Non-Small Cell Lung Cancer
Conditions
Keywords
Ataxia telangiectasia mutated and Rad3-related protein kinase (ATR) inhibitor, Tuvusertib (M1774), Non squamous Non small cell lung cancer, Cemiplimab
Brief summary
This is an Open-label, multicenter clinical study conducted in two Phases to establish the efficacy, safety, tolerability, and pharmacokinetics of the ataxia telangiectasia mutated and Rad3-related protein kinase (ATR) inhibitor Tuvusertib in Combination with Cemiplimab in Participants with Non-Squamous Non-Small Cell Lung Cancer (nsqNSCLC) that has Progressed on Prior Anti-PD-(L)1 and Platinum-based Therapies..
Interventions
DRUGM1774
In Phase 1b, M1774 will be administered as dosing regimen 1 or dosing regimen 2 until disease progression, death discontinuation criteria or any other reason. The selected dosing regimen of M1774 will be administered in all arms of Phase 2a.
DRUGCemiplimab
Cemiplimab will be administered as an intravenous infusion every 3 weeks in all arms of Phase 1b and Phase 2a until disease progression, death discontinuation criteria or any other reason.
Sponsors
EMD Serono Research & Development Institute, Inc.
Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants who are diagnosed with nsqNSCLC histologically or cytologically confirmed * Participants with Radiologically confirmed/documented disease progression during or after the following systemic therapies (all required): * At most, 1 line of anti-PD-(L)1 therapy for locally advanced or metastatic disease. Rechallenge with the same anti-PD-(L)1 for disease considered sensitive to anti-PD-(L)1 therapy (e.g. after a treatment break) is considered 1 line * Platinum-based therapy for locally advanced or metastatic disease, given in combination or sequentially with anti-PD-(L)1 therapy. Participants who received adjuvant platinum-based therapy meet this criterion if disease progression occurred within 6 months from the last dose that the participant received that therapy. No additional cytotoxic therapies after progression on platinum-based therapy are allowed * Prior best overall response of stable disease or better with anti-PD-(L)1 therapy * Disease progression must have occurred while the participant has been receiving anti-PD-(L)1 therapy or within 16 weeks of the last dose of anti-PD-(L)1 therapy * Participants with Measurable disease per RECIST v1.1 * Participants with Eastern Cooperative Oncology Group (ECOG) PS 0 or 1 * Adequate hematological, hepatic, and renal function as defined in the protocol. * Phase 2a part only: central liquid biopsy analysis of tumor molecular alterations with an assay with appropriate regulatory status * Other protocol defined inclusion criteria could apply
Exclusion criteria
* Participants with tumors harboring actionable epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic aberrations. Participants with tumors with other actionable aberrations are eligible and allowed to have received up to 1 line of available targeted therapy * Participants with history of additional 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, or malignancy that in the opinion of the Investigator, with concurrence of the Sponsor's Medical Monitor, is considered cured with minimal risk of recurrence within 3 years * Participants with known brain metastases, unless clinically stable * Participant with history of (noninfectious) pneumonitis that required systemic corticosteroids or current pneumonitis/interstitial lung disease * Other protocol defined
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 1b/Phase 2a: Confirmed Overall response (OR) According to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 As assessed by Investigator | Time from randomization to final assessment or until progression disease, death, discontinuation criteria approximately up to 3 years and 2 months |
| Phase 1b: Number of Participants With Adverse Events (AEs) and Treatment-related AEs | Time from randomization to final assessment at end of safety follow-up visit approximately up to 3 years and 2 months |
Secondary
| Measure | Time frame |
|---|---|
| Phase 1b/Phase 2a: Duration of Response (DoR) According to RECIST 1.1 as Assessed by the Investigator | Time from randomization to final assessment or until progression disease, death, discontinuation criteria approximately up to 3 years and 2 months |
| Phase 1b/Phase 2a: Progression Free Survival (PFS) According to RECIST 1.1 as Assessed by the Investigator | Time from randomization to final assessment or until progression disease, death, discontinuation criteria approximately up to 3 years and 2 months |
| Phase 1b/Phase 2a: Overall survival (OS) | Time from randomization to final assessment or until progression disease, death, discontinuation criteria approximately up to 3 years and 2 months |
| Phase 2a: Number of Participants With AEs and Treatment-related AEs | Time from randomization to final assessment at end of safety follow-up visit (approximately up to 3 years and 2 months) |
Countries
Belgium, France, Germany, Italy, Japan, South Korea, Spain, United States
Contacts
STUDY_DIRECTORMedical Responsible
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Outcome results
None listed