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

Merck KGaA (EMD Serono)

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Non-Small Cell Lung Cancer

Treatments: Drug: Cemiplimab; Drug: M1774

Study type: Interventional

Funder types: Industry

Identifiers

NCT05882734

MS201924_0022

2022-502010-85-00 (Other Identifier)

Details and patient eligibility

About

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..

Enrollment: 61 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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61 participants in 5 patient groups

Dosing Regimen 1 (Phase 1b): M1774 + Cemiplimab

Experimental group

Treatment:

Drug: M1774

Drug: Cemiplimab

Dosing Regimen 2 (Phase 1b): M1774 + Cemiplimab

Experimental group

Treatment:

Drug: M1774

Drug: Cemiplimab

Stratum A (Phase 2a): Either Dosing Regimen 1 or 2 as finalized in Phase 1b

Experimental group

Treatment:

Drug: M1774

Drug: Cemiplimab

Stratum B (Phase 2a): Either Dosing Regimen 1 or 2 as finalized in Phase 1b

Experimental group

Treatment:

Drug: M1774

Drug: Cemiplimab

Stratum C (Phase 2a): Either Dosing Regimen 1 or 2 as finalized in Phase 1b

Experimental group

Treatment:

Drug: M1774

Drug: Cemiplimab