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

NCT ID: NCT04154956

Last Updated: 2025-08-05

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 389 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-06
• Study Completion Date: 2026-03-31

Brief Summary

Primary Objectives:

• Study was designed with multiple primary endpoints 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 was defined either on PFS or OS
• The primary objective was 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 was 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:

• Compared the objective response rate (ORR) of tusamitamab ravtansine with docetaxel
• Compared the health-related quality of life (HRQOL) of tusamitamab ravtansine with docetaxel
• Evaluated the safety of tusamitamab ravtansine compared to docetaxel
• Assessed the duration of response (DOR) of tusamitamab ravtansine as compared with docetaxel

Detailed Description

The median expected duration of study per participant was 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).

Conditions

Non-small Cell Lung Cancer Metastatic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SAR408701 (tusamitamab ravtansine)

Participants received tusamitamab ravtansine 100 milligrams per square meter (mg/m\^2) by intravenous (IV) infusion, once every 2 weeks (Q2W) until objective progressive disease (PD), unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 147 weeks).

Group Type: EXPERIMENTAL

SAR408701

Intervention Type: DRUG

Pharmaceutical form: Concentrate for solution for intravenous infusion Route of administration: intravenous (IV) infusion

Docetaxel

Participants received docetaxel 75 mg/m\^2 by IV infusion, once every 3 weeks (Q3W) until objective PD, unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 115 weeks).

Group Type: ACTIVE_COMPARATOR

Docetaxel

Intervention Type: DRUG

Pharmaceutical form: Concentrate for solution for intravenous infusion Route of administration: IV infusion

Interventions

SAR408701

Pharmaceutical form: Concentrate for solution for intravenous infusion Route of administration: intravenous (IV) infusion

Intervention Type: DRUG

Docetaxel

Pharmaceutical form: Concentrate for solution for intravenous infusion Route of administration: IV infusion

Intervention Type: DRUG

Other Intervention Names

TAXOTERE

Eligibility Criteria

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 agreed to use highly effective contraceptive methods during and for at least 7 months after the last dose of study intervention.
• A male participant who agreed to use highly effective contraception methods during and for at least 6 months after the last dose of study intervention.

Exclusion Criteria

• Participants 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 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 was 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.
• Contraindicated the 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, contraindicated participation in the study.

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Florida Cancer Specialists South Division- Site Number : 8400020

Fort Myers, Florida, United States

Florida Cancer Specialists North Division- Site Number : 8400019

St. Petersburg, Florida, United States

Ca & Hem Center Of W Michigan- Site Number : 8400016

Grand Rapids, Michigan, United States

Roswell Park Cancer Institute Site Number : 8400011

Buffalo, New York, United States

Lankenau Hospital Cancer Center- Site Number : 8400017

Wynnewood, Pennsylvania, United States

Renovatio Clinical- Site Number : 8400032

El Paso, Texas, United States

Renovatio Clinical - Site Number : 8400013

The Woodlands, Texas, United States

Medical College of Wisconsin- Site Number : 8400006

Milwaukee, Wisconsin, United States

Investigational Site Number : 0320009

CABA, Buenos Aires, Argentina

Investigational Site Number : 0320012

Capital Federal, Buenos Aires, Argentina

Investigational Site Number : 0320003

Viedma, Río Negro Province, Argentina

Investigational Site Number : 0320001

Buenos Aires, , Argentina

Investigational Site Number : 0320004

Buenos Aires, , Argentina

Investigational Site Number : 0320014

Córdoba, , Argentina

Investigational Site Number : 0320002

Salta, , Argentina

Investigational Site Number : 0360002

Blacktown, New South Wales, Australia

Investigational Site Number : 0360003

Waratah, New South Wales, Australia

Investigational Site Number : 0360001

Woolloongabba, Queensland, Australia

Investigational Site Number : 0560006

Anderlecht, , Belgium

Investigational Site Number : 0560004

Edegem, , Belgium

Investigational Site Number : 0560005

Ghent, , Belgium

Investigational Site Number : 0560001

Leuven, , Belgium

Investigational Site Number : 0560003

Liège, , Belgium

Investigational Site Number : 0560002

Woluwe-Saint-Lambert, , Belgium

Centro Regional Integrado De Oncologia - CRIO- Site Number : 0760002

Fortaleza, Ceará, Brazil

~Instituto De Oncologia Parana- Site Number : 0760008

Curitiba, Paraná, Brazil

Centro Avancado de Oncologia CECAN - Liga Contra o Cancer- Site Number : 0760026

Natal, Rio Grande do Norte, Brazil

Clínica de Oncologia Reichow Site Number : 0760023

Blumenau, Santa Catarina, Brazil

Hospital de Base Sao Jose do Rio Preto Site Number : 0760001

São José do Rio Preto, São Paulo, Brazil

Hospital Sirio Libanes- Site Number : 0760018

São Paulo, São Paulo, Brazil

Investigational Site Number : 1000008

Burgas, , Bulgaria

Investigational Site Number : 1000010

Pleven, , Bulgaria

Investigational Site Number : 1000007

Plovdiv, , Bulgaria

Investigational Site Number : 1000004

Sofia, , Bulgaria

Investigational Site Number : 1000003

Sofia, , Bulgaria

Investigational Site Number : 1000001

Sofia, , Bulgaria

Investigational Site Number : 1240003

Greenfield Park, Quebec, Canada

Investigational Site Number : 1240010

Montreal, Quebec, Canada

Investigational Site Number : 1520007

Santiago, Reg Metropolitana de Santiago, Chile

Investigational Site Number : 1520006

Santiago, Reg Metropolitana de Santiago, Chile

Investigational Site Number : 1520009

Santiago, Reg Metropolitana de Santiago, Chile

Investigational Site Number : 1520002

Santiago, Reg Metropolitana de Santiago, Chile

Investigational Site Number : 1520001

Viña del Mar, Región de Valparaíso, Chile

Investigational Site Number : 1560026

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 : 1560044

Chongqing, , China

Investigational Site Number : 1560043

Chongqing, , China

Investigational Site Number : 1560024

Fuzhou, , China

Investigational Site Number : 1560001

Guangzhou, , China

Investigational Site Number : 1560036

Guangzhou, , China

Investigational Site Number : 1560037

Guangzhou, , China

Investigational Site Number : 1560017

Guangzhou, , China

Investigational Site Number : 1560025

Hangzhou, , China

Investigational Site Number : 1560033

Hangzhou, , China

Investigational Site Number : 1560021

Hangzhou, , China

Investigational Site Number : 1560011

Hangzhou, , China

Investigational Site Number : 1560005

Harbin, , China

Investigational Site Number : 1560050

Huizhou, , China

Investigational Site Number : 1560047

Jinan, , China

Investigational Site Number : 1560023

Nanjing, , China

Investigational Site Number : 1560019

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 : 1560041

Zhengzhou, , China

Investigational Site Number : 1560040

Zhengzhou, , China

Investigational Site Number : 2500010

Bordeaux, , France

Investigational Site Number : 2500008

Caen, , France

Investigational Site Number : 2500006

Créteil, , France

Investigational Site Number : 2500007

Grenoble, , 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-Bénite, , France

Investigational Site Number : 2500003

Rennes, , France

Investigational Site Number : 2500012

Saint-Herblain, , France

Investigational Site Number : 2500002

Saint-Mandé, , France

Investigational Site Number : 2500004

Villejuif, , France

Investigational Site Number : 2760002

Essen, , Germany

Investigational Site Number : 2760001

Heidelberg, , Germany

Investigational Site Number : 3000005

Athens, , Greece

Investigational Site Number : 3000001

Athens, , Greece

Investigational Site Number : 3000003

Heraklion, , Greece

Investigational Site Number : 3000004

Ioannina, , Greece

Investigational Site Number : 3000006

Thessaloniki, , Greece

Investigational Site Number : 3480003

Budapest, , Hungary

Investigational Site Number : 3480007

Budapest, , Hungary

Investigational Site Number : 3480005

Kaposvár, , Hungary

Investigational Site Number : 3760001

Haifa, , Israel

Investigational Site Number : 3760002

Kfar Saba, , Israel

Investigational Site Number : 3760003

Petah Tikva, , Israel

Investigational Site Number : 3800004

Ravenna, Emilia-Romagna, Italy

Investigational Site Number : 3800005

Rozzano, Milano, Italy

Investigational Site Number : 3800003

Orbassano, Torino, Italy

Investigational Site Number : 3800006

Catania, , Italy

Investigational Site Number : 3800001

Milan, , Italy

Investigational Site Number : 3920002

Nagoya, Aichi-ken, Japan

Investigational Site Number : 3920015

Nagoya, Aichi-ken, Japan

Investigational Site Number : 3920012

Fukuoka, Fukuoka, Japan

Investigational Site Number : 3920008

Kurume-shi, Fukuoka, Japan

Investigational Site Number : 3920016

Sapporo, Hokkaido, Japan

Investigational Site Number : 3920017

Himeji-shi, Hyōgo, Japan

Investigational Site Number : 3920006

Kanazawa, Ishikawa-ken, Japan

Investigational Site Number : 3920005

Yokohama, Kanagawa, Japan

Investigational Site Number : 3920009

Natori-shi, Miyagi, Japan

Investigational Site Number : 3920001

Hirakata-shi, Osaka, Japan

Investigational Site Number : 3920003

Osaka, Osaka, Japan

Investigational Site Number : 3920013

Osaka Sayama-shi, Osaka, Japan

Investigational Site Number : 3920004

Sunto-gun, Shizuoka, Japan

Investigational Site Number : 3920011

Bunkyo-ku, Tokyo, Japan

Investigational Site Number : 3920018

Mitaka-shi, Tokyo, Japan

Investigational Site Number : 3920007

Wakayama, Wakayama, Japan

Investigational Site Number : 3920010

Ube-shi, Yamaguchi, Japan

Investigational Site Number : 4840003

Cuauhtémoc, Mexico City, Mexico

Investigational Site Number : 5280003

's-Hertogenbosch, , Netherlands

Investigational Site Number : 5280004

Breda, , Netherlands

Investigational Site Number : 5280005

Utrecht, , Netherlands

Investigational Site Number : 6160004

Olsztyn, Warmian-Masurian Voivodeship, Poland

Investigational Site Number : 6160001

Warsaw, , Poland

Investigational Site Number : 6200002

Almada, , Portugal

Investigational Site Number : 6200001

Lisbon, , Portugal

Investigational Site Number : 6200004

Lisbon, , Portugal

Investigational Site Number : 6200005

Porto, , Portugal

Investigational Site Number : 6200006

Porto, , Portugal

Investigational Site Number : 6420008

Alba Iulia, , Romania

Investigational Site Number : 6420009

Brasov, , Romania

Investigational Site Number : 6420003

Bucaresti, , Romania

Investigational Site Number : 6420010

Cluj-Napoca, , Romania

Investigational Site Number : 6420011

Cluj-Napoca, , Romania

Investigational Site Number : 6420012

Otopeni, , Romania

Investigational Site Number : 6420005

Timișoara, , Romania

Investigational Site Number : 6430001

Moscow, , Russia

Investigational Site Number : 6430003

Saint Petersburg, , Russia

Investigational Site Number : 7020001

Singapore, , Singapore

Investigational Site Number : 7020002

Singapore, , Singapore

Investigational Site Number : 4100008

Busan, Busan, South Korea

Investigational Site Number : 4100005

Cheongju-si, North Chungcheong, South Korea

Investigational Site Number : 4100006

Seoul, Seoul-teukbyeolsi, South Korea

Investigational Site Number : 4100007

Seoul, Seoul-teukbyeolsi, South Korea

Investigational Site Number : 4100003

Seoul, Seoul-teukbyeolsi, South Korea

Investigational Site Number : 4100004

Seoul, Seoul-teukbyeolsi, South Korea

Investigational Site Number : 4100001

Seoul, , South Korea

Investigational Site Number : 7240007

Barcelona, Barcelona [Barcelona], Spain

Investigational Site Number : 7240005

Barcelona, Barcelona [Barcelona], Spain

Investigational Site Number : 7240001

L'Hospitalet de Llobregat, Barcelona [Barcelona], Spain

Investigational Site Number : 7240009

Madrid / Madrid, Madrid, Comunidad de, Spain

Investigational Site Number : 7240006

Pamplona, Navarre, Spain

Investigational Site Number : 7240002

Madrid, , Spain

Investigational Site Number : 7240004

Málaga, , Spain

Investigational Site Number : 7240011

Seville, , Spain

Investigational Site Number : 7240008

Valencia, , Spain

Investigational Site Number : 7920008

Adana, , Turkey (Türkiye)

Investigational Site Number : 7920012

Adana, , Turkey (Türkiye)

Investigational Site Number : 7920002

Adana, , Turkey (Türkiye)

Investigational Site Number : 7920011

Ankara, , Turkey (Türkiye)

Investigational Site Number : 7920005

Istanbul, , Turkey (Türkiye)

Investigational Site Number : 7920001

Istanbul, , Turkey (Türkiye)

Investigational Site Number : 7920006

Istanbul, , Turkey (Türkiye)

Investigational Site Number : 7920007

Izmir, , Turkey (Türkiye)

Investigational Site Number : 7920010

Izmir, , Turkey (Türkiye)

Investigational Site Number : 7920014

Kocaeli, , Turkey (Türkiye)

Investigational Site Number : 7920009

Malatya, , Turkey (Türkiye)

Countries

United States; Argentina; Australia; Belgium; Brazil; Bulgaria; Canada; Chile; China; France; Germany; Greece; Hungary; Israel; Italy; Japan; Mexico; Netherlands; Poland; Portugal; Romania; Russia; Singapore; South Korea; Spain; Turkey (Türkiye)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1233-0781

Identifier Type: REGISTRY

Identifier Source: secondary_id

2024-515101-26-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

2019-001273-81

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EFC15858

Identifier Type: -

Identifier Source: org_study_id