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

Clinicaltrials.gov ID: NCT06421935
db-list-check Status RECRUITING
b-loader Phase PHASE1
b-people Age ≥ 18 Years
b-bullseye-arrow Enrollments 96

Conditions

Advanced Solid Tumor

Drugs

M9466, Tuvusertib, Abiraterone acetate, Prednisone/Prednisolone

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.

Locations

2 locations Found with status Recruiting

Status

  • RECRUITING

Contact Person

Study Director

  • Medical Responsible

Status

  • RECRUITING

Contact Person

Study Director

  • Medical Responsible

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:

    M9466

    Description:

    Participants will be administered M9466 orally.
  • DRUG:

    Tuvusertib

    Description:

    Participants will be administered Tuvusertib orally.

M9466 Monotherapy

  • DRUG:

    M9466

    Description:

    Participants will be administered M9466 orally.

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

  • DRUG:

    Abiraterone acetate

    Description:

    Participants will be administered with Abiraterone acetate orally.
  • DRUG:

    Prednisone/Prednisolone

    Description:

    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

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: 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: Day 1, Day 8 and Day 15

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)

Secondary Outcome Measures

Module 1 Part A1: Pharmacokinetic (PK) Plasma Concentrations of M9466 and Tuvusertib

Time Frame: Day 1, Day 8 and Day 15

Module 1 Part A1: Objective Response (OR) According to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 as Assessed by Investigator

Time Frame: Time from first treatment to planned assessment at 12 months

Module 1 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: Number of Participants with Abnormalities in Digital Electrocardiogram (ECG) Measures

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: Pharmacokinetic (PK) Plasma Concentrations of M9466 and Tuvusertib

Time Frame: Day 1, Day 8 and Day 15

Module 2 Part A1: Relative Changes in Pharmacodynamic Markers In Paired Tumor Biopsies

Time Frame: Day 1, Day 8 and Day 15

Module 3 Part A1: Pharmacokinetic (PK) Plasma Concentrations of M9466 M9466 when administered in combination with AA-P

Time Frame: Day 1, Day 8 and Day 15

Timeline

  • Last Updated
    March 13, 2025
  • Start Date
    May 20, 2024
  • Today
    May 11, 2025
  • Completion Date ( Estimated )
    March 26, 2026

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