Trastuzumab deruxtecan (T-DXd) for pretreated patients in China with HER2 IHC 3+ solid tumors: DESTINY-PanTumor03 Part 1 primary analysis.

Abstract

3026 Background: Treatment options in China are limited for patients with late-line, HER2-expressing advanced solid tumors. In Part 1 of DESTINY-PanTumor02, T-DXd showed clinically meaningful antitumor activity in HER2-expressing advanced solid tumors, with the greatest benefit observed in HER2 IHC 3+ tumors. Based in part on these findings, T-DXd has been approved in multiple countries worldwide, including the US, as treatment for patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior treatment and/or have no satisfactory alternative therapies. Following the results from DESTINY-PanTumor02, DESTINY-PanTumor03 is evaluating T-DXd in patients in China with HER2-expressing advanced solid tumors. The primary analysis of Part 1 of DESTINY-PanTumor03 is presented here. Methods: DESTINY-PanTumor03 is an open-label, Phase 2 study (NCT06271837). Part 1 is evaluating T-DXd (5.4 mg/kg IV Q3W) in patients in China with HER2 IHC 3+ (by central testing), locally advanced, unresectable, or metastatic solid tumors (excluding breast and gastric cancers) after ≥1 prior systemic treatment for advanced disease or without treatment options. The primary endpoint is confirmed objective response rate (ORR) by independent central review (ICR) per RECIST 1.1. Secondary endpoints include ORR by investigator assessment (INV) per RECIST 1.1; duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS) by INV and ICR per RECIST 1.1; overall survival (OS); and safety. Results: At primary analysis data cutoff (November 28, 2025), 50 patients with biliary tract (n = 11), colorectal (n = 6), cervical (n = 10), endometrial (n = 7), ovarian (n = 5), non-small cell lung (n = 7), or other cancers (n = 4) had received T-DXd. Median follow-up duration was 9.9 (range 1.1–18.3) months. Median number of prior treatment regimens was 2 (range 1–10). By ICR, ORR (95% CI) was 58.0% (43.2, 71.8), median DOR (95% CI) was 15.4 (12.5, not evaluable [NE]) months, DCR (95% CI) at Week 6 was 88.0% (75.7, 95.5), and median PFS (95% CI) was 15.7 (7.2, NE) months. By INV, ORR (95% CI) was 56.0% (41.3, 70.0). Median OS was not reached. Grade ≥3 drug-related adverse events occurred in 31 (62.0%) patients, and adjudicated drug-related interstitial lung disease / pneumonitis occurred in 4 (8.0%) patients (Grade 2 n = 3 [6.0%], Grade 3 n = 1 [2.0%]). Conclusions: T-DXd demonstrated durable and clinically meaningful antitumor activity in pretreated patients in China with HER2 IHC 3+ advanced solid tumors. Safety was generally consistent with the established T-DXd profile. Results from DESTINY-PanTumor03 Part 1 support T-DXd as a tumor-agnostic treatment for patients in China with HER2 IHC 3+ solid tumors. Clinical trial information: NCT06271837 .