On December 9, 2025 Daiichi Sankyo reported that the first patient has been dosed in the randomization phase of the DESTINY-Ovarian01 phase 3 trial evaluating ENHERTU (trastuzumab deruxtecan) in combination with bevacizumab versus bevacizumab monotherapy as first-line maintenance therapy in patients with HER2 expressing (IHC 3+/2+/1+) advanced high-grade epithelial ovarian cancer following treatment with first-line platinum-based chemotherapy in combination with bevacizumab.

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DESTINY-Ovarian01 is being conducted in collaboration with the European Network of Gynecological Oncological Trial Groups (ENGOT), with the Spanish cooperative group (GEICO) as the lead ENGOT group, The GOG Foundation, Inc. (GOG-F) and Asia-Pacific Gynecologic Oncology Trials Group (APGOT).

ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).

The prognosis for patients with ovarian cancer is poor with an estimated five-year survival rate of 31.8% for those with advanced disease.1 Approximately 70% to 80% of patients with advanced ovarian cancer (Stage 3 or 4) will experience disease recurrence following standard treatment with surgery and platinum-based chemotherapy regimens.2 Maintenance therapy may be given to delay relapse and current recommended treatment strategies include bevacizumab or PARP inhibitor monotherapy or bevacizumab/PARP inhibitor combination treatment, depending on the biomarker status of the tumor. 3 There currently are no HER2 directed medicines approved as maintenance therapy despite HER2 expression being present in up to 55% of ovarian cancers.

"Results from the ovarian cancer cohort of DESTINY-PanTumor02 demonstrated clinically meaningful and durable responses in previously treated patients with HER2 expressing advanced ovarian cancer, supporting the development of ENHERTU in earlier lines of therapy," said Abderrahmane Laadem, MD, Head, Late- 2 Stage Oncology Clinical Development, Daiichi Sankyo. "Given the important role first-line maintenance therapy can play in disease control, we have initiated this first phase 3 trial in ovarian cancer to evaluate whether ENHERTU combined with bevacizumab could become a new maintenance strategy for patients with HER2 expressing advanced high-grade epithelial ovarian cancer."

About DESTINY-Ovarian01

DESTINY-Ovarian01 is a global, multicenter, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) in combination with bevacizumab versus bevacizumab monotherapy as first-line maintenance therapy in patients with HER2 expressing (IHC 3+/2+/1+) advanced high-grade epithelial ovarian cancer following treatment with first-line platinum-based chemotherapy in combination with bevacizumab. The randomized period of the trial was preceded by a non-randomized safety run-in phase to evaluate the safety of ENHERTU in combination with bevacizumab.

The primary endpoint is progression-free survival (PFS) as assessed by blinded independent central review (BICR) in the HER2 IHC 3+/2+ population. The key secondary endpoint is overall survival (OS) in the HER2 IHC 3+/2+ population. Additional secondary endpoints include PFS as assessed by BICR and OS in the HER2 IHC 3+/2+/1+ population as well as PFS as assessed by investigator in both the HER2 IHC 3+/2+ and HER2 IHC 3+/2+/1+ populations.

DESTINY-Ovarian01 will enroll approximately 580 patients across multiple sites in Asia, Europe, North America and South America. For more information about the trial, visit ClinicalTrials.gov

About Ovarian Cancer

Ovarian cancer is the third most common gynecologic cancer and the seventh most common cancer among women worldwide. 7 More than 324,000 women were diagnosed with ovarian cancer worldwide in 2022.8 The prognosis for ovarian cancer is poor with an estimated five-year survival rate of 31.8% for those with advanced disease.1 Epithelial ovarian cancer accounts for approximately 90% of ovarian cancer cases and the majority are diagnosed at an advanced stage (Stage 3 or 4).

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors.10 HER2 expression (IHC 3+/2+/1+) is present in up to 55% of ovarian cancers and is associated with advanced stages, higher frequency of recurrence, shorter survival time and lower response to platinum-based chemotherapy.

Approximately 70% to 80% of patients with advanced ovarian cancer (Stage 3 or 4) will experience disease recurrence following standard treatment with surgery and platinum-based chemotherapy regimens.2 Maintenance therapy may be given to delay relapse and current recommended treatment strategies include 3 bevacizumab or PARP inhibitor monotherapy or bevacizumab/PARP inhibitor combination treatment, depending on the biomarker status of the tumor. 3 As a majority of patients will experience disease progression on or after these therapies, new treatment strategies are needed. 12,13,14,15 Currently, there are no HER2 targeted medicines approved as first-line maintenance therapy for patients with HER2 expressing advanced epithelial ovarian cancer.

About ENHERTU

ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

ENHERTU (5.4 mg/kg) is approved in more than 90 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (immunohistochemistry [IHC] 3+ or in-situ hybridization [ISH]+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.

ENHERTU (5.4 mg/kg) is approved in more than 85 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

ENHERTU (5.4 mg/kg) is approved in more than 45 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic hormone receptor (HR) positive, HER2 low (IHC 1+ or IHC 2+/ISH- ) or HER2 ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that have progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial.

ENHERTU (5.4 mg/kg) is approved in more than 60 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the U.S. for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ENHERTU (6.4 mg/kg) is approved in more than 70 countries/regions worldwide for the treatment of adult patients with locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Continued approval in China for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ENHERTU (5.4 mg/kg) is approved in more than 10 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

About the ENHERTU Clinical Development Program

A comprehensive global clinical development program is underway evaluating the efficacy and safety of ENHERTU as a monotherapy or in combination or sequentially with other cancer medicines across multiple HER2 targetable cancers.

(Press release, Daiichi Sankyo, DEC 9, 2025, View Source [SID1234665025])