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News|Articles|June 10, 2025

First Patient Dosed in Phase III Trial of Enhertu as First-Line Treatment for Endometrial Cancer

In combination with rilvegostomig or Keytruda, Enhertu will be evaluated versus chemotherapy in the DESTINY-Endometrial01 study for the treatment of patients with HER2-expressing, mismatch repair proficient primary advanced or recurrent endometrial cancer.

Key takeaways

Phase III Trial Explores Enhertu Combo in Endometrial Cancer: DESTINY-Endometrial01 is assessing Enhertu with rilvegostomig or Keytruda vs. chemo plus Keytruda in HER2-expressing, pMMR endometrial cancer.

Study Reflects Growing Biomarker-Driven, Multi-Partner Designs: The global trial (600 patients) involves AstraZeneca, GOG Foundation, and ENGOT, highlighting industry collaboration and targeted therapy focus.

Strong Phase II Data Supports Phase III Goals: DESTINY-PanTumor02 showed a 57.5% ORR and 26-month median OS in endometrial cancer, setting high expectations for this trial’s outcomes.

Daiichi Sankyo announced the first patient has been dosed in the DESTINY-Endometrial01 clinical trial (NCT06989112) evaluating Enhertu (trastuzumab deruxtecan) in combination with rilvegostomig or Merck’s Keytruda (pembrolizumab) as a first-line treatment for patients with HER2-expressing (IHC 3+/ 2+), mismatch repair proficient (pMMR) primary advanced or recurrent endometrial cancer. The study is being conducted in collaboration with the GOG Foundation and the European Network of Gynecological Oncological Trial (ENGOT) groups.1

Trial design compares immunotherapy combinations against chemotherapy

The Phase III DESTINY-Endometrial01 trial is a global, multicenter, randomized, open-label study. It is evaluating the safety and efficacy of Enhertu in combination with rilvegostomig or Keytruda versus platinum-based chemotherapy (carboplatin and paclitaxel) alongside Keytruda. Patients will be randomized 1:1:1 to receive either Enhertu in combination with rilvegostomig, Enhertu in combination with Keytruda, or chemotherapy in combination with Keytruda.

Alongside Enhertu and Keytruda in the treatment arms of the study, rilvegostomig is a PD-1/TIGIT bispecific antibody being investigated by AstraZeneca. The TIGIT component is derived from the clinical-stage anti-TIGIT antibody, COM902, developed by Compugen. In February 2023, Compugen announced it would be progressing rilvegostomig into Phase III research along with an expanded Phase II development program.2

Study endpoints focus on survival and response metrics

DESTINY-Endometrial01 is being sponsored by AstraZeneca and has an estimated enrollment of 600 patients. The primary endpoint is progression-free survival (PFS) assessed by blinded independent central review. The key secondary endpoint is overall survival (OS), with other secondary measures including PFS assessed by investigator, objective response rate (ORR), duration of response, and safety.3

In a press release, Mark Rutstein, MD, head, therapeutic area oncology development, Daiichi Sankyo, said: “Following the positive results in the endometrial cancer cohort of DESTINY-PanTumor02, which contributed to a tumor agnostic approval for previously treated patients with HER2 positive metastatic tumors in several regions, we are initiating this first Phase III trial of Enhertu in the first-line setting of advanced endometrial cancer. The DESTINY-Endometrial01 trial will help us better understand the role of Enhertu in combination with immunotherapy as a potential treatment strategy to help improve outcomes compared to the current standard of care in this specific gynecological cancer setting.”1

DESTINY-PanTumor02 trial demonstrated encouraging efficacy in HER2-expressing tumors

As mentioned by Rutstein, Daiichi Sankyo and AstraZeneca saw positive results from Enhertu in the Phase II DESTINY-PanTumor02 trial (NCT04482309), which evaluated the therapy across multiple HER2-expressing advanced solid tumors including biliary tract, bladder, cervical, endometrial, ovarian, and pancreatic cancers. In October 2023, the companies shared that Enhertu demonstrated clinically meaningful and durable responses in the trial, leading to a clinically meaningful survival benefit.4

In this primary analysis of DESTINY-PanTumor02, Enhertu demonstrated a median PFS of 6.9 months and a median OS of 13.4 months in the overall trial population. In the endometrial cancer arm, Enhertu showed a confirmed ORR of 57.5%, a median PFS of 11.1 months, and a median OS of 26 months, across all IHC expression levels.

In a press release from the time, Rutstein said: “Improving survival outcomes for patients is one of the primary goals of cancer treatment and the clinically meaningful progression-free and overall survival results seen in DESTINY-PanTumor02 are encouraging. These results provide additional evidence for Enhertu to potentially become the first antibody drug conjugate approved in a tumor-agnostic setting in patients whose tumors express HER2.”

DESTINY-PanTumor02 is an open-label, multicenter, multi-cohort study evaluating the efficacy and safety of Enhertu for the treatment of selected HER2-expressing tumors. This trial is also sponsored by AstraZeneca and the estimated enrollment stands at 468 patients.5

References

1. DESTINY-Endometrial01 Phase 3 Trial of ENHERTU® Initiated as First-Line Therapy in Patients with HER2 Expressing Primary Advanced or Recurrent Endometrial Cancer. News release. Daiichi Sankyo. June 9, 2025. Accessed June 10, 2025. https://www.businesswire.com/news/home/20250606922315/en/DESTINY-Endometrial01-Phase-3-Trial-of-ENHERTU-Initiated-as-First-Line-Therapy-in-Patients-with-HER2-Expressing-Primary-Advanced-or-Recurrent-Endometrial-Cancer

2. Rilvegostomig, AstraZeneca's Bi-specific Antibody Derived from Compugen's COM902, Expected to Progress into Phase 3. News release. Compugen. February 14, 2023. Accessed June 10, 2025. https://www.prnewswire.com/news-releases/rilvegostomig-astrazenecas-bi-specific-antibody-derived-from-compugens-com902-expected-to-progress-into-phase-3-301746238.html

3. DESTINY-Endometrial01: A Phase III Study of Trastuzumab Deruxtecan Plus Rilvegostomig or Pembrolizumab as First-Line Treatment of HER2-Expressing (IHC 3+/​2+), Mismatch Repair Proficient (pMMR) Endometrial Cancer (DE-01). ClinicalTrials.gov. Accessed June 10, 2025. https://clinicaltrials.gov/study/NCT06989112?term=DESTINY-Endometrial01&rank=1

4. ENHERTU® (fam-trastuzumab deruxtecan-nxki) Demonstrated Clinically Meaningful Survival Across Multiple HER2-Expressing Advanced Solid Tumors in DESTINY-PanTumor02 Phase II Trial. News release. AstraZeneca. October 23, 2023. Accessed June 10, 2025. https://www.businesswire.com/news/home/20231023650458/en/ENHERTU-fam-trastuzumab-deruxtecan-nxki-Demonstrated-Clinically-Meaningful-Survival-Across-Multiple-HER2-Expressing-Advanced-Solid-Tumors-in-DESTINY-PanTumor02-Phase-II-Trial

5. A Phase 2 Study of T-DXd in Patients With Selected HER2 Expressing Tumors (DPT02). ClinicalTrials.gov. Accessed June 10, 2025. https://clinicaltrials.gov/study/NCT04482309

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