, Christopher Sweeney Organizations Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, Sarah Cannon Research Institute and Tennessee Oncology, PLLC, Nashville, TN, Washington University School of Medicine in St. Louis, St. Louis, MO, Memorial Sloan Kettering Cancer Center, New York, NY, Moores Cancer Center, UC San Diego, San Diego, CA, Francis Crick Institute and UCL Hospitals, London, United Kingdom, Genentech, Inc., South San Francisco, CA, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA Abstract Disclosures Research Funding Pharmaceutical/Biotech Company F. Hoffmann-La Roche/Genentech Background: HER2 ( ERBB2 ) amplification and/or overexpression is observed in 2–3% of solid tumors, and is often associated with more aggressive disease. Thus far, HER2-targeted therapies are FDA-approved only for breast, gastric, and gastroesophageal cancers. MyPathway (NCT02091141) is a non-randomized, phase 2a multi-basket study assessing the activity of FDA-approved targeted therapies in non-indicated advanced solid tumors with relevant molecular alterations. We report results from the MyPathway HER2 basket, comprising a large, tissue-agnostic cohort of patients (pts) with HER2-altered tumors treated with P + H. Methods: Pts in this analysis were aged ≥18 years and had HER2-amplified and/or overexpressed tumors. Pts received P (840-mg IV loading dose, then 420-mg every 3 weeks [q3w]) + H (8-mg/kg IV loading dose, then 6-mg/kg q3w). The primary efficacy endpoint was investigator-assessed objective response rate (ORR). Other endpoints included disease control rate (DCR, defined by objective response or stable disease >4 mos) and duration of response (DOR). Subgroup analyses were completed by tumor type and KRAS status. Results: Pts were fully enrolled from April 14, 2014 to June 15, 2020. By January 22, 2021, 260 pts were efficacy-evaluable. Confirmed ORR (cORR) was 23.1% (60/260, including 5 complete responses; 95% confidence interval [CI] 18.1–28.7), DCR was 44.2% (115/260, 95% CI 38.1–50.5), and median DOR was 7.9 mos (95% CI 6.2–9.3). In 199 pts with wild-type KRAS tumors, cORR was 25.6% (51/199, 95% CI 19.7–32.3), DCR was 48.7% (97/199, 95% CI 41.6–55.9), and median DOR was 8.3 mos (95% CI 6.2–10.8). In comparison, in 26 pts with KRAS -mutated tumors, cORR was 3.8% (1/26, responder had colorectal cancer; 95% CI 0.1–19.6), DCR was 3.8% (1/26, 95% CI 0.1–19.6), and DOR was 2.7 mos. KRAS status was unknown in 35/260 pts (cORR 22.9% [8/35, 95% CI 10.4–40.1]; median DOR 6.7 mos [95% CI 2.5–12.7]). Clinical outcomes by tumor type are shown in the Table. Conclusions: P+H was active in a wide variety of KRAS wild-type HER2-amplified/overexpressed tumor types, but had limited activity in KRAS -mutated tumors. Clinical trial information: NCT02091141 Tumor type cORR n/n (%) 95% CI cORR: KRAS WT n/n (%) 95% CI DOR: KRAS WT Median mos 95% CI Colorectal n=84 22/84 (26.2) 17.2–36.9 21/68 (30.9) 20.2–43.3 5.9 4.2–8.5 Biliary n=40 9/40 (22.5) 10.8–38.5 9/35 (25.7) 12.5–43.3 8.5 7.0–18.9 Non-small cell lung n=27 7/27 (25.9) 11.1–46.3 5/20 (25.0) 8.7–49.1 8.3 5.6–not evaluable [NE] Uterine n=23 1/23 (4.3) 0.1–21.9 1/16 (6.3) 0.2–30.2 15.4 (1 responder) Urothelial n=22 4/22 (18.2) 5.2–40.3 3/18 (16.7) 3.6–41.4 24.2 7.9–44.9 Salivary n=18 11/18 (61.1) 35.7–82.7 7/11 (63.6) 30.8–89.1 8.4 6.9–NE Ovarian n=12 1/12 (8.3) 0.2–38.5 1/10 (10.0) 0.3–44.5 6.9 (1 responder) Pancreas n=10 1/10 (10.0) 0.3–44.5 1/3 (33.3) 0.8–90.6 19.3 (1 responder) Other n=24 4/24 (16.7) 4.7–37.4 3/18 (16.7) 3.6–41.4 11.3 9.3–20.7