A phase 2, multicenter, open-label study evaluating trastuzumab deruxtecan (T-DXd) for the treatment of select human epidermal growth factor receptor 2 (HER2)-expressing solid tumors (DESTINY-PanTumor02).

TPS623 Background: Human epidermal growth factor receptor 2 (HER2) is an established therapeutic target in both breast and gastric cancer. However, HER2-targeting therapies are not approved beyond these malignancies despite a high prevalence of HER2 expression across cancers of epithelial origin. Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate consisting of an anti-HER2 antibody, a cleavable tetrapeptide-based linker, and a topoisomerase I inhibitor payload. In a cohort of pretreated patients with multiple HER2-expressing tumors, T-DXd demonstrated promising antitumor activity, with an investigator-assessed confirmed objective response rate of 40.9% (9 of 22 patients) and median progression-free survival of 11.1 months (95% CI, 5.4-20.5 months; Tsurutani J, et al. Cancer Discov. 2020;10:688-701). Here we describe the phase 2 DESTINY-PanTumor02 trial evaluating T-DXd in patients with select HER2-expressing solid tumors. Methods: DESTINY-PanTumor02 (NCT04482309) is an open-label, multicenter, multicohort, phase 2 study evaluating T-DXd for the treatment of patients with select HER2-expressing locally advanced, unresectable, or metastatic tumors. The study will consist of 7 cohorts of patients (n≈40 each) with urothelial bladder, biliary tract, cervical, endometrial, ovarian, pancreatic, or rare tumors (tumors excluding those in the other cohorts and breast, gastric, colorectal, and non-small cell lung cancer). Patients are required to have disease progression following ≥1 prior systemic treatment for advanced or metastatic disease or have no satisfactory alternative treatment options. Prior HER2-targeting therapy is allowed. The primary endpoint is investigator-assessed confirmed objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints include duration of response, disease control rate, progression-free survival (all per investigator assessment according to RECIST 1.1), overall survival, safety, pharmacokinetics, and immunogenicity. Previously presented at the ESMO Congress 2021, FPN: 1869 TiP, Meric-Bernstam et al. Reused with permission. Clinical trial information: NCT04482309.