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

September 9, 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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
61

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
EMD Serono Research & Development Institute, Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Merck KGaA, Darmstadt, Germany

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 13, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 15, 2026

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 15, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 22, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 22, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 31, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 14, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 9, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MS201924_0022
  • 2022-502010-85-00 (Other Identifier: EU Trial Number)
  • jRCT2031230332 (Other Identifier: JRCT (Japan))
  • CTR20242324 (Other Identifier: ChinaDrugTrials.org.cn)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

IPD will not be shared for Phase I interventional or observational studies.

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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