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

Non-Small Cell Lung Cancer Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05882734
• Other study ID #: MS201924_0022
• Secondary ID: 2022-502010-85-0
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 13, 2023
• Est. completion date: September 3, 2026

Study information

• Verified date: April 2024
• Source: EMD Serono
• Contact: US Medical Information
• Phone: 888-275-7376
• Email: eMediUSA[@]emdserono.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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..

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: September 3, 2026
• Est. primary completion date: August 25, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

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.
• 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.

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet - Department of Institut Jules Bordet'	Anderlecht
Belgium	UZA - Oncology	Edegem
Belgium	Jessa Ziekenhuis Hospital	Hasselt
Belgium	Universitair Ziekenhuis Brussel - UZB	Jette
France	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	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
Germany	Universitaetsklinikum Giessen und Marburg GmbH - Medizinische Klinik und Poliklinik III	Giessen
Italy	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
Japan	National Cancer Center Hospital	Chuo-ku
Japan	Kansai Medical University Hospital	Hirakata-shi
Japan	National Cancer Center Hospital East	Kashiwa-shi
Japan	Cancer Institute Hospital of JFCR	Koto-ku
Japan	Kurume University Hospital	Kurume-shi
Japan	Aichi Cancer Center Hospital	Nagoya-shi
Japan	Kindai University Hospital	Osakasayama-shi
Japan	Kanagawa Cancer Center	Yokohama-shi
Korea, Republic of	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
Spain	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 La Paz - Oncology Department	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
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Millennium Research & Clinical Development	Houston	Texas
United States	Tennessee Cancer Specialists - Biomedical Research	Knoxville	Tennessee
United States	UPMC Cancer Center	Pittsburgh	Pennsylvania
United States	UCLA Hematology and Oncology - Santa Monica	Santa Monica	California

Sponsors (2)

Lead Sponsor	Collaborator
EMD Serono Research & Development Institute, Inc.	Merck KGaA, Darmstadt, Germany

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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)

External Links

•   Trial Awareness and Transparency website