Abstract CT249: An open-label, multicenter, phase 2 study of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-expressing solid tumors: DESTINY-PanTumor02 (DP-02) Part 2

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Abstract Background: T-DXd is a HER2-directed antibody-drug conjugate that is approved in multiple countries for the treatment of HER2-positive and HER2-low breast cancer, HER2-positive gastric or gastroesophageal junction adenocarcinoma, and HER2-mutant non-small cell lung cancer (NSCLC). In April 2024, T-DXd received accelerated approval in the US for adult pts with unresectable or metastatic HER2-positive (immunohistochemistry [IHC] 3+) solid tumors that have progressed after prior systemic treatment and have no satisfactory alternative therapies. In Part 1 of the DP-02 study (N=267), T-DXd showed clinically meaningful investigator-assessed (INV) objective response rates (ORRs; 37.1% [95% CI 31.3, 43.2]) and INV median progression-free survival (PFS; 6.9 months [95% CI 5.6, 8.0]) in pretreated pts with HER2-expressing solid tumors, with the largest effect observed in pts with centrally confirmed HER2 IHC 3+ tumors (ORR 61.3% [95% CI 49.4, 72.4]; median PFS 11.9 months [95% CI 8.2, 13.0]); safety was consistent with the known profile. Here, we describe Part 2 of the DP-02 study. Methods: DP-02 (NCT04482309) is an open-label, multicenter, Phase 2 study evaluating T-DXd (5.4 mg/kg intravenously once every 3 weeks) in pts with HER2-expressing locally advanced or metastatic solid tumors that have progressed following prior systemic treatment or have no alternative treatment options. Part 2 will enroll ∼40 pts in each of the following cohorts: A, any HER2 IHC 3+ tumor; B, any HER2 IHC 2+ / in situ hybridization-positive tumor; C, HER2 IHC 2+/1+ endometrial cancer; D, HER2 IHC 2+/1+ ovarian cancer; or E, HER2 IHC 2+/1+ cervical cancer. Pts with breast, gastric, or colorectal cancer will not be enrolled; unlike in Part 1, pts with NSCLC will be eligible for cohorts A and B. HER2 expression will be determined by central testing and scored per ASCO/CAP gastric-specific criteria. The primary endpoint is INV confirmed ORR per RECIST 1.1. Secondary endpoints include duration of response, disease control rate, PFS, and overall survival. Safety, tolerability, pharmacokinetics, and immunogenicity will also be assessed. Previously presented at ESMO Asia 2024; Final Publication Number: 400 TiP; Jung-Yun Lee et al. Reused with permission Citation Format: Funda Meric-Bernstam, Jung-Yun Lee, Vicky Makker, Ana Oaknin, Chiedozie Anoka, Lindsey Jung, Soham Puvvada, João Simões, Do Youn Oh. An open-label, multicenter, phase 2 study of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-expressing solid tumors: DESTINY-PanTumor02 (DP-02) Part 2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT249.

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