M9466 Alone or in Combination in Advanced Solid Tumors (DDriver 501)
Conditions
Advanced Solid TumorDrugs
M9466, Tuvusertib, Abiraterone acetate, Prednisone/PrednisoloneSummary
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.
Locations
2 locations Found with status Recruiting
Eligibility Criteria
Inclusion Criteria:
* 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
* 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 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:
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
Study Plan
M9466 plus Tuvusertib
DRUG:
M9466Description:
Participants will be administered M9466 orally.DRUG:
TuvusertibDescription:
Participants will be administered Tuvusertib orally.
M9466 Monotherapy
DRUG:
M9466Description:
Participants will be administered M9466 orally.
M9466 with AA-P(abiraterone acetate and prednisone or prednisolone)
DRUG:
Abiraterone acetateDescription:
Participants will be administered with Abiraterone acetate orally.DRUG:
Prednisone/PrednisoloneDescription:
Participants will be administered with prednisone/prednisolone orally.
Outcome Measures
Primary Outcome Measures
Module 1 Part A1: Number of Participants With Treatment-Emergent Adverse Events (TEAE), and Treatment-related AEs
Module 1 Part A1: Number of Participants with Dose Limiting Toxicity (DLT)-like events
Module 2 Part A1: Pharmacokinetic (PK) Plasma Concentrations of M9466
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
Secondary Outcome Measures
Module 1 Part A1: Pharmacokinetic (PK) Plasma Concentrations of M9466 and Tuvusertib
Module 1 Part A1: Objective Response (OR) According to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 as Assessed by Investigator
Module 1 Part A1: Effect of M9466 in combination with tuvusertib on QTc interval as determined by Digital ECGs
Module 2 Part A1: Number of Participants With Treatment-Emergent Adverse Events (TEAE), and Treatment-Related AEs
Module 2 Part A1: Number of Participants with Abnormalities in Digital Electrocardiogram (ECG) Measures
Module 2 Part A1: Pharmacokinetic (PK) Plasma Concentrations of M9466 and Tuvusertib
Module 2 Part A1: Relative Changes in Pharmacodynamic Markers In Paired Tumor Biopsies
Module 3 Part A1: Pharmacokinetic (PK) Plasma Concentrations of M9466 M9466 when administered in combination with AA-P
Timeline
Last Updated
March 13, 2025Start Date
May 20, 2024Today
May 11, 2025Completion Date ( Estimated )
March 26, 2026
Sponsors of this trial
Lead Sponsor
EMD Serono Research & Development Institute, Inc.Collaborating Sponsors
Merck KGaA, Darmstadt, Germany