SAR408701 Versus Docetaxel in Previously Treated, Carcinoembryonic Antigen-related Cell Adhesion Molecule 5 (CEACAM5) Positive Metastatic Non-squamous Non-small-cell Lung Cancer Patients

Non-small Cell Lung Cancer Metastatic Clinical Trial

— CARMEN-LC03  

Official title:

Randomized, Open-label, Phase 3 Study of SAR408701 Versus Docetaxel in Previously Treated, Metastatic Nonsquamous, Non-small-cell Lung Cancer Patients With CEACAM5-positive Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04154956
• Other study ID #: EFC15858
• Secondary ID: U1111-1233-07812
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 6, 2020
• Est. completion date: August 26, 2026

Study information

• Verified date: February 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary Objectives:

• Study is designed with two primary endpoints that will be analyzed on randomized participants at the time of the cut-off date for each given analysis (progression free survival [PFS] and overall survival [OS])

• Study success is defined either on PFS or OS

• The primary objective is to determine whether tusamitamab ravtansine improves the progression free survival (PFS) when compared to docetaxel in participants with metastatic non-squamous non-small-cell lung cancer (NSCLC) expressing CEACAM5 greater than or equal to 2+ in intensity in at least 50% of the tumor cell population and previously treated with standard-of-care platinum-based chemotherapy and an immune checkpoint inhibitor (ICI)

• The primary objective is to determine whether tusamitamab ravtansine improves the overall survival (OS) when compared with docetaxel in participants with metastatic non-squamous NSCLC expressing CEACAM5 greater than or equal to 2+ in intensity in at least 50% of the tumor cell population and previously treated with standard-of-care platinum-based chemotherapy and an immune checkpoint inhibitor.

Secondary Objectives:

• To compare the objective response rate (ORR) of tusamitamab ravtansine with docetaxel

• To compare the health-related quality of life (HRQOL) of tusamitamab ravtansine with docetaxel

• To evaluate the safety of tusamitamab ravtansine compared to docetaxel

• To assess the duration of response (DOR) of tusamitamab ravtansine as compared with docetaxel

Description:

The expected duration of study intervention for participants who benefit from study intervention may vary, based on progression date; but median expected duration of study per participant is estimated as median 9 months in docetaxel arm (1 month for screening, 4 months for treatment, and 4 months for the EOT and follow-up visits) and 12.5 months in SAR408701 arm (1 month for screening, 6.5 months for treatment, and 5 months for end of treatment follow-up).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 411
• Est. completion date: August 26, 2026
• Est. primary completion date: September 22, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• At least 18 years of age or above (or country's legal age of maturity if above 18 years) and signed the informed consent.

• Histologically or cytologically proven diagnosis of non-squamous NSCLC with metastatic disease at study entry; progression after platinum-based chemotherapy and immune checkpoint inhibitor.

• Participants with carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 5 expression of greater than or equal to 2+ in archival tumor sample (or if not available, fresh biopsy sample) involving at least 50% of the tumor cell population as demonstrated prospectively by central laboratory via immune histochemistry (IHC).

• At least one measurable lesion by RECIST v1.1 as determined by local site investigator /radiologist assessment.

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

• A female participant who agrees to use highly effective contraceptive methods during and for at least 7 months after the last dose of study intervention.

• A male participant who agrees to use highly effective contraception methods during and for at least 6 months after the last dose of study intervention.

Exclusion Criteria:

• Patients with untreated brain metastases and history of leptomeningeal disease. if previously treated brain metastases no documentation of non-progressive disease in brain by imaging performed at least 4 weeks after CNS directed treatment and at least 2 weeks prior to the first dose of study intervention.

• Significant concomitant illnesses, including all severe medical conditions that would impair the patient's participation in the study or interpretation of the results.

• History within the last 3 years of an invasive malignancy other than the one treated in this study, with the exception of resected/ablated basal or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix, or other local tumors considered cured by local treatment.

• Non-resolution of any prior treatment related toxicity to less than grade 2 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (V) 5.0, except for alopecia, vitiligo and active thyroiditis controlled with hormonal replacement therapy

• History of known acquired immunodeficiency syndrome (AIDS) related illnesses or known HIV disease requiring antiretroviral treatment, or unresolved viral hepatitis

• Previous history of and/or unresolved corneal disorders. The use of contact lenses is not permitted.

• Concurrent treatment with any other anticancer therapy.

• Prior treatment with docetaxel or maytansinoid derivatives (DM1 or DM4 antibody drug conjugate) or any drug targeting CEACAM5.

• Contraindication to use of corticosteroid premedication.

• Previous enrollment in this study and current participation in any other clinical study involving an investigational study treatment or any other type of medical research.

• Poor bone marrow, liver or kidney functions

• Hypersensitivity to any of the study interventions, or components thereof (EDTA), or drug (paclitaxel, polysorbate 80) or other allergy that, in the opinion of the Investigator, contraindicates participation in the study.

The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Related Conditions & MeSH terms

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

Intervention

Drug:
• SAR408701
Pharmaceutical form: Concentrate for solution for intravenous infusion Route of administration: intravenous (IV) infusion
• Docetaxel
Pharmaceutical form: Concentrate for solution for intravenous infusion Route of administration: IV infusion

Locations

Country	Name	City	State
Argentina	Investigational Site Number : 0320001	Buenos Aires
Argentina	Investigational Site Number : 0320004	Buenos Aires
Argentina	Investigational Site Number : 0320009	Caba	Buenos Aires
Argentina	Investigational Site Number : 0320012	Capital Federal	Buenos Aires
Argentina	Investigational Site Number : 0320014	Ciudad De Cordoba
Argentina	Investigational Site Number : 0320008	Pergamino	Buenos Aires
Argentina	Investigational Site Number : 0320005	Rosario	Santa Fe
Argentina	Investigational Site Number : 0320002	Salta
Argentina	Investigational Site Number : 0320003	Viedma	Río Negro
Australia	Investigational Site Number : 0360002	Blacktown	New South Wales
Australia	Investigational Site Number : 0360003	Waratah	New South Wales
Australia	Investigational Site Number : 0360001	Woolloongabba	Queensland
Belgium	Investigational Site Number : 0560006	Anderlecht
Belgium	Investigational Site Number : 0560007	Charleroi
Belgium	Investigational Site Number : 0560004	Edegem
Belgium	Investigational Site Number : 0560005	Gent
Belgium	Investigational Site Number : 0560001	Leuven
Belgium	Investigational Site Number : 0560003	Liège
Belgium	Investigational Site Number : 0560002	Sint-Lambrechts-Woluwe
Brazil	Clínica de Oncologia Reichow Site Number : 0760023	Blumenau	Santa Catarina
Brazil	Instituto De Oncologia Parana Site Number : 0760008	Curitiba	Paraná
Brazil	Centro Regional Integrado De Oncologia - CRIO Site Number : 0760002	Fortaleza	Ceará
Brazil	Centro Avancado de Oncologia CECAN - Liga Contra o Cancer Site Number : 0760026	Natal	Rio Grande Do Norte
Brazil	Hospital Mae de Deus Site Number : 0760012	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital Sao Lucas da PUCRS Site Number : 0760005	Porto Alegre	Rio Grande Do Sul
Brazil	OC ONCOCLINICAS BOTAFOGO Site Number : 0760025	Rio de Janeiro
Brazil	Hospital de Base Sao Jose do Rio Preto Site Number : 0760001	Sao Jose do Rio Preto	São Paulo
Brazil	A Beneficencia Portuguesa de Sao Paulo - Hospital Beneficencia Portuguesa - BP Mirante Site Number : 0760024	Sao Paulo	São Paulo
Brazil	Hospital Alemao Oswaldo Cruz Site Number : 0760022	Sao Paulo	São Paulo
Brazil	Hospital Sirio Libanes Site Number : 0760018	Sao Paulo	São Paulo
Brazil	IEP - Instituto de Ensino e Pesquisa Sao Lucas Site Number : 0760010	Sao Paulo	São Paulo
Brazil	Nucleo de Pesquisa Clinica e Ensino da Rede Sao Camilo Site Number : 0760007	Sao Paulo	São Paulo
Bulgaria	Investigational Site Number : 1000008	Burgas
Bulgaria	Investigational Site Number : 1000010	Pleven
Bulgaria	Investigational Site Number : 1000007	Plovdiv
Bulgaria	Investigational Site Number : 1000001	Sofia
Bulgaria	Investigational Site Number : 1000002	Sofia
Bulgaria	Investigational Site Number : 1000003	Sofia
Bulgaria	Investigational Site Number : 1000004	Sofia
Bulgaria	Investigational Site Number : 1000005	Sofia
Canada	Investigational Site Number : 1240003	Greenfield Park	Quebec
Canada	Investigational Site Number : 1240008	Halifax	Nova Scotia
Canada	Investigational Site Number : 1240009	Montreal	Quebec
Canada	Investigational Site Number : 1240010	Montreal	Quebec
Chile	Investigational Site Number : 1520002	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520004	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520006	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520007	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520009	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520005	Temuco	La Araucanía
Chile	Investigational Site Number : 1520001	Viña del Mar	Valparaíso
China	Investigational Site Number : 1560026	Beijing
China	Investigational Site Number : 1560027	Beijing
China	Investigational Site Number : 1560029	Beijing
China	Investigational Site Number : 1560030	Beijing
China	Investigational Site Number : 1560042	Beijing
China	Investigational Site Number : 1560009	Changchun
China	Investigational Site Number : 1560010	Changchun
China	Investigational Site Number : 1560015	Changsha
China	Investigational Site Number : 1560039	Changsha
China	Investigational Site Number : 1560032	Chengdu
China	Investigational Site Number : 1560038	Chengdu
China	Investigational Site Number : 1560043	Chongqing
China	Investigational Site Number : 1560044	Chongqing
China	Investigational Site Number : 1560024	Fuzhou
China	Investigational Site Number : 1560051	Ganzhou
China	Investigational Site Number : 1560001	Guangzhou
China	Investigational Site Number : 1560017	Guangzhou
China	Investigational Site Number : 1560034	Guangzhou
China	Investigational Site Number : 1560036	Guangzhou
China	Investigational Site Number : 1560037	Guangzhou
China	Investigational Site Number : 1560011	Hangzhou
China	Investigational Site Number : 1560018	Hangzhou
China	Investigational Site Number : 1560021	Hangzhou
China	Investigational Site Number : 1560025	Hangzhou
China	Investigational Site Number : 1560033	Hangzhou
China	Investigational Site Number : 1560005	Harbin
China	Investigational Site Number : 1560004	Hefei
China	Investigational Site Number : 1560014	Hefei
China	Investigational Site Number : 1560050	Huizhou
China	Investigational Site Number : 1560028	Jinan
China	Investigational Site Number : 1560047	Jinan
China	Investigational Site Number : 1560035	Nanchang
China	Investigational Site Number : 1560019	Nanjing
China	Investigational Site Number : 1560023	Nanjing
China	Investigational Site Number : 1560012	Nanning
China	Investigational Site Number : 1560045	Tianjin
China	Investigational Site Number : 1560006	Wuhan
China	Investigational Site Number : 1560016	Zhanjiang
China	Investigational Site Number : 1560040	Zhengzhou
China	Investigational Site Number : 1560041	Zhengzhou
China	Investigational Site Number : 1560048	Zhongshan
France	Investigational Site Number : 2500010	Bordeaux Cedex
France	Investigational Site Number : 2500008	CAEN Cedex 05
France	Investigational Site Number : 2500006	Creteil
France	Investigational Site Number : 2500005	Dijon
France	Investigational Site Number : 2500007	GRENOBLE Cedex 9
France	Investigational Site Number : 2500001	Marseille
France	Investigational Site Number : 2500013	Montpellier
France	Investigational Site Number : 2500011	Paris
France	Investigational Site Number : 2500014	Paris
France	Investigational Site Number : 2500009	Pierre Benite
France	Investigational Site Number : 2500003	RENNES Cedex 09
France	Investigational Site Number : 2500012	Saint Herblain
France	Investigational Site Number : 2500002	Saint-mande
France	Investigational Site Number : 2500004	Villejuif
Germany	Investigational Site Number : 2760002	Essen
Germany	Investigational Site Number : 2760001	Heidelberg
Germany	Investigational Site Number : 2760003	Oldenburg
Greece	Investigational Site Number : 3000001	Athens
Greece	Investigational Site Number : 3000005	Athens
Greece	Investigational Site Number : 3000003	Heraklion
Greece	Investigational Site Number : 3000004	Ioannina
Greece	Investigational Site Number : 3000002	Larissa
Greece	Investigational Site Number : 3000006	Thessaloniki
Hungary	Investigational Site Number : 3480003	Budapest
Hungary	Investigational Site Number : 3480004	Budapest
Hungary	Investigational Site Number : 3480007	Budapest
Hungary	Investigational Site Number : 3480005	Kaposvár
India	Investigational Site Number : 3560010	Bhubaneswar
India	Investigational Site Number : 3560008	Jaipur
India	Investigational Site Number : 3560007	New Delhi
India	Investigational Site Number : 3560001	Pune
India	Investigational Site Number : 3560006	Pune
Israel	Investigational Site Number : 3760001	Haifa
Israel	Investigational Site Number : 3760002	Kfar-Saba
Israel	Investigational Site Number : 3760003	Petach Tikva
Italy	Investigational Site Number : 3800007	Aviano (PN)	Friuli-Venezia Giulia
Italy	Investigational Site Number : 3800006	Catania
Italy	Investigational Site Number : 3800001	Milano
Italy	Investigational Site Number : 3800003	Orbassano	Torino
Italy	Investigational Site Number : 3800004	Ravenna	Emilia-Romagna
Italy	Investigational Site Number : 3800005	Rozzano	Milano
Japan	Investigational Site Number : 3920011	Bunkyo-ku	Tokyo
Japan	Investigational Site Number : 3920012	Fukuoka-shi	Fukuoka
Japan	Investigational Site Number : 3920017	Himeji-shi	Hyogo
Japan	Investigational Site Number : 3920001	Hirakata-shi	Osaka
Japan	Investigational Site Number : 3920006	Kanazawa-shi	Ishikawa
Japan	Investigational Site Number : 3920008	Kurume-shi	Fukuoka
Japan	Investigational Site Number : 3920018	Mitaka-shi	Tokyo
Japan	Investigational Site Number : 3920002	Nagoya-shi	Aichi
Japan	Investigational Site Number : 3920015	Nagoya-shi	Aichi
Japan	Investigational Site Number : 3920009	Natori-shi	Miyagi
Japan	Investigational Site Number : 3920013	Osaka Sayama-shi	Osaka
Japan	Investigational Site Number : 3920003	Osaka-shi	Osaka
Japan	Investigational Site Number : 3920014	Sakai-shi	Osaka
Japan	Investigational Site Number : 3920016	Sapporo-shi	Hokkaido
Japan	Investigational Site Number : 3920004	Sunto-gun	Shizuoka
Japan	Investigational Site Number : 3920010	Ube-shi	Yamaguchi
Japan	Investigational Site Number : 3920007	Wakayama-shi	Wakayama
Japan	Investigational Site Number : 3920005	Yokohama-shi	Kanagawa
Korea, Republic of	Investigational Site Number : 4100008	Busan	Busan-gwangyeoksi
Korea, Republic of	Investigational Site Number : 4100005	Cheongju-si	Chungcheongbuk-do
Korea, Republic of	Investigational Site Number : 4100001	Seoul
Korea, Republic of	Investigational Site Number : 4100003	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 4100004	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 4100006	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 4100007	Seoul	Seoul-teukbyeolsi
Lithuania	Investigational Site Number : 4400003	Kaunas
Lithuania	Investigational Site Number : 4400001	Vilnius
Mexico	Investigational Site Number : 4840009	Ciudad de Mexico
Mexico	Investigational Site Number : 4840003	Cuauhtémoc	Ciudad De Mexico
Mexico	Investigational Site Number : 4840004	Guadalajara	Jalisco
Mexico	Investigational Site Number : 4840008	San Luis Potosi	San Luis Potosí
Netherlands	Investigational Site Number : 5280003	's Hertogenbosch
Netherlands	Investigational Site Number : 5280004	Breda
Netherlands	Investigational Site Number : 5280005	Utrecht
Poland	Investigational Site Number : 6160004	Olsztyn	Warminsko-mazurskie
Poland	Investigational Site Number : 6160001	Warsaw
Portugal	Investigational Site Number : 6200002	Almada
Portugal	Investigational Site Number : 6200001	Lisboa
Portugal	Investigational Site Number : 6200004	Lisboa
Portugal	Investigational Site Number : 6200005	Porto
Portugal	Investigational Site Number : 6200006	Porto
Romania	Investigational Site Number : 6420008	Alba Iulia
Romania	Investigational Site Number : 6420009	Brasov
Romania	Investigational Site Number : 6420003	Bucaresti
Romania	Investigational Site Number : 6420002	Bucuresti
Romania	Investigational Site Number : 6420011	Cluj
Romania	Investigational Site Number : 6420010	Cluj-Napoca
Romania	Investigational Site Number : 6420006	Craiova
Romania	Investigational Site Number : 6420012	Otopeni
Romania	Investigational Site Number : 6420004	Timisoara
Romania	Investigational Site Number : 6420005	Timisoara
Russian Federation	Investigational Site Number : 6430001	Moscow
Russian Federation	Investigational Site Number : 6430003	Saint -Petersburg
Singapore	Investigational Site Number : 7020001	Singapore
Singapore	Investigational Site Number : 7020002	Singapore
Spain	Investigational Site Number : 7240005	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240007	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240001	Hospitalet de Llobregat	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240002	Madrid
Spain	Investigational Site Number : 7240106	Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7240009	Madrid / Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7240010	Majadahonda	Madrid
Spain	Investigational Site Number : 7240004	Málaga
Spain	Investigational Site Number : 7240006	Pamplona	Navarra
Spain	Investigational Site Number : 7240011	Sevilla
Spain	Investigational Site Number : 7240008	Valencia
Turkey	Investigational Site Number : 7920002	Adana
Turkey	Investigational Site Number : 7920008	Adana
Turkey	Investigational Site Number : 7920012	Adana
Turkey	Investigational Site Number : 7920011	Ankara
Turkey	Investigational Site Number : 7920001	Istanbul
Turkey	Investigational Site Number : 7920005	Istanbul
Turkey	Investigational Site Number : 7920006	Istanbul
Turkey	Investigational Site Number : 7920007	Izmir
Turkey	Investigational Site Number : 7920010	Izmir
Turkey	Investigational Site Number : 7920014	Kocaeli
Turkey	Investigational Site Number : 7920009	Malatya
United Kingdom	Investigational Site Number : 8260002	London
United Kingdom	Investigational Site Number : 8260004	Truro	Cornwall
United States	Roswell Park Cancer Institute Site Number : 8400011	Buffalo	New York
United States	National Jewish Health Site Number : 8400033	Denver	Colorado
United States	Renovatio Clinical Site Number : 8400032	El Paso	Texas
United States	Florida Cancer Specialists South Division Site Number : 8400020	Fort Myers	Florida
United States	Ca & Hem Center Of W Michigan Site Number : 8400016	Grand Rapids	Michigan
United States	Thompson Cancer Survival Center Site Number : 8400038	Knoxville	Tennessee
United States	Bon Secours St. Francis Medical Center Site Number : 8400035	Midlothian	Virginia
United States	Medical College of Wisconsin Site Number : 8400006	Milwaukee	Wisconsin
United States	Tennessee Oncology Nashville Site Number : 8400003	Nashville	Tennessee
United States	Florida Cancer Specialists North Division Site Number : 8400019	Saint Petersburg	Florida
United States	Renovatio Clinical Site Number : 8400013	The Woodlands	Texas
United States	Lankenau Hospital Cancer Center Site Number : 8400017	Wynnewood	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  China,  France,  Germany,  Greece,  Hungary,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Lithuania,  Mexico,  Netherlands,  Poland,  Portugal,  Romania,  Russian Federation,  Singapore,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival (PFS)	PFS will be defined as the time from randomization to the date of the first documented disease progression or death of any cause, whichever comes first.	Baseline to up to approximately 15 months
Primary	Overall Survival (OS)	OS will be defined as the time of randomization to the date of death due to any cause.	Baseline up to approximately 2 years
Secondary	Objective response rate (ORR)	Objective response rate will be defined as the proportion of participants who have a complete response (CR) or partial response (PR), as best overall response derived from Overall Response (OR) determined by the Independent Radiology Review Committee (IRC) per Response Evaluation Criteria in Solid Tumor (RECIST) 1.1	Baseline up to approximately 2 years
Secondary	Health related quality of life (HRQOL) - disease related symptoms	Time to deterioration (TTD) in disease related symptoms as determined by European Organization for Research and Treatment for Cancer (EORTC)- Quality of life Questionnaire (QLQ)-Lung Cancer (LC)13	Baseline up to median 12 months
Secondary	Health related quality of life (HRQOL) - physical function	TTD in physical function as determined by EORTC QLQ C30	Baseline up to median 12 months
Secondary	Health related quality of life (HRQOL) - role function	TTD in role function as determined by EORTC QLQ C30	Baseline up to median 12 months
Secondary	Number of participants with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)	Incidence of TEAEs and SAEs and laboratory abnormalities according to NCI CTCAE V5	Baseline up to end of study (approximately 2 years)
Secondary	Duration of response (DOR)	Duration of response (DOR) is defined as the time from first documented evidence of complete response (CR) or partial response (PR) until progressive disease (PD) determined per RECIST 1.1 or death from any cause, whichever occurs first.	Baseline up to approximately 2 years