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

NCT ID: NCT05882734

Last Updated: 2025-10-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

61 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-09-13

Study Completion Date

2026-03-30

Brief Summary

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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..

Detailed Description

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Conditions

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Non-Small Cell Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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

Group Type EXPERIMENTAL

M1774

Intervention Type 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.

Cemiplimab

Intervention Type 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 2 (Phase 1b): M1774 + Cemiplimab

Group Type EXPERIMENTAL

M1774

Intervention Type 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.

Cemiplimab

Intervention Type 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.

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

Group Type EXPERIMENTAL

M1774

Intervention Type 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.

Cemiplimab

Intervention Type 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.

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

Group Type EXPERIMENTAL

M1774

Intervention Type 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.

Cemiplimab

Intervention Type 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.

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

Group Type EXPERIMENTAL

M1774

Intervention Type 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.

Cemiplimab

Intervention Type 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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Tuvusertib

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role collaborator

EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Responsible

Role: STUDY_DIRECTOR

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

Locations

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UCLA Hematology and Oncology - Santa Monica

Santa Monica, California, United States

Site Status

UPMC Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

Tennessee Cancer Specialists - Biomedical Research

Knoxville, Tennessee, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Millennium Research & Clinical Development

Houston, Texas, United States

Site Status

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Site Status

Institut Jules Bordet - Department of Institut Jules Bordet'

Anderlecht, , Belgium

Site Status

UZA - Oncology

Edegem, , Belgium

Site Status

Jessa Ziekenhuis Hospital

Hasselt, , Belgium

Site Status

Universitair Ziekenhuis Brussel - UZB

Jette, , Belgium

Site Status

UZ Leuven

Leuven, , Belgium

Site Status

CHU de Liège - PARENT

Liège, , Belgium

Site Status

CHU Angers - Hôpital Larrey - Service de Pneumologie

Angers, , France

Site Status

Centre Hospitalier Intercommunal de Créteil - Service de Pneumologie

Créteil, , France

Site Status

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

Limoges, , France

Site Status

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

Marseille, , France

Site Status

Hopital Arnaud de Villeneuve - Service de Pneumologie-Addictologie

Montpellier, , France

Site Status

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

Pessac, , France

Site Status

ICO - Site René Gauducheau - Service d'Oncologie medicale

Saint-Herblain, , France

Site Status

Universitaetsklinikum Giessen und Marburg GmbH - Medizinische Klinik und Poliklinik III

Giessen, , Germany

Site Status

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

Leipzig, , Germany

Site Status

Sana Klinikum Offenbach GmbH - Medizinische Klinik IV

Offenbach, , Germany

Site Status

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

Bologna, , Italy

Site Status

IEO Istituto Europeo di Oncologia - Divisione Oncologia Medica

Milan, , Italy

Site Status

Ospedale San Raffaele - U.O. di Oncologia Medica

Milan, , Italy

Site Status

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

Napoli, , Italy

Site Status

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

Roma, , Italy

Site Status

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica

Rome, , Italy

Site Status

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

Rozzano, , Italy

Site Status

National Cancer Center Hospital

Chūōku, , Japan

Site Status

Kansai Medical University Hospital

Hirakata-shi, , Japan

Site Status

National Cancer Center Hospital East

Kashiwa-shi, , Japan

Site Status

Cancer Institute Hospital of JFCR

Kōtoku, , Japan

Site Status

Kurume University Hospital

Kurume-shi, , Japan

Site Status

Aichi Cancer Center Hospital

Nagoya, , Japan

Site Status

Kindai University Hospital

Osakasayama-shi, , Japan

Site Status

Kanagawa Cancer Center

Yokohama, , Japan

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

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

Seoul, , South Korea

Site Status

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

Seoul, , South Korea

Site Status

Hospital Clinic de Barcelona - Servicio de Oncologia

Barcelona, , Spain

Site Status

Hospital Universitari Vall d'Hebron - Oncology Dept.

Barcelona, , Spain

Site Status

Hospital Universitario Reina Sofia - Dept of Oncology

Córdoba, , Spain

Site Status

Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre - Servicio de Oncologia

Madrid, , Spain

Site Status

Hospital Universitario HM Madrid Sanchinarro - Servicio de Oncologia

Madrid, , Spain

Site Status

Hospital Universitario La Paz - Oncology Department

Madrid, , Spain

Site Status

Hospital Universitario Ramon y Cajal - Servicio de Oncologia

Madrid, , Spain

Site Status

Hospital Regional Universitario de Malaga - Oncology Dept

Málaga, , Spain

Site Status

Hospital Universitario Nuestra Señora de Valme - Servicio de Oncologia

Seville, , Spain

Site Status

Hospital Universitario Virgen del Rocio - Oncology Service

Seville, , Spain

Site Status

Hospital Universitario Virgen Macarena - Oncology Service

Seville, , Spain

Site Status

Hospital Universitari i Politecnic La Fe - Oncology Department

Valencia, , Spain

Site Status

Countries

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United States Belgium France Germany Italy Japan South Korea Spain

Related Links

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https://medical.emdserono.com/en_US/home.html

US Medical Information website, Medical Resources

Other Identifiers

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2022-502010-85-00

Identifier Type: OTHER

Identifier Source: secondary_id

MS201924_0022

Identifier Type: -

Identifier Source: org_study_id

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