M9466: Participants will be administered M9466 orally.
Tuvusertib: Participants will be administered Tuvusertib orally.
Abiraterone acetate: Participants will be administered with Abiraterone acetate orally.
Prednisone/Prednisolone: Participants will be administered with prednisone/prednisolone orally.
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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
* Other protocol defined inclusion criteria could apply
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
* Other protocol defined exclusion criteria could apply
Primary outcome measure(s)
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)
Trial sites (20)
Facility
City
Region
Status
NEXT Oncology - PARENT
New York
New York
The University of Texas MD Anderson Cancer Center
Houston
Texas
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
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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