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An Open Label, Multicenter, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of the PARP1 Inhibitor M9466 Alone or in Combination in Participants With Advanced Solid Tumors

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

Ishii Kyoko

Merck Biopharma Co., Ltd.

1-3-1 Azabudai, Minato-ku, Tokyo

MBJ_clinicaltrial_information@merckgroup.com

Ishii Kyoko

Merck Biopharma Co., Ltd.

1-3-1 Azabudai, Minato-ku, Tokyo

+81-3-4316-8010

MBJ_clinicaltrial_information@merckgroup.com

Not Recruiting

Aug. 06, 2024

Interventional

randomized controlled trial

open(masking not used)

uncontrolled control

parallel assignment

treatment purpose

- Module 1 Part A1 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 mCRPC or 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
- Other protocol defined inclusion criteria could apply

- 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 malignancy within 5 years before the date of enrollment (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:
a. Any medical condition that would make prednisone (or equivalent) use contraindicated.
b. 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
- Other protocol defined exclusion criteria could apply

Both

Advanced Solid Tumors

Drug: M9466
Participants will be administered M9466 orally.
Drug: Tuvusertib
Participants will be administered Tuvusertib orally.
Drug: Abiraterone acetate
Participants will be administered with Abiraterone acetate orally.
Drug: Prednisone/Prednisolone
Participants will be administered with Prednisone/Prednisolone orally.

- Module 1 Part A1 and Part A2: Number of Participants With Treatment-Emergent Adverse Events (TEAE), and Treatment-related AEs
- Module 1 Part A1 and Part A2: Number of Participants with Dose Limiting Toxicity (DLT)-like events
- Module 2 Part A1: Pharmacokinetic (PK) Plasma Concentrations of M9466
- Module 2 Part A2: Number of Participants With Treatment-Emergent Adverse Events (TEAE), and Treatment-related AEs
- Module 3 Part A1: Number of Participants With Treatment-Emergent Adverse Events (TEAE), and Treatment-related AEs
- Module 3 Part A1: Number of Participants with Dose Limiting Toxicity (DLT)-like events

July. 17, 2024

No

USA/Korea/Spain/UK/Australia