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

Merck KGaA (EMD Serono)

Status and phase: Active, not recruiting; Phase 1

Conditions: Advanced Solid Tumor

Treatments: Drug: Prednisone/Prednisolone; Drug: Abiraterone acetate; Drug: M9466; Drug: Tuvusertib

Study type: Interventional

Funder types: Industry

Identifiers

NCT06421935

MS202659_0001

2024-513492-41-00 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 141 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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141 participants in 3 patient groups

M9466 plus Tuvusertib

Experimental group

Treatment:

Drug: Tuvusertib

Drug: M9466

M9466 Monotherapy

Experimental group

Treatment:

Drug: M9466

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

Experimental group

Treatment:

Drug: Abiraterone acetate

Drug: M9466

Drug: Prednisone/Prednisolone