Clinical trial NCT06719973: Phase 1 Study of M9466 Combined With Carboplatin and Platinum-based Anticancer Therapy (DDRiver 521)
Official title: An Open Label, Multicenter, Phase 1 Study of the PARP1 Inhibitor M9466 in Combination With Carboplatin and Platinum-based Anticancer Therapy (DDRiver 521)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: PARP inhibitor
DNA damage repair inhibitor
etoposide
atezolizumab
SCLC
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2024-12-06
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Module 1 and Module 2: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Treatment Related TEAEs
timeFrame: Time from signing Informed Consent Form (ICF) up to 30 days after end of study intervention (approximately assessed up to 24 months)
measure: Module 1 and Module 2: Number of Participants with Dose-limiting Toxicity (DLT)
timeFrame: Day 1 up to Day 21 of Cycle 1 (each cycle is of 21 days)
Secondary outcomes:
measure: Module 1 and Module 2: Pharmacokinetic (PK) Plasma Concentration of M9466
timeFrame: 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)
measure: 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
timeFrame: Time from first treatment of study intervention up to planned assessment at 24 months
measure: 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
timeFrame: Time from first treatment of study intervention up to planned assessment at 24 months
measure: 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
timeFrame: Time from first treatment of study intervention up to planned assessment at 24 months
Other outcomes:
Locations:
Study officials:
affiliation: EMD Serono Research & Development Institute, Inc.
name: Medical Responsible
role: STUDY_DIRECTOR
References: