Tuvusertib (M1774) in Combination With Cemiplimab in Participants With Non-Squamous NSCLC (DDRiver NSCLC 322)
- Conditions
- Non-Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT05882734
- 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..
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 180
-
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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dosing Regimen 1 (Phase 1b): M1774 + Cemiplimab Cemiplimab - Dosing Regimen 1 (Phase 1b): M1774 + Cemiplimab M1774 - Stratum B (Phase 2a): Either Dosing Regimen 1 or 2 as finalized in Phase 1b M1774 - Dosing Regimen 2 (Phase 1b): M1774 + Cemiplimab M1774 - Dosing Regimen 2 (Phase 1b): M1774 + Cemiplimab Cemiplimab - Stratum A (Phase 2a): Either Dosing Regimen 1 or 2 as finalized in Phase 1b Cemiplimab - Stratum C (Phase 2a): Either Dosing Regimen 1 or 2 as finalized in Phase 1b Cemiplimab - Stratum A (Phase 2a): Either Dosing Regimen 1 or 2 as finalized in Phase 1b M1774 - Stratum C (Phase 2a): Either Dosing Regimen 1 or 2 as finalized in Phase 1b M1774 - Stratum B (Phase 2a): Either Dosing Regimen 1 or 2 as finalized in Phase 1b Cemiplimab -
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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)
Trial Locations
- Locations (54)
CHU de Liège - PARENT
🇧🇪Liege, Belgium
UPMC Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
UCLA Hematology and Oncology - Santa Monica
🇺🇸Santa Monica, California, United States
Tennessee Cancer Specialists - Biomedical Research
🇺🇸Knoxville, Tennessee, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Millennium Research & Clinical Development
🇺🇸Houston, Texas, United States
Virginia Cancer Specialists, PC
🇺🇸Fairfax, Virginia, United States
Institut Jules Bordet - Department of Institut Jules Bordet'
🇧🇪Anderlecht, Belgium
UZA - Oncology
🇧🇪Edegem, Belgium
Jessa Ziekenhuis Hospital
🇧🇪Hasselt, Belgium
Universitair Ziekenhuis Brussel - UZB
🇧🇪Jette, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
CHU Angers - Hôpital Larrey - Service de Pneumologie
🇫🇷Angers Cedex 9, France
Centre Hospitalier Intercommunal de Créteil - Service de Pneumologie
🇫🇷Creteil Cedex, France
CHU Limoges - Hôpital Dupuytren - Unite d'Oncologie Thoracique et Cutanée
🇫🇷Limoges, France
Hôpital de la Timone - CPCEM CIC - Bat F 1er étage
🇫🇷Marseille cedex 5, France
Hopital Arnaud de Villeneuve - Service de Pneumologie-Addictologie
🇫🇷Montpellier cedex 05, France
Groupe Hospitalier Sud - Hôpital Haut-Lévêque - Unité d'Explorations Fonctionnelles Respiratoires
🇫🇷Pessac, France
ICO - Site René Gauducheau - Service d'Oncologie medicale
🇫🇷Saint Herblain Cedex, France
Universitaetsklinikum Giessen und Marburg GmbH - Medizinische Klinik und Poliklinik III
🇩🇪Giessen, Germany
Universitaetsklinikum Leipzig AoeR - Med. Klinik u. Poliklinik I - Abt. Pneumologie
🇩🇪Leipzig, Germany
Sana Klinikum Offenbach GmbH - Medizinische Klinik IV
🇩🇪Offenbach, Germany
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS - U.O. Oncologia Medica
🇮🇹Bologna, Italy
IEO Istituto Europeo di Oncologia - Divisione Oncologia Medica
🇮🇹Milano, Italy
Ospedale San Raffaele - U.O. di Oncologia Medica
🇮🇹Milano, Italy
Istituto Nazionale Tumori Fondazione G. Pascale - Medical Oncology Thoraco-Pulmonary Department
🇮🇹Napoli, Italy
Istituto Nazionale Tumori Regina Elena IRCCS - S.C. Oncologia Medica B
🇮🇹Roma, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica
🇮🇹Rome, Italy
Istituto Clinico Humanitas - U.O. di Oncologia Medica ed Ematologia
🇮🇹Rozzano, Italy
National Cancer Center Hospital
🇯🇵Chuo-ku, Japan
Kansai Medical University Hospital
🇯🇵Hirakata-shi, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa-shi, Japan
Kurume University Hospital
🇯🇵Kurume-shi, Japan
Cancer Institute Hospital of JFCR
🇯🇵Koto-ku, Japan
Aichi Cancer Center Hospital
🇯🇵Nagoya-shi, Japan
Kindai University Hospital
🇯🇵Osakasayama-shi, Japan
Kanagawa Cancer Center
🇯🇵Yokohama-shi, Japan
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System - Division of Infectious Diseases
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Hospital Clinic de Barcelona - Servicio de Oncologia
🇪🇸Barcelona, Spain
Hospital Universitari Vall d'Hebron - Oncology Dept.
🇪🇸Barcelona, Spain
Hospital Universitario Reina Sofia - Dept of Oncology
🇪🇸Córdoba, Spain
Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre - Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Universitario HM Madrid Sanchinarro - Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Universitario La Paz - Oncology Department
🇪🇸Madrid, Spain
Hospital Universitario Ramon y Cajal - Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Regional Universitario de Malaga - Oncology Dept
🇪🇸Málaga, Spain
Hospital Universitario Nuestra Señora de Valme - Servicio de Oncologia
🇪🇸Sevilla, Spain
Hospital Universitario Virgen del Rocio - Oncology Service
🇪🇸Sevilla, Spain
Hospital Universitario Virgen Macarena - Oncology Service
🇪🇸Sevilla, Spain
Hospital Universitari i Politecnic La Fe - Oncology Department
🇪🇸Valencia, Spain