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

May 27, 2026 updated by: EMD Serono Research & Development Institute, Inc.

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)

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..

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

61

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Anderlecht, Belgium
        • Institut Jules Bordet - Department of Institut Jules Bordet'
      • Edegem, Belgium
        • UZA - Oncology
      • Hasselt, Belgium
        • Jessa Ziekenhuis Hospital
      • Jette, Belgium
        • Universitair Ziekenhuis Brussel - UZB
      • Leuven, Belgium
        • UZ Leuven
      • Liège, Belgium
        • CHU de Liège - PARENT
  • France
      • Angers, France
        • CHU Angers - Hôpital Larrey - Service de Pneumologie
      • Créteil, France
        • Centre Hospitalier Intercommunal de Créteil - Service de Pneumologie
      • Limoges, France
        • CHU Limoges - Hôpital Dupuytren - Unite d'Oncologie Thoracique et Cutanée
      • Marseille, France
        • Hôpital de la Timone - CPCEM CIC - Bat F 1er étage
      • Montpellier, France
        • Hopital Arnaud de Villeneuve - Service de Pneumologie-Addictologie
      • Pessac, France
        • Groupe Hospitalier Sud - Hôpital Haut-Lévêque - Unité d'Explorations Fonctionnelles Respiratoires
      • Saint-Herblain, France
        • ICO - Site René Gauducheau - Service d'Oncologie medicale
  • Germany
      • Giessen, Germany
        • Universitaetsklinikum Giessen und Marburg GmbH - Medizinische Klinik und Poliklinik III
      • Leipzig, Germany
        • Universitaetsklinikum Leipzig AoeR - Med. Klinik u. Poliklinik I - Abt. Pneumologie
      • Offenbach, Germany
        • Sana Klinikum Offenbach GmbH - Medizinische Klinik IV
  • Italy
      • Bologna, Italy
        • Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS - U.O. Oncologia Medica
      • Milan, Italy
        • IEO Istituto Europeo di Oncologia - Divisione Oncologia Medica
      • Milan, Italy
        • Ospedale San Raffaele - U.O. di Oncologia Medica
      • Naples, Italy
        • Istituto Nazionale Tumori Fondazione G. Pascale - Medical Oncology Thoraco-Pulmonary Department
      • Roma, Italy
        • Istituto Nazionale Tumori Regina Elena IRCCS - S.C. Oncologia Medica B
      • Rome, Italy
        • Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica
      • Rozzano, Italy
        • Istituto Clinico Humanitas - U.O. di Oncologia Medica ed Ematologia
  • Japan
      • Chūōku, Japan
        • National Cancer Center Hospital
      • Hirakata-shi, Japan
        • Kansai Medical University Hospital
      • Kashiwa-shi, Japan
        • National Cancer Center Hospital East
      • Kurume-shi, Japan
        • Kurume University Hospital
      • Kōtoku, Japan
        • Cancer Institute Hospital of Jfcr
      • Nagoya, Japan
        • Aichi Cancer Center Hospital
      • Osakasayama-shi, Japan
        • Kindai University Hospital
      • Yokohama, Japan
        • Kanagawa Cancer Center
  • South Korea
      • Seoul, South Korea
        • Asan Medical Center
      • Seoul, South Korea
        • Samsung Medical Center
      • Seoul, South Korea
        • The Catholic University of Korea, Seoul St. Mary's Hospital
      • Seoul, South Korea
        • Severance Hospital, Yonsei University Health System - Division of Infectious Diseases
  • Spain
      • Barcelona, Spain
        • Hospital Universitari Vall d'Hebron - Oncology Dept.
      • Barcelona, Spain
        • Hospital Clinic de Barcelona - Servicio de Oncologia
      • Córdoba, Spain
        • Hospital Universitario Reina Sofia - Dept of Oncology
      • Madrid, Spain
        • Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica
      • Madrid, Spain
        • Hospital Universitario HM Madrid Sanchinarro - Servicio de Oncologia
      • Madrid, Spain
        • Hospital Universitario 12 de Octubre - Servicio de Oncologia
      • Madrid, Spain
        • Hospital Universitario Ramon y Cajal - Servicio de Oncologia
      • Madrid, Spain
        • Hospital Universitario La Paz - Oncology Department
      • Málaga, Spain
        • Hospital Regional Universitario de Malaga - Oncology Dept
      • Seville, Spain
        • Hospital Universitario Virgen del Rocio - Oncology Service
      • Seville, Spain
        • Hospital Universitario Nuestra Señora de Valme - Servicio de Oncologia
      • Seville, Spain
        • Hospital Universitario Virgen Macarena - Oncology Service
      • Valencia, Spain
        • Hospital Universitari i Politecnic La Fe - Oncology Department
  • United States
    • California
      • Santa Monica, California, United States, 90404
        • UCLA Hematology and Oncology - Santa Monica
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC Cancer Center
    • Tennessee
      • Knoxville, Tennessee, United States, 37909
        • Tennessee Cancer Specialists - Biomedical Research
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas MD Anderson Cancer Center
      • Houston, Texas, United States, 77090
        • Millennium Research & Clinical Development
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists, PC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.
Other Names:
  • Tuvusertib
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.
Other Names:
  • Tuvusertib
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.
Other Names:
  • Tuvusertib
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.
Other Names:
  • Tuvusertib
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.
Other Names:
  • Tuvusertib
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.

What is the study measuring?

Primary Outcome Measures

Outcome 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 Frame: Time from randomization to final assessment or until progression disease, death, discontinuation criteria approximately up to 3 years and 2 months
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 Frame: Time from randomization to final assessment at end of safety follow-up visit approximately up to 3 years and 2 months
Time from randomization to final assessment at end of safety follow-up visit approximately up to 3 years and 2 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Phase 1b/Phase 2a: Duration of Response (DoR) According to RECIST 1.1 as Assessed by the Investigator
Time Frame: Time from randomization to final assessment or until progression disease, death, discontinuation criteria approximately up to 3 years and 2 months
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 Frame: Time from randomization to final assessment or until progression disease, death, discontinuation criteria approximately up to 3 years and 2 months
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 Frame: Time from randomization to final assessment or until progression disease, death, discontinuation criteria approximately up to 3 years and 2 months
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 Frame: Time from randomization to final assessment at end of safety follow-up visit (approximately up to 3 years and 2 months)
Time from randomization to final assessment at end of safety follow-up visit (approximately up to 3 years and 2 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

EMD Serono Research & Development Institute, Inc.

Collaborators

Merck KGaA, Darmstadt, Germany

Investigators

  • Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 13, 2023

Primary Completion (Estimated)

September 30, 2026

Study Completion (Estimated)

September 30, 2026

Study Registration Dates

First Submitted

May 22, 2023

First Submitted That Met QC Criteria

May 22, 2023

First Posted (Actual)

May 31, 2023

Study Record Updates

Last Update Posted (Actual)

May 28, 2026

Last Update Submitted That Met QC Criteria

May 27, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MS201924_0022
  • 2022-502010-85-00 (Other Identifier: EU Trial Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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