M9466 Alone or in Combination in Advanced Solid Tumors (DDriver 501)

NCT ID: NCT06421935

Last Updated: 2025-12-19

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 141 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-07
• Study Completion Date: 2027-02-22

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic profile of M9466 with and without tuvusertib or an ARPi and early signs of clinical activity of M9466 with tuvusertib in participants with advanced solid tumors. Study details include: Study/Treatment Duration: Participants will be treated until disease progression, death, discontinuation, or End of Study. Visit Frequency: Every week in the first 2 cycles, followed by every 3 weeks in the subsequent cycles. An End of Treatment Visit and Safety Follow-up/Discontinuation Visit are scheduled after the treatment period.

Conditions

Advanced Solid Tumor

Keywords

PARP inhibitor; castration-resistant Prostate cancer; ovarian cancer; Abiraterone Acetate

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

M9466 plus Tuvusertib

Group Type: EXPERIMENTAL

M9466

Intervention Type: DRUG

Participants will be administered M9466 orally.

Tuvusertib

Intervention Type: DRUG

Participants will be administered Tuvusertib orally.

M9466 Monotherapy

Group Type: EXPERIMENTAL

M9466

Intervention Type: DRUG

Participants will be administered M9466 orally.

M9466 with AA-P(abiraterone acetate and prednisone or prednisolone)

Group Type: EXPERIMENTAL

M9466

Intervention Type: DRUG

Participants will be administered M9466 orally.

Abiraterone acetate

Intervention Type: DRUG

Participants will be administered with Abiraterone acetate orally.

Prednisone/Prednisolone

Intervention Type: DRUG

Participants will be administered with prednisone/prednisolone orally.

Interventions

M9466

Participants will be administered M9466 orally.

Intervention Type: DRUG

Tuvusertib

Participants will be administered Tuvusertib orally.

Intervention Type: DRUG

Abiraterone acetate

Participants will be administered with Abiraterone acetate orally.

Intervention Type: DRUG

Prednisone/Prednisolone

Participants will be administered with prednisone/prednisolone orally.

Intervention Type: DRUG

Other Intervention Names

HRS-1167; Substance code MSC2584415A; also known as M1774, VXc-400, or VR 1363004; Abiraterone

Eligibility Criteria

Inclusion Criteria

• Module 1 Part A and Module 2 Part A1: Locally advanced or metastatic disease that is refractory to standard therapy or for which no standard therapy is judged appropriate by the Investigator
• Module 1 Part A2: Histologically or pathologically confirmed advanced or metastatic CRPC or EOC
• Eastern Cooperative Oncology Group Performance Status less than or equal to (<=) 1
• Life expectancy of more than 6 months
• Have adequate hematologic function
• Participants who received chemotherapy, extensive radiotherapy, biological therapy (e.g. antibodies) or investigational agents will have a washout period of 4 weeks (6 weeks for nitrosourea, mitomycin-C) or 5 half-lives whichever is shorter, prior to starting study intervention with M9466 (± tuvusertib)
• Module 3 Part A1:

• Histologically or pathologically confirmed diagnosis of prostate cancer
• Metastatic disease documented by positive bone scan or metastatic lesions on CT or MRI
• Participants with Metastatic Castration-Resistant Prostate Cancer (mCRPC) or metastatic hormone-sensitive prostate cancer (mHSPC) are allowed. For mCRPC, serum testosterone levels ≤ 50 /dL (≤ 1.75 nmol/L).
• Ongoing ADT with a GnRH agonist or antagonist for participants who have not undergone bilateral orchiectomy must be initiated before first dose and must continue throughout the study.
• Candidate for treatment with ·abiraterone acetate.
• Prior anticancer therapy allowed for mHSPC or mCRPC

Exclusion Criteria

• Persistence of Adverse Events related to any prior treatments that have not recovered to Grade less than 1 by NCI Common Terminology Criteria for Adverse Events- v5.0 unless AEs are clinically nonsignificant and/or stable on supportive therapy in the opinion of the Investigator (e.g. neuropathy or alopecia)
• Participant has a history of additional malignancy within 5 years before the date of enrollment other than disease under study (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, benign prostate neoplasm/hypertropia, or malignancy that in the opinion of the Investigator, with concurrence of the Sponsor's Medical Monitor, is considered cured with minimal risk of recurrence within 3 years)
• Participants with known brain metastases, except if clinically controlled, which is defined as individuals with Central Nervous System (CNS) tumors that have been treated, are asymptomatic and who have discontinued steroids (for the treatment of CNS tumors) for more than 28 days
• Serious Gastrointestinal bleeding within 3 months, refractory nausea and vomiting, uncontrolled diarrhea, known malabsorption, significant small bowel resection or gastric bypass surgery, use of feeding tubes, other chronic gastrointestinal disease (including exocrine pancreatic insufficiency requiring pancreatic enzyme replacement therapy), and/or other situations that may preclude adequate absorption of oral medications
• Cerebrovascular accident or stroke
• Module 3 only:

• Current evidence of any of the following:

1. Any medical condition that would make prednisone (or equivalent) use contraindicated.

2. Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone (or equivalent) once daily.

• History of uncontrolled pituitary or adrenal dysfunction
• Hypokalemia

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: collaborator

EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

EMD Serono Research & Development Institute, Inc.

Locations

NEXT Oncology - PARENT

New York, New York, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Cancer Research SA

Adelaide, , Australia

GenesisCare North Shore (Oncology)

St Leonards, , Australia

Harasanshin Hospital

Fukuoka, , Japan

National Cancer Center Hospital East - Dept of Experimental Therapeutics

Kashiwa-shi, , Japan

Cancer Institute Hospital of JFCR

Kōtoku, , Japan

NHO Kumamoto Medical Center - Dept of Urology

Kumamoto, , Japan

Seoul National University Bundang Hospital

Seongnam, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital, Yonsei University Health System - Division of Infectious Diseases

Seoul, , South Korea

Hospital HM Nou Delfos - START Barcelona

Barcelona, , Spain

Hospital Universitari Vall d'Hebron - Oncology Dept.

Barcelona, , Spain

ICO l'Hospitalet - Hospital Duran i Reynals - Servicio de Oncologia

Barcelona, , Spain

Centro Integral Oncologico Clara Campal - Unidad de Fase I-Oncologica

Madrid, , Spain

Hospital Universitario 12 de Octubre - Servicio de Oncologia

Madrid, , Spain

Hospital Universitario Fundacion Jimenez Diaz - START Madrid FJD - Oncology Phase I

Madrid, , Spain

NEXT Madrid - Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, , Spain

Countries

Germany; United States; Australia; Japan; South Korea; Spain

Related Links

https://clinicaltrials.emdgroup.com/en

Trial Awareness and Transparency website

https://medical.emdserono.com/en_US/home.html

US Medical Information website, Medical Resources

Other Identifiers

2024-513492-41-00

Identifier Type: OTHER

Identifier Source: secondary_id

MS202659_0001

Identifier Type: -

Identifier Source: org_study_id