M1774 in Combination With Cemiplimab in Participants With Non-Squamous NSCLC (DDRiver NSCLC 322)

Sponsor

EMD Serono Research & Development Institute, Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05882734

Collaborator

Merck KGaA, Darmstadt, Germany (Industry)

180

Enrollment

Location

Arms

37.8

Anticipated Duration (Months)

4.8

Patients Per Site Per Month

Study Details

Study Description

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 M1774 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

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer	Drug: M1774 Drug: Cemiplimab	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

180 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open Label, Multicenter, Phase 1b/2a Study to Evaluate Efficacy, Safety, Tolerability, and Pharmacokinetics of the ATR Inhibitor M1774 in Combination With Cemiplimab in Participants With Non-Squamous Non-Small Cell Lung Cancer That Has Progressed on Prior Anti-PD-(L)1 and Platinum-based Therapies (DDRiver NSCLC 322)

Anticipated Study Start Date :

Jul 11, 2023

Anticipated Primary Completion Date :

Aug 25, 2026

Anticipated Study Completion Date :

Sep 3, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dosing Regimen 1 (Phase 1b): M1774 + Cemiplimab	Drug: M1774 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. Drug: Cemiplimab 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.
Experimental: Dosing Regimen 2 (Phase 1b): M1774 + Cemiplimab	Drug: M1774 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. Drug: Cemiplimab 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.
Experimental: Stratum A (Phase 2a): Either Dosing Regimen 1 or 2 as finalized in Phase 1b	Drug: M1774 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. Drug: Cemiplimab 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.
Experimental: Stratum B (Phase 2a): Either Dosing Regimen 1 or 2 as finalized in Phase 1b	Drug: M1774 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. Drug: Cemiplimab 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.
Experimental: Stratum C (Phase 2a): Either Dosing Regimen 1 or 2 as finalized in Phase 1b	Drug: M1774 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. Drug: Cemiplimab 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.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 exclusion criteria could apply