DESTINY‑PanTumor02 final analysis reinforces clinical positioning of trastuzumab deruxtecan (Enhertu) in HER2‑positive endometrial cancer and solid tumors

On 13 April 2026, AstraZeneca and Daiichi Sankyo (AZ/DSI) shared an encore presentation of the final analysis from Part 1 of the Phase 2 DESTINY‑PanTumor02 trial (NCT04482309). The study enrolled patients with multiple solid tumors, including gynecological malignancies such as endometrial cancer (EC), and supported the accelerated approval of trastuzumab deruxtecan (T‑DXd; Enhertu), a HER2‑directed antibody–drug conjugate, for previously treated HER2‑positive (IHC 3+) solid tumor patients.

The data were presented as an oral presentation at the 2026 Society of Gynecologic Oncology (SGO) Annual Meeting and had previously been shared as a poster at ESMO 2025. According to AZ/DSI, the encore presentation reinforced several key elements of the current scientific and clinical messaging around the accessibility and utility of T‑DXd in the second line and beyond for HER2‑expressing tumors.

Final results confirmed consistent anti‑tumor activity in patients with HER2‑expressing disease regardless of whether HER2 status was determined by central or local testing. No new safety signals were observed compared with prior primary and post‑hoc analyses, supporting the established safety profile of T‑DXd. Efficacy outcomes continued to correlate with HER2 expression levels, with the greatest clinical benefit observed in patients with IHC 3+ tumors.

Based on these outcomes, AZ/DSI have advanced the clinical development of T‑DXd into earlier lines of therapy in endometrial cancer. Two Phase 3 trials have recently been initiated: DESTINY‑Endometrial01, evaluating T‑DXd in combination with pembrolizumab or rilvegostomig in the first‑line setting, and DESTINY‑Endometrial02, investigating T‑DXd as neoadjuvant therapy in HER2‑positive (IHC 3+/2+) EC patients.

From a competitive and guideline perspective, T‑DXd represents a direct competitor to sacituzumab govitecan (Trodelvy) in the second‑line and later EC setting. T‑DXd is currently approved for HER2‑positive IHC 3+ solid tumors and is included in NCCN recommendations for IHC 2+ endometrial cancer patients in the second line. AZ/DSI anticipate that T‑DXd will remain the preferred therapeutic option for HER2‑positive IHC 3+/2+ patients, who represent approximately 30% of the 2L+ EC population, even in the context of potential future TROP‑2 ADC approvals for broader populations.

From a regulatory standpoint, AZ/DSI are awaiting a CHMP opinion for a European label expansion to HER2‑positive IHC 3+ solid tumors, with an opinion expected in mid‑2026 and a potential EU launch in the second half of 2026. In parallel, Part 2 of DESTINY‑PanTumor02, which enrolled patients with lower HER2 expression (IHC 2+/1+), has completed recruitment. Preliminary data from this cohort may support a future accelerated approval in these populations, with initial results anticipated in the second half of 2026.

Link: https://clinicaltrials.gov/study/NCT04482309