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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Participants will be administered M9466 orally.
Participants will be administered Tuvusertib orally.
Participants will be administered with Abiraterone acetate orally.
Participants will be administered with prednisone/prednisolone orally.
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
...and 10 more locations
Module 1 Part A1 and Part A2: Number of Participants With Treatment-Emergent Adverse Events (TEAE), and Treatment-related AEs (TRAEs)
Time frame: 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
Time frame: 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
Time frame: 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 frame: 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 frame: 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
Time frame: Day 1 up to Day 21 of Cycle 1(each cycle is of 21 days)
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
Time frame: 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 frame: 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 frame: 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 frame: 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
Time frame: Day 1, Day 8 and Day 15
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