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

Phase 1

Not yet recruiting

Interventions: Drug: M9466
Drug: Etoposide
Drug: Carboplatin
Drug: Atezolizumab
Drug: M9446

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 inv...

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Module 1 (Dose Finding): M9466 + Carboplatin	M9466	-
Module 1 (Dose Finding): M9466 + Carboplatin	Carboplatin	-
Module 2 Part A (Dose Reassessment): M9466 + Carboplatin + Etoposide + Atezolizumab	Etoposide	-
Module 2 Part A (Dose Reassessment): M9466 + Carboplatin + Etoposide + Atezolizumab	Atezolizumab	-
Module 2 Part A (Dose Reassessment): M9466 + Carboplatin + Etoposide + Atezolizumab	M9446	-
Module 2 Part A (Dose Reassessment): M9466 + Carboplatin + Etoposide + Atezolizumab	Carboplatin	-
Module 2 Part B (Dose Expansion): M9466 + Carboplatin + Etoposide + Atezolizumab	Etoposide	-
Module 2 Part B (Dose Expansion): M9466 + Carboplatin + Etoposide + Atezolizumab	Atezolizumab	-
Module 2 Part B (Dose Expansion): M9466 + Carboplatin + Etoposide + Atezolizumab	M9446	-
Module 2 Part B (Dose Expansion): M9466 + Carboplatin + Etoposide + Atezolizumab	Carboplatin	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Locations (2): Please Contact U.S. Medical Information
🇺🇸
Billerica, Massachusetts, United States
Please Contact the Communication Center
🇩🇪
Darmstadt, Germany