Phase 1 Study of M9466 Combined With Carboplatin and Platinum-based Anticancer Therapy (DDRiver 521)

NCT06719973 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: MS202650_00092024-514921-45-00
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamic, and preliminary clinical activity of M9466 in combinations with carboplatin in advanced or metastatic refractory solid tumor and with the standard of care (carboplatin, etoposide, and atezolizumab) in treatment-naïve ES-SCLC. The results will support any investigation of carboplatin-based combination anticancer treatments with M9466 as well as the selection of a RP2D of M9466 in combination with carboplatin, etoposide, and atezolizumab for a subsequent ES-SCLC study.

Conditions

Advanced Solid Tumors

Keywords

PARP inhibitor; DNA damage repair inhibitor; etoposide; atezolizumab; SCLC

Outcome Measures

Primary Outcomes (2)

• Module 1 and Module 2: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Treatment Related TEAEs

  Time from signing Informed Consent Form (ICF) up to 30 days after end of study intervention (approximately assessed up to 24 months)

• Module 1 and Module 2: Number of Participants with Dose-limiting Toxicity (DLT)

  Day 1 up to Day 21 of Cycle 1 (each cycle is of 21 days)

Secondary Outcomes (4)

• Module 1 and Module 2: Pharmacokinetic (PK) Plasma Concentration of M9466

  Pre-dose up to 6 hours post-dose on Cycle 1 Day 1; Pre-dose on Cycle 1 Day 4 and Cycle 1 Day 8 (each cycle is of 21 days)

• Module 1 and Module 2: Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) Assessed by Investigator

  Time from first treatment of study intervention up to planned assessment at 24 months

• Module 1 and Module 2: Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as Assessed by the Investigator

  Time from first treatment of study intervention up to planned assessment at 24 months

• Module 1 and Module 2: Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as Assessed by Investigator

  Time from first treatment of study intervention up to planned assessment at 24 months

Study Arms (3)

Module 1 (Dose Finding): M9466 + Carboplatin

EXPERIMENTAL

Drug: M9466; Drug: Carboplatin

Module 2 Part A (Dose Reassessment): M9466 + Carboplatin + Etoposide + Atezolizumab

EXPERIMENTAL

Drug: Etoposide; Drug: Atezolizumab; Drug: M9446; Drug: Carboplatin

Module 2 Part B (Dose Expansion): M9466 + Carboplatin + Etoposide + Atezolizumab

EXPERIMENTAL

Drug: Etoposide; Drug: Atezolizumab; Drug: M9446; Drug: Carboplatin

Interventions

M9466 DRUG

Participants will receive an escalating doses of M9466 orally in 21-day cycles until disease progression, intolerable toxicity, death, withdrawal of study or study consent, lost to follow-up, or end of study.

Also known as: HRS-1167

Module 1 (Dose Finding): M9466 + Carboplatin

Carboplatin DRUG

Carboplatin will be administered intravenously on Day 1 of each 21-day cycle.

Module 1 (Dose Finding): M9466 + Carboplatin

Etoposide DRUG

Etoposide will be administered intravenously as per standard of care.

Module 2 Part A (Dose Reassessment): M9466 + Carboplatin + Etoposide + Atezolizumab; Module 2 Part B (Dose Expansion): M9466 + Carboplatin + Etoposide + Atezolizumab

Atezolizumab DRUG

Atezolizumab will be administered intravenously as per standard of care.

Module 2 Part A (Dose Reassessment): M9466 + Carboplatin + Etoposide + Atezolizumab; Module 2 Part B (Dose Expansion): M9466 + Carboplatin + Etoposide + Atezolizumab

M9446 DRUG

M9446 dose will be further investigated in Module 2 Part A of the study.

Also known as: HRS-1167

Module 2 Part A (Dose Reassessment): M9466 + Carboplatin + Etoposide + Atezolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Module 1: Locally advanced or metastatic solid tumors that are refractory to standard therapy or for which no standard therapy is judged appropriate by the Investigator (that is \[i.e.\] participants who have exhausted all standard of care options according to International Guidelines), which may convey clinical benefit from the combination treatment with M9466 and carboplatin and have not received more than 3 lines of prior anticancer therapy in the advanced/metastatic setting Module 2: Histologically or cytologically confirmed treatment-naïve, de novo, extensive stage small cell lung cancer (ES-SCLC), who have no history of systemic treatment for the disease. Participant must be considered suitable to receive carboplatin, etoposide, and atezolizumab as first-line treatment for ES-SCLC
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) less than or equal to (\<=) 1 (ECOG PS 2 eligible if considered related to SCLC tumor load in Module 2)
• Have adequate hematological, hepatic, and renal function as defined in the protocol

You may not qualify if:

• Module 1: Persistence of AEs related to any prior treatments that have not recovered to Grade \<= 1 by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 unless AEs are clinically non-significant and /or stable on supportive therapy in the opinion of the Investigator (for example \[e.g.\] neuropathy or alopecia)
• Module 2: Participant has a history of malignancy within 3 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, 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 CNS tumors that are asymptomatic and who do not require steroids for the treatment of CNS tumors
• Life expectancy of less than (\<) 3 months

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Related Links

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources

MeSH Terms

Interventions

Carboplatin; Etoposide; atezolizumab

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Medical Responsible

  EMD Serono Research & Development Institute, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2024
• First Posted: December 6, 2024
• Study Start: May 14, 2025
• Primary Completion: May 14, 2025
• Study Completion: May 14, 2025
• Last Updated: June 17, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share