A Phase 1b/2 Open-label, Multicenter Study to Evaluate the Safety and Efficacy of Raludotatug Deruxtecan With or Without Other Anticancer Investigational Agents in Participants with High-grade Serous Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Who Have Relapsed After Prior Platinum-based Chemotherapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 May 2025 → ongoing

Decision date (initial)

2025-04-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC · Daiichi Sankyo

External identifiers

EU CT number

2024-514674-47-00

WHO UTN

U1111-1308-2821

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Pharmacokinetic, Safety, Diagnosis

1. Cohort A-1 Arm 1: To evaluate the safety and tolerability of raludotatug deruxtecan (R-DXd) administered in combination with carboplatin AUC 5 mg/ml • min in participants with PSROC
2. Cohort A-1 Arm 2: To evaluate the safety and tolerability of R-DXd administered in combination with paclitaxel in participants with PSROC
3. Cohort A-1 Arm 3: To evaluate the safety and tolerability of R-DXd administered in combination with carboplatin AUC 4 mg/ml • min in participants with PSROC
4. Cohort B-1: To evaluate the safety and tolerability of R-DXd administered in combination with bevacizumab in participants with PRROC
5. Cohort C-1: To evaluate the safety and tolerability of R-DXd administered in combination with pembrolizumab in participants with PSROC who progressed during prior treatment with PARPi in the first-line setting
6. Cohort B-2: To evaluate the ORR per RECIST 1.1 as assessed by BICR of R-DXd in combination with bevacizumab in participants with PRROC
7. Cohort D: To evaluate the ORR per RECIST 1.1 as assessed by BICR of R-DXd with or without bevacizumab in participants with PSROC who progressed during prior treatment with PARPi in the first-line setting

Secondary objectives 8

1. Cohort A-1 Arm 2: To evaluate ORR per RECIST 1.1 as assessed by BICR for R-DXd in combination with paclitaxel in participants with PSROC
2. Cohort A-1 Arm 3: To evaluate ORR per RECIST 1.1 as assessed by BICR for R-DXd in combination with carboplatin AUC 4 mg/mL • min in participants with PSROC
3. Cohort B-1: To evaluate ORR per RECIST 1.1 as assessed by BICR for R-DXd in combination with bevacizumab in participants with PRROC
4. Cohort C-1: To evaluate ORR per RECIST 1.1 as assessed by BICR for R-DXd in combination with pembrolizumab in participants with PSROC who progressed during prior treatment with PARPi in the first-line setting
5. Cohort B-2: To evaluate DOR and PFS per RECIST 1.1 as assessed by BICR, and OS, of RDXd in combination with bevacizumab in participants with PRROC
6. Cohort D: To evaluate DOR and PFS per RECIST 1.1 as assessed by BICR, and OS, of R-DXd with or without bevacizumab in participants with PSROC who progressed during prior treatment with PARPi in the first-line setting
7. Cohort B-2: To evaluate the safety and tolerability of R-DXd in combination with bevacizumab in participants with PRROC
8. Cohort D: To evaluate the safety and tolerability of R-DXd with or without bevacizumab in participants with PSROC who progressed during prior treatment with PARPi in the first-line setting

Conditions and MedDRA coding

High-grade Serous Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Who Have Relapsed After Prior Platinum-based Chemotherapy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Has pathologically documented diagnosis of high-grade serous epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer
2. Has measurable disease per Response Evaluation Criteria In Solid Tumors 1.1
3. Participants in Cohort A-1 Arm 2 and Arm 3: Has relapsed disease after 1 to 3 prior lines of therapy and radiographic evidence of disease progression ≥6 months (≥180 days) after the last dose of platinum-based therapy (ie, platinum-sensitive disease).
4. Participants in Cohort B-1 and Cohort B-2: Has relapsed disease after 1 to 3 prior lines of therapy and radiographic evidence of disease progression <6 months (<180 days) after the last dose of platinum-based therapy (ie, platinum-resistant disease).
5. Participants in Cohort B-1 and Cohort B-2: Is a candidate for bevacizumab treatment
6. Has provided tumor tissue from a core or excisional biopsy of a tumor lesion not previously irradiated
7. Has an Eastern Cooperative Oncology Group performance status of 0 to 1 assessed within 7 days before allocation
8. Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on anti-retroviral therapy
9. Participants who are hepatitis B surface antigen positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to allocation
10. Participants with a history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
11. Participants in Cohort C-1 and Cohort D: Has relapsed disease after 1 prior line of therapy, radiographic evidence of disease progression ≥6 months (≥180 days) after the last dose of platinum-based therapy (ie, platinum-sensitive disease) and progressed during prior treatment with PARPi in the first-line setting.

Exclusion criteria 12

1. Has any of the following within 6 months before allocation: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event
2. Has uncontrolled or significant cardiovascular disease
3. Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder, and any autoimmune, connective tissue, or inflammatory disorders with potential pulmonary involvement, or prior pneumonectomy
4. Has ≥Grade 2 peripheral neuropathy
5. Has received prior systemic anticancer therapy
6. Has received prior radiotherapy within 2 weeks of the start of study intervention, or has radiation-related toxicities, requiring corticosteroids
7. Receives chronic steroid treatment
8. Has known additional malignancy that is progressing or has required active treatment within the past 3 years
9. Has known active CNS metastases and/or carcinomatous meningitis
10. Has history of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD
11. Has active infection requiring systemic therapy
12. HIV-infected participants with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Part 1: Number of Participants Who Experience a Dose-limiting Toxicity (DLT) Per Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE v5.0)
2. Part 1: Number of Participants with One or More Adverse Events (AEs)
3. Part 1: Number of Participants who Discontinue Study Intervention Due to an AE
4. Part 2: Objective Response Rate (ORR)

Secondary endpoints 6

1. Part 1: Objective Response Rate (ORR)
2. Part 2: Duration of Response (DOR)
3. Part 2: Progression-free Survival (PFS)
4. Part 2: Overall Survival (OS)
5. Part 2: Number of Participants with One or More AEs
6. Part 2: Number of Participants who Discontinue Study Intervention due to an AE

Investigational products

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

Test 9

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

128 Sidney Street

City

Cambridge

Postcode

02139-4239

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Carmen González

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Carmen González

Third parties 4

Locations

1 EU/EEA country · 8 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 10 files

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

Application history

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