Abstract CT209: DiscovHER PAN-206: Phase 2 tumor-agnostic study of zanidatamab in patients with previously treated human epidermal growth factor receptor 2-overexpressing solid tumors

Abstract Background: Tissue-agnostic HER2 targeting is a rational, precision-oncology approach for treating HER2-expressing tumors due to the protein’s expression across multiple tumor types and potential oncogenic role. Zanidatamab, a dual HER2-targeted bispecific antibody, is approved as monotherapy by the US Food and Drug Administration for adults with previously treated, unresectable or metastatic HER2-positive immunohistochemistry (IHC) 3+ biliary tract cancer (BTC) based on the phase 2 HERIZON-BTC-01 trial. In 62 patients with previously treated BTC, the confirmed objective response rate (cORR) was 52% and the median duration of response (DOR) was 14.9 months. Zanidatamab has also shown encouraging antitumor activity with a manageable safety profile in a phase 1 study of heavily pretreated patients with various HER2-expressing solid tumors. Methods: DiscovHER PAN-206 (NCT06695845) is an open-label, single-arm, multicenter study of zanidatamab monotherapy in adults with centrally assessed HER2 IHC 3+, locally advanced, unresectable or metastatic solid tumors (except BTC) who received ≥1 prior anticancer therapy and have no available treatment options with confirmed benefit. Eligible patients must have an Eastern Cooperative Oncology Group performance status of 0 or 1 and measurable disease by independent central review (ICR; per Response Evaluation Criteria in Solid Tumors version 1.1). Patients will be enrolled into 3 cohorts: cohort 1 (any solid tumor except breast cancer [BC] and gastroesophageal adenocarcinoma [GEA]), cohort 2 (BC), and cohort 3 (GEA). No prior HER2-targeted therapy is allowed for cohort 1; prior treatment with trastuzumab deruxtecan is required for cohorts 2 and 3. Zanidatamab will be administered intravenously once every 3 weeks at 1800 mg (patients <70 kg) or 2400 mg (patients ≥70 kg), until disease progression or unacceptable toxicity. The primary endpoint is cORR per ICR. Secondary endpoints include overall survival and frequency of adverse events; cORR per investigator; and DOR, time to response, disease control rate, and progression-free survival per ICR and investigator assessment. Exploratory endpoints include patient-reported outcomes. This trial is open for enrollment. Originally presented at the 2025 European Society for Medical Oncology Annual Meeting. Citation Format: Vivek Subbiah, Vicky Makker, Do-Youn Oh, Elizabeth Gardener, Elaina Gartner, Funda Meric-Bernstam. DiscovHER PAN-206: Phase 2 tumor-agnostic study of zanidatamab in patients with previously treated human epidermal growth factor receptor 2-overexpressing solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT209.