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

NCT06421935 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: MS202659_00012024-513492-41-00
• Study Type: interventional
• Target: 141
• Locations: 5 countries
• Sites: 20

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

Outcome Measures

Primary Outcomes (6)

• Module 1 Part A1 and Part A2: Number of Participants With Treatment-Emergent Adverse Events (TEAE), and Treatment-related AEs (TRAEs)

  Time from first treatment up to 30 days after end of study intervention (approximately assessed up to 20 months)

• Module 1 Part A1 and Part A2: Number of Participants with Dose Limiting Toxicity (DLT)-like events

  Day 1 up to Day 21 of Cycle 1 (each cycle is of 21 days)

• Module 2 Part A1: Pharmacokinetic (PK) Plasma Concentrations of M9466

  Cycle 1 Day 1 (C1D1), C1D8 and C1D15

• Module 2 Part A2: Number of Participants With Treatment-Emergent Adverse Events (TEAE), and Treatment-related AEs (TRAEs)

  Time from first treatment up to 30 days after end of study intervention (approximately assessed up to 20 months)

• Module 3 Part A1: Number of Participants With Treatment-Emergent Adverse Events (TEAE), and Treatment-related AEs

  Time from first treatment up to 30 days after end of study intervention

• Module 3 Part A1: Number of Participants with Dose Limiting Toxicity (DLT)-like Events

  Day 1 up to Day 21 of Cycle 1(each cycle is of 21 days)

Secondary Outcomes (5)

• Module 1 Part A1 and Part A2, Module 2 Part A1 and A2 and Module 3 Part A1: Pharmacokinetic (PK) Plasma Concentrations of M9466 and Tuvusertib

  Module 1 Part A1: C1D1 and C1D5 or C1D6; Module 1 Part A2: C1D1, C1D2, C1D3 or C1D4 and C1D8; Module 2 Part A1: C1D1, C1D8 and C1D15; Module 2 Part A2: C1D1, C1D2 and C1D8, C1D22 and C2D1; Module 2 Part A1: C1D1 and C1D8

• Module 1 Part A1 and Part A2, Module 2 Part A2: Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (or PCWG3 for prostate cancer) as Assessed by Investigator

  Time from first treatment to planned assessment at 12 months

• Module 1 Part A1 and Part A2; Module 2 Part A1 : Effect of M9466 in combination with tuvusertib on QTc interval as determined by Digital ECGs

  Time from first treatment to planned assessment at 12 months

• Module 2 Part A1: Number of Participants With Treatment-Emergent Adverse Events (TEAE), and Treatment-Related AEs

  Time from first treatment up to 30 days after end of study intervention (approximately assessed up to 20 months)

• Module 2 Part A1 and Part A2: Relative Changes in Pharmacodynamics Markers in Paired Tumor Biopsies

  Day 1, Day 8 and Day 15

Study Arms (3)

M9466 plus Tuvusertib

EXPERIMENTAL

Drug: M9466; Drug: Tuvusertib

M9466 Monotherapy

EXPERIMENTAL

Drug: M9466

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

EXPERIMENTAL

Drug: M9466; Drug: Abiraterone acetate; Drug: Prednisone/Prednisolone

Interventions

M9466 DRUG

Participants will be administered M9466 orally.

Also known as: HRS-1167;

M9466 Monotherapy; M9466 plus Tuvusertib; M9466 with AA-P(abiraterone acetate and prednisone or prednisolone)

Tuvusertib DRUG

Participants will be administered Tuvusertib orally.

Also known as: Substance code MSC2584415A; also known as M1774, VXc-400, or VR 1363004

M9466 plus Tuvusertib

Abiraterone acetate DRUG

Participants will be administered with Abiraterone acetate orally.

Also known as: Abiraterone

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

Prednisone/Prednisolone DRUG

Participants will be administered with prednisone/prednisolone orally.

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (20)

NEXT Oncology - PARENT

New York, New York, 10065, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Cancer Research SA

Adelaide, Australia

Location

GenesisCare North Shore (Oncology)

St Leonards, Australia

Location

Harasanshin Hospital

Fukuoka, Japan

Location

National Cancer Center Hospital East - Dept of Experimental Therapeutics

Kashiwa-shi, Japan

Location

Cancer Institute Hospital of JFCR

Kōtoku, Japan

Location

NHO Kumamoto Medical Center - Dept of Urology

Kumamoto, Japan

Location

Seoul National University Bundang Hospital

Seongnam, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

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

Seoul, South Korea

Location

Hospital HM Nou Delfos - START Barcelona

Barcelona, Spain

Location

Hospital Universitari Vall d'Hebron - Oncology Dept.

Barcelona, Spain

Location

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

Barcelona, Spain

Location

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

Madrid, Spain

Location

Hospital Universitario 12 de Octubre - Servicio de Oncologia

Madrid, Spain

Location

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

Madrid, Spain

Location

NEXT Madrid - Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, Spain

Location

Related Links

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Abiraterone Acetate; abiraterone; Prednisone; Prednisolone

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Pregnadienetriols

Study Officials

• Medical Responsible

  EMD Serono Research & Development Institute, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2024
• First Posted: May 20, 2024
• Study Start: August 7, 2024
• Primary Completion (Estimated): February 22, 2027
• Study Completion (Estimated): February 22, 2027
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2); KR (5); US (2); ES (7); JP (4)