Advanced Solid Tumors
Conditions
Keywords
PARP inhibitor, DNA damage repair inhibitor, etoposide, atezolizumab, SCLC
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.
Interventions
DRUGM9466
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.
DRUGCarboplatin
Carboplatin will be administered intravenously on Day 1 of each 21-day cycle.
DRUGEtoposide
Etoposide will be administered intravenously as per standard of care.
DRUGAtezolizumab
Atezolizumab will be administered intravenously as per standard of care.
DRUGM9446
M9446 dose will be further investigated in Module 2 Part A of the study.
Sponsors
Merck KGaA, Darmstadt, Germany
EMD Serono Research & Development Institute, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| 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 |
Outcome results
None listed