Study of Trastuzumab Deruxtecan with Bevacizumab Versus Bevacizumab Monotherapy for First-line Maintenance in HER2-Expressing Ovarian Cancer (DO-01)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Daiichi Sankyo Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

11 Sep 2025 → ongoing

Decision date (initial)

2025-07-14

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Daiichi Sankyo, Inc.

External identifiers

EU CT number

2024-516982-35-00

ClinicalTrials.gov

NCT06819007

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy

To evaluate the safety and tolerability of T-DXd in combination with bevacizumab (for Safety Run-in phase).
To compare the efficacy of T-DXd in combination with bevacizumab (Arm A) versus bevacizumab monotherapy (Arm B) as measured by PFS, as assessed by BICR in the HER2 IHC 3+/2+ population (for Randomized phase).

Secondary objectives 17

1. To compare the efficacy of Arm A versus Arm B as measured by Overall Survival (OS) in the HER2 IHC 3+/2+ population.
2. To compare the efficacy of Arm A versus Arm B as measured by Progression Free Survival (PFS), as assessed by BICR in the HER2 IHC 3+/2+/1+ population.
3. To compare the efficacy of Arm A versus Arm B as measured by Overall Survival (OS) in the HER2 IHC 3+/2+/1+ population.
4. To evaluate the efficacy of Arm A versus Arm B as measured by Progression Free Survival (PFS), as assessed by the investigator in HER2 IHC 3+/2+ population.
5. To evaluate the efficacy of Arm A versus Arm B as measured by Progression Free Survival (PFS), as assessed by the investigator in the HER2 IHC 3+/2+/1+ population.
6. To evaluate the efficacy of Arm A versus Arm B as measured by Progression Free Survival (PFS2) in HER2 IHC 3+/2+ population.
7. To evaluate the efficacy of Arm A versus Arm B as measured by PFS2 in HER2 IHC 3+/2+/1+ population.
8. To evaluate the efficacy of Arm A versus Arm B as measured by Objective Response (OR) , as assessed by BICR in HER2 IHC 3+/2+ population.
9. To evaluate the efficacy of Arm A versus Arm B as measured by Objective Response (OR), as assessed by BICR in HER2 IHC 3+/2+/1+ population.
10. To evaluate the efficacy of Arm A versus Arm B as measured by Duration of Response (DoR), as assessed by BICR in HER2 IHC 3+/2+ population.
11. To evaluate the efficacy of Arm A versus Arm B as measured by (DoR), as assessed by BICR in HER2 IHC 3+/2+/1+ population.
12. To evaluate the efficacy of Arm A versus Arm B as measured by Time to First Subsequent Therapy (TFST) in HER2 IHC 3+/2+ population.
13. To evaluate the efficacy of Arm A versus Arm B as measured by Time to First Subsequent Therapy (TFST) in HER2 IHC 3+/2+/1+ population.
14. To evaluate the efficacy of Arm A versus Arm B as measured by Time to Second Subsequent Therapy (TSST) in HER2 IHC 3+/2+ population.
15. To evaluate the efficacy of Arm A versus Arm B as measured by Time to Second Subsequent Therapy (TSST) in HER2 IHC 3+/2+/1+ population.
16. To evaluate safety and tolerability of Arm A versus Arm B.
17. To evaluate patient reported outcomes for overall health status, functioning, and symptom burden in participants treated with Arm A versus Arm B.

Conditions and MedDRA coding

Ovarian Cancer

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Sign and date the tissue pre-screening ICF, prior to HER2 central testing. Sign and date the main ICF, prior to the start of any trial- specific qualification procedures. Consent to optional PGx prior to any PGx procedures. For participants in the safety run-in phase, a safety run-in ICF needs to be signed and dated prior to the start of any trial-specific qualification procedures.
2. Adults ≥18 years of age on the day of signing the ICF. Follow local regulatory requirements if the legal age of consent for trial participation is >18 years old.
3. Has histologically confirmed diagnosis of epithelial high-grade ovarian, fallopian tube or primary peritoneal carcinoma per local assessment (including but not limiting to serous, endometrioid, clear cell, carcinosarcoma, mucinous).
4. Is newly diagnosed FIGO Stage III or IV.
5. Has HER2 expression per IHC scoring (3+/2+/1+) guidelines by prospective central testing. For participants in the safety run-in phase, HER2 expression assessed by either local (require using IHC scoring [IHC 3+/2+/1+] guidelines) or central assessment (if available) is acceptable. Submission of the pathology report is required for participants enrolled based on local HER2 IHC results.
6. Has adequate tumor tissue sample available for assessment of HER2 by central laboratory. Tumor tissue block or sufficient tissue slides are required for HER2 testing and retrospective HRD status determination. Note: Participants in the safety run-in phase who are enrolled based on local HER2 IHC results are recommended to provide a tumor tissue sample from the same specimen for central assessment.
7. Has a local HRD or BRCA test result available. Participants with BRCA wildtype will have a local HRD test results, as applicable.
8. Has received up to 6 cycles of standard of care bevacizumab in combination with front line platinum based chemotherapy as per approved indication and clinical guidelines and is eligible to continue single agent bevacizumab maintenance per standard of care and investigator discretion.

Exclusion criteria 11

1. Has ovarian, fallopian tube, or peritoneal cancer of non-epithelial origin.
2. Has a known or suspected deleterious BRCA alteration as per local test that makes the patient eligible for PARP inhibitor treatment.
3. Participant to receive PARP inhibitor as maintenance per standard of care and investigator discretion. Reasons for which the participant is not eligible for PARP inhibitor will be recorded in the eCRF as follows: • HRD negative • HRD positive with SD as best response after platinum • HRD positive non-serous histology • HRD tested, but inconclusive • HRD positive but safety concern (safety concern to be specified).
4. Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug products and other monoclonal antibodies.
5. Previous Cerebral-Vascular Accident, Transient Ischemic Attack or Sub- Arachnoids Hemorrhage within 6 months prior to randomization.
6. Has evidence of bleeding diathesis or significant coagulopathy (in the absence of anticoagulation therapy).
7. Has a history of hemorrhagic disorders, abdominal fistula, gastrointestinal perforation, or active gastrointestinal bleeding within 6 months before randomization.
8. Evidence of active or ongoing bowel obstruction.
9. Has lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the trial randomization, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, pneumonectomy, etc.).
10. Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
11. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie pulmonary emboli within 3 months of the trial enrollment, severe asthma, severe COPD, restrictive lung disease, pleural effusion etc.), and any autoimmune, connective tissue or inflammatory disorders with potential pulmonary involvement (ie Rheumatoid arthritis, Sjogren's, sarcoidosis etc.), or prior pneumonectomy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression Free Survival by Blinded Independent Central Review (BICR) in the HER2 IHC 3+/2+ population Time from randomization to time of objective radiographic disease progression as assessed by BICR based on RECIST v1.1 or death due to any cause.

Secondary endpoints 5

1. Overall Survival in the HER2 IHC 3+/2+ population Time interval from the date of randomization to the date of death due to any cause.
2. Progression Free Survival by BICR in the HER2 IHC 3+/2+/1+ population. Time from randomization to time of objective radiographic disease progression as assessed by BICR based on RECIST v1.1 or death due to any cause.
3. Overall Survival in the HER2 IHC 3+/2+/1+ population Time interval from the date of randomization to the date of death due to any cause.
4. Progression Free Survival by the investigator in HER2 IHC 3+/2+ population Time from randomization to time of objective radiographic disease progression as assessed by the investigator based on RECIST v1.1 or death due to any cause.
5. Progression Free Survival by the investigator in HER2 IHC 3+/2+/1+ population Time from randomization to time of objective radiographic disease progression as assessed by the investigator based on RECIST v1.1 or death due to any cause.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Daiichi Sankyo Inc.

Sponsor organisation

Daiichi Sankyo Inc.

Address

211 Mount Airy Road

City

Basking Ridge

Postcode

07920-2311

Country

United States

Scientific contact point

Organisation

Daiichi Sankyo Europe GmbH

Contact name

Clinical Trial Office

Public contact point

Organisation

Daiichi Sankyo Europe GmbH

Contact name

Clinical Trial Office

Third parties 16

Locations

14 EU/EEA countries · 106 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 332 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

12 submissions — initial application plus substantial / non-substantial modifications