Clinical trial NCT05882734: Tuvusertib (M1774) in Combination With Cemiplimab in Participants With Non-Squamous NSCLC (DDRiver NSCLC 322)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
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
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2023-05-31
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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..


Eligibility criteria: 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

Primary outcomes:
measure: Phase 1b/Phase 2a: Confirmed Overall response (OR) According to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 As assessed by Investigator
timeFrame: Time from randomization to final assessment or until progression disease, death, discontinuation criteria approximately up to 3 years and 2 months
measure: Phase 1b: Number of Participants With Adverse Events (AEs) and Treatment-related AEs
timeFrame: Time from randomization to final assessment at end of safety follow-up visit approximately up to 3 years and 2 months
Secondary outcomes:
measure: Phase 1b/Phase 2a: Duration of Response (DoR) According to RECIST 1.1 as Assessed by the Investigator
timeFrame: Time from randomization to final assessment or until progression disease, death, discontinuation criteria approximately up to 3 years and 2 months
measure: Phase 1b/Phase 2a: Progression Free Survival (PFS) According to RECIST 1.1 as Assessed by the Investigator
timeFrame: Time from randomization to final assessment or until progression disease, death, discontinuation criteria approximately up to 3 years and 2 months
measure: Phase 1b/Phase 2a: Overall survival (OS)
timeFrame: Time from randomization to final assessment or until progression disease, death, discontinuation criteria approximately up to 3 years and 2 months
measure: Phase 2a: Number of Participants With AEs and Treatment-related AEs
timeFrame: Time from randomization to final assessment at end of safety follow-up visit (approximately up to 3 years and 2 months)
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: UCLA Hematology and Oncology - Santa Monica
state: California
city: Pittsburgh
country: United States
facility: UPMC Cancer Center
state: Pennsylvania
city: Knoxville
country: United States
facility: Tennessee Cancer Specialists - Biomedical Research
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: Millennium Research &amp; Clinical Development
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Anderlecht
country: Belgium
facility: Institut Jules Bordet - Department of Institut Jules Bordet'
city: Edegem
country: Belgium
facility: UZA - Oncology
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis Hospital
city: Jette
country: Belgium
facility: Universitair Ziekenhuis Brussel - UZB
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liege
country: Belgium
facility: CHU de Liège - PARENT
city: Angers Cedex 9
country: France
facility: CHU Angers - Hôpital Larrey - Service de Pneumologie
city: Creteil Cedex
country: France
facility: Centre Hospitalier Intercommunal de Créteil - Service de Pneumologie
city: Limoges
country: France
facility: CHU Limoges - Hôpital Dupuytren - Unite d'Oncologie Thoracique et Cutanée
city: Marseille cedex 5
country: France
facility: Hôpital de la Timone - CPCEM CIC - Bat F 1er étage
city: Montpellier cedex 05
country: France
facility: Hopital Arnaud de Villeneuve - Service de Pneumologie-Addictologie
city: Pessac
country: France
facility: Groupe Hospitalier Sud - Hôpital Haut-Lévêque - Unité d'Explorations Fonctionnelles Respiratoires
city: Saint Herblain Cedex
country: France
facility: ICO - Site René Gauducheau - Service d'Oncologie medicale
city: Giessen
country: Germany
facility: Universitaetsklinikum Giessen und Marburg GmbH - Medizinische Klinik und Poliklinik III
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig AoeR - Med. Klinik u. Poliklinik I - Abt. Pneumologie
city: Offenbach
country: Germany
facility: Sana Klinikum Offenbach GmbH - Medizinische Klinik IV
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS - U.O. Oncologia Medica
city: Milano
country: Italy
facility: IEO Istituto Europeo di Oncologia - Divisione Oncologia Medica
city: Milano
country: Italy
facility: Ospedale San Raffaele - U.O. di Oncologia Medica
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G. Pascale - Medical Oncology Thoraco-Pulmonary Department
city: Roma
country: Italy
facility: Istituto Nazionale Tumori Regina Elena IRCCS - S.C. Oncologia Medica B
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas - U.O. di Oncologia Medica ed Ematologia
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
city: Hirakata-shi
country: Japan
facility: Kansai Medical University Hospital
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
city: Koto-ku
country: Japan
facility: Cancer Institute Hospital of JFCR
city: Kurume-shi
country: Japan
facility: Kurume University Hospital
city: Nagoya-shi
country: Japan
facility: Aichi Cancer Center Hospital
city: Osakasayama-shi
country: Japan
facility: Kindai University Hospital
city: Yokohama-shi
country: Japan
facility: Kanagawa Cancer Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System - Division of Infectious Diseases
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona - Servicio de Oncologia
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron - Oncology Dept.
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia - Dept of Oncology
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre - Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario HM Madrid Sanchinarro - Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario La Paz - Oncology Department
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal - Servicio de Oncologia
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Malaga - Oncology Dept
city: Sevilla
country: Spain
facility: Hospital Universitario Nuestra Señora de Valme - Servicio de Oncologia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio - Oncology Service
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena - Oncology Service
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe - Oncology Department
Study officials:
affiliation: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: