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

An Open Label, Multicenter, Phase 1 Study of the PARP1 Inhibitor M9466 in Combination With Carboplatin and Platinum-based Anticancer Therapy (DDRiver 521)

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.

Study Overview

• Status: Withdrawn
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: Carboplatin; Drug: M9466; Drug: Carboplatin; Drug: Etoposide; Drug: Atezolizumab; Drug: M9446; Drug: M9446

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Chuo-ku, Japan, 104-0045
    • National Cancer Center Hospital - Dept of Respiratory Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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
• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• 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
• Other protocol defined exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Module 1 (Dose Finding): M9466 + Carboplatin	Drug: Carboplatin; Carboplatin will be administered intravenously as per standard of care.; Drug: M9466; 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.; Other Names: HRS-1167; Drug: Carboplatin; Carboplatin will be administered intravenously on Day 1 of each 21-day cycle.
Experimental: Module 2 Part A (Dose Reassessment): M9466 + Carboplatin + Etoposide + Atezolizumab	Drug: Carboplatin; Carboplatin will be administered intravenously as per standard of care.; Drug: Carboplatin; Carboplatin will be administered intravenously on Day 1 of each 21-day cycle.; Drug: Etoposide; Etoposide will be administered intravenously as per standard of care.; Drug: Atezolizumab; Atezolizumab will be administered intravenously as per standard of care.; Drug: M9446; M9446 dose will be further investigated in Module 2 Part A of the study.; Other Names: HRS-1167; Drug: M9446; M9446 recommended Dose for Expansion (RDE) will be further investigated in Module 2 Part B of the study.; Other Names: HRS-1167
Experimental: Module 2 Part B (Dose Expansion): M9466 + Carboplatin + Etoposide + Atezolizumab	Drug: Carboplatin; Carboplatin will be administered intravenously as per standard of care.; Drug: Carboplatin; Carboplatin will be administered intravenously on Day 1 of each 21-day cycle.; Drug: Etoposide; Etoposide will be administered intravenously as per standard of care.; Drug: Atezolizumab; Atezolizumab will be administered intravenously as per standard of care.; Drug: M9446; M9446 dose will be further investigated in Module 2 Part A of the study.; Other Names: HRS-1167; Drug: M9446; M9446 recommended Dose for Expansion (RDE) will be further investigated in Module 2 Part B of the study.; Other Names: HRS-1167

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: EMD Serono Research & Development Institute, Inc.
• Collaborators: Merck KGaA, Darmstadt, Germany
• Investigators: Study Director: Medical Responsible, EMD Serono Research & Development Institute, Inc.

Publications and helpful links

Helpful Links

• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2025
• Primary Completion (Actual): May 14, 2025
• Study Completion (Actual): May 14, 2025

Study Registration Dates

• First Submitted: December 2, 2024
• First Submitted That Met QC Criteria: December 2, 2024
• First Posted (Actual): December 6, 2024

Study Record Updates

• Last Update Posted (Actual): June 17, 2025
• Last Update Submitted That Met QC Criteria: June 13, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: PARP inhibitor; atezolizumab; etoposide; SCLC; DNA damage repair inhibitor
• Additional Relevant MeSH Terms: Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Atezolizumab; Etoposide; Carboplatin
• Other Study ID Numbers: MS202650_0009; 2024-514921-45-00 (Other Identifier: EU CTR)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No