A pragmatic, hybrid observational study evaluating the effectiveness of trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) 3+ solid tumors: DESTINY-PanTumor04.

Abstract

TPS11202 Background: Patients with advanced or metastatic HER2 IHC 3+ solid tumors have limited treatment options beyond first-line settings, with generally poor outcomes. T-DXd is a HER2-directed antibody-drug conjugate approved in multiple countries, including in the US for patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior treatment and have no satisfactory alternative therapies. Building on existing clinical trial data, DESTINY-PanTumor04 evaluates the real-world effectiveness of T-DXd in HER2-positive (IHC 3+) solid tumors, using a hybrid data collection approach that enhances efficiency for sites and physicians and facilitates study implementation. Methods: DESTINY-PanTumor04 (NCT07124000) is a multicenter, pragmatic observational, real-world study evaluating the effectiveness of T-DXd (5.4 mg/kg IV Q3W) in adult patients in the US with previously treated, locally advanced, unresectable, or metastatic HER2-positive (IHC 3+ by local testing) solid tumors. Data collection will use a hybrid approach, combining primary data collection of baseline tumor burden, comorbidities, ECOG status, treatment response, and survival, with secondary data collection from electronic health record (EHR) abstraction for all other data. Approximately 100 patients will be enrolled across US sites, including community oncology practices and academic medical centers within an existing US oncology network from Paradigm Health. Participating sites will use technological resources that support the identification of eligible patients and enable efficient EHR-to-electronic data capture and transfer, minimizing physician time while improving compliance in data completeness and accuracy. Eligible patients must have disease progression following ≥1 prior systemic treatment for metastatic or advanced disease, have no alternative treatment options, and have a clinical decision for T-DXd treatment in accordance with the FDA label. Patients with breast cancer, colorectal cancer, non-small cell lung cancer, gastric or gastroesophageal junction cancers, or hematologic malignancies will be excluded. Primary endpoints are real-world objective response rate, defined as the proportion of patients with a complete response (CR) or partial response (PR) as determined by clinician assessment per criteria used in routine clinical practice; and real-world duration of response, defined as the time from first objective response (CR or PR) to disease progression as determined by clinician assessment per criteria used in routine clinical practice, or death. Secondary endpoints include real-world time to treatment discontinuation and real-world time to next treatment. Enrollment began in September 2025 and is ongoing. Clinical trial information: NCT07124000 .