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

NCT05882734 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: MS201924_00222022-502010-85-00
• Study Type: interventional
• Target: 61
• Locations: 8 countries
• Sites: 54

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..

Conditions

Non-Small Cell Lung Cancer

Keywords

Ataxia telangiectasia mutated and Rad3-related protein kinase (ATR) inhibitor; Tuvusertib (M1774); Non squamous Non small cell lung cancer; Cemiplimab

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• 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)

Study Arms (5)

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

EXPERIMENTAL

Drug: M1774; Drug: Cemiplimab

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

EXPERIMENTAL

Drug: M1774; Drug: Cemiplimab

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

EXPERIMENTAL

Drug: M1774; Drug: Cemiplimab

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

EXPERIMENTAL

Drug: M1774; Drug: Cemiplimab

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

EXPERIMENTAL

Drug: M1774; Drug: Cemiplimab

Interventions

M1774 DRUG

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.

Also known as: Tuvusertib

Dosing Regimen 1 (Phase 1b): M1774 + Cemiplimab; Dosing Regimen 2 (Phase 1b): M1774 + Cemiplimab; Stratum A (Phase 2a): Either Dosing Regimen 1 or 2 as finalized in Phase 1b; Stratum B (Phase 2a): Either Dosing Regimen 1 or 2 as finalized in Phase 1b; Stratum C (Phase 2a): Either Dosing Regimen 1 or 2 as finalized in Phase 1b

Cemiplimab DRUG

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.

Dosing Regimen 1 (Phase 1b): M1774 + Cemiplimab; Dosing Regimen 2 (Phase 1b): M1774 + Cemiplimab; Stratum A (Phase 2a): Either Dosing Regimen 1 or 2 as finalized in Phase 1b; Stratum B (Phase 2a): Either Dosing Regimen 1 or 2 as finalized in Phase 1b; Stratum C (Phase 2a): Either Dosing Regimen 1 or 2 as finalized in Phase 1b

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (54)

UCLA Hematology and Oncology - Santa Monica

Santa Monica, California, 90404, United States

Location

UPMC Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Tennessee Cancer Specialists - Biomedical Research

Knoxville, Tennessee, 37909, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Millennium Research & Clinical Development

Houston, Texas, 77090, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Institut Jules Bordet - Department of Institut Jules Bordet'

Anderlecht, Belgium

Location

UZA - Oncology

Edegem, Belgium

Location

Jessa Ziekenhuis Hospital

Hasselt, Belgium

Location

Universitair Ziekenhuis Brussel - UZB

Jette, Belgium

Location

UZ Leuven

Leuven, Belgium

Location

CHU de Liège - PARENT

Liège, Belgium

Location

CHU Angers - Hôpital Larrey - Service de Pneumologie

Angers, France

Location

Centre Hospitalier Intercommunal de Créteil - Service de Pneumologie

Créteil, France

Location

CHU Limoges - Hôpital Dupuytren - Unite d'Oncologie Thoracique et Cutanée

Limoges, France

Location

Hôpital de la Timone - CPCEM CIC - Bat F 1er étage

Marseille, France

Location

Hopital Arnaud de Villeneuve - Service de Pneumologie-Addictologie

Montpellier, France

Location

Groupe Hospitalier Sud - Hôpital Haut-Lévêque - Unité d'Explorations Fonctionnelles Respiratoires

Pessac, France

Location

ICO - Site René Gauducheau - Service d'Oncologie medicale

Saint-Herblain, France

Location

Universitaetsklinikum Giessen und Marburg GmbH - Medizinische Klinik und Poliklinik III

Giessen, Germany

Location

Universitaetsklinikum Leipzig AoeR - Med. Klinik u. Poliklinik I - Abt. Pneumologie

Leipzig, Germany

Location

Sana Klinikum Offenbach GmbH - Medizinische Klinik IV

Offenbach, Germany

Location

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS - U.O. Oncologia Medica

Bologna, Italy

Location

IEO Istituto Europeo di Oncologia - Divisione Oncologia Medica

Milan, Italy

Location

Ospedale San Raffaele - U.O. di Oncologia Medica

Milan, Italy

Location

Istituto Nazionale Tumori Fondazione G. Pascale - Medical Oncology Thoraco-Pulmonary Department

Naples, Italy

Location

Istituto Nazionale Tumori Regina Elena IRCCS - S.C. Oncologia Medica B

Roma, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica

Rome, Italy

Location

Istituto Clinico Humanitas - U.O. di Oncologia Medica ed Ematologia

Rozzano, Italy

Location

National Cancer Center Hospital

Chūōku, Japan

Location

Kansai Medical University Hospital

Hirakata-shi, Japan

Location

National Cancer Center Hospital East

Kashiwa-shi, Japan

Location

Cancer Institute Hospital of JFCR

Kōtoku, Japan

Location

Kurume University Hospital

Kurume-shi, Japan

Location

Aichi Cancer Center Hospital

Nagoya, Japan

Location

Kindai University Hospital

Osakasayama-shi, Japan

Location

Kanagawa Cancer Center

Yokohama, Japan

Location

Asan Medical Center

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Severance Hospital, Yonsei University Health System - Division of Infectious Diseases

Seoul, South Korea

Location

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, South Korea

Location

Hospital Clinic de Barcelona - Servicio de Oncologia

Barcelona, Spain

Location

Hospital Universitari Vall d'Hebron - Oncology Dept.

Barcelona, Spain

Location

Hospital Universitario Reina Sofia - Dept of Oncology

Córdoba, Spain

Location

Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica

Madrid, Spain

Location

Hospital Universitario 12 de Octubre - Servicio de Oncologia

Madrid, Spain

Location

Hospital Universitario HM Madrid Sanchinarro - Servicio de Oncologia

Madrid, Spain

Location

Hospital Universitario La Paz - Oncology Department

Madrid, Spain

Location

Hospital Universitario Ramon y Cajal - Servicio de Oncologia

Madrid, Spain

Location

Hospital Regional Universitario de Malaga - Oncology Dept

Málaga, Spain

Location

Hospital Universitario Nuestra Señora de Valme - Servicio de Oncologia

Seville, Spain

Location

Hospital Universitario Virgen del Rocio - Oncology Service

Seville, Spain

Location

Hospital Universitario Virgen Macarena - Oncology Service

Seville, Spain

Location

Hospital Universitari i Politecnic La Fe - Oncology Department

Valencia, Spain

Location

Related Links

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Hereditary Sensory and Autonomic Neuropathies

Interventions

cemiplimab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Study Officials

• Medical Responsible

  Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2023
• First Posted: May 31, 2023
• Study Start: September 13, 2023
• Primary Completion: March 30, 2026
• Study Completion: March 30, 2026
• Last Updated: February 17, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (7); KR (4); ES (13); BE (6); DE (3); US (6); JP (8); FR (7)