MyPathway Human Epidermal Growth Factor Receptor 2 Basket Study: Pertuzumab 1 Trastuzumab Treatment of a Tissue-Agnostic Cohort of Patients With Human Epidermal Growth Factor Receptor 2–Altered Advanced Solid Tumors

The MyPathway multiple-basket study (ClinicalTrials.gov identifier: NCT02091141) is evaluating targeted therapies in nonindicated tumors with relevant molecular alterations. We assessed pertuzumab 1 trastuzumab in a tissue-agnostic cohort of adult patients with human epidermal growth factor receptor 2 (HER2)–amplified and/or –overexpressed and/or –mutated solid tumors. The primary end point was objective response rate (ORR); secondary end points included survival and safety. At data cutoff (March 2022), 346 patients with HER2 amplification and/or overexpression with/without HER2 mutations (n 5 263), or HER2 mutations alone (n 5 83) had been treated. Patients with HER2 amplification and/or overexpression had an ORR of 25.9% (68/263, 95% CI, 20.7 to 31.6), including five complete responses (urothelial [n 5 2], salivary gland [n 5 2], and colon [n 5 1] cancers). Activity was higher in those with wild-type (ORR, 28.1%) versus mutated KRAS (ORR, 7.1%). Among patients with HER2 amplification, ORR was numerically higher in patients with immunohistochemistry (IHC) 31 (41.0%; 32/78) or 21 (21.9%; 7/32), versus 11 (8.3%; 1/12) or no expression (0%; 0/20). In patients with HER2 mutations alone, ORR was 6.0% (5/83, 95% CI, 2.0 to 13.5). Pertuzumab 1 trastuzumab showed activity in various HER2-amplified and/or -overexpressed tumors with wild-type KRAS, with the range of activity dependent on tumor type, but had limited activity in the context of KRAS mutations, HER2 mutations alone, or 0-11 HER2 expression.