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

Merck KGaA (EMD Serono)

Status and phase: Withdrawn; Phase 1

Conditions: Advanced Solid Tumors

Treatments: Drug: Atezolizumab; Drug: Etoposide; Drug: M9466; Drug: M9446; Drug: Carboplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT06719973

MS202650_0009

2024-514921-45-00 (Other Identifier)

Details and patient eligibility

About

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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

0 participants in 3 patient groups

Module 1 (Dose Finding): M9466 + Carboplatin

Experimental group

Treatment:

Drug: Carboplatin

Drug: Carboplatin

Drug: M9466

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

Experimental group

Treatment:

Drug: Carboplatin

Drug: M9446

Drug: Carboplatin

Drug: M9446

Drug: Etoposide

Drug: Atezolizumab

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

Experimental group

Treatment:

Drug: Carboplatin

Drug: M9446

Drug: Carboplatin

Drug: M9446

Drug: Etoposide

Drug: Atezolizumab