SAR408701 versus docetaxel in previously treated, carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) positive metastatic non-squamous non-small-cell lung cancer patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

21 Aug 2020 → 16 Apr 2026

Decision date (initial)

2024-11-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sanofi-Aventis Recherche & Developpement

External identifiers

EU CT number

2024-515101-26-00

EudraCT number

2019-001273-81

WHO UTN

U1111-1233-0781

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Pharmacodynamic, Efficacy, Safety, Pharmacokinetic

• 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 (progressive 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 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 4

1. To compare the objective response rate (ORR) of tusamitamab ravtansine with docetaxel
2. To compare the health-related quality of life (HRQOL) of tusamitamab ravtansine with docetaxel
3. To evaluate the safety of tusamitamab ravtansine compared to docetaxel
4. To assess the duration of response (DOR) of tusamitamab ravtansine as compared with docetax

Conditions and MedDRA coding

Non-small cell lung cancer metastatic

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. At least 18 years of age or above (or country’s legal age of maturity if above 18 years) and signed the informed consent.
2. Histologically or cytologically proven diagnosis of non-squamous NSCLC with metastatic disease at study entry; progression after platinum-based chemotherapy and immune checkpoint inhibitor.
3. 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).
4. At least one measurable lesion by RECIST v1.1 as determined by local site investigator /radiologist assessment.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
6. 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.
7. 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 12

1. 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.
2. Significant concomitant illnesses, including all severe medical conditions that would impair the patient’s participation in the study or interpretation of the results.
3. 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.
4. 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
5. History of known acquired immunodeficiency syndrome (AIDS) related illnesses or known HIV disease requiring antiretroviral treatment, or unresolved viral hepatitis
6. Previous history of and/or unresolved corneal disorders. The use of contact lenses is not permitted.
7. Concurrent treatment with any other anticancer therapy.
8. Prior treatment with docetaxel or maytansinoid derivatives (DM1 or DM4 antibody drug conjugate) or any drug targeting CEACAM5.
9. Contraindication to use of corticosteroid premedication.
10. 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.
11. Poor bone marrow, liver or kidney functions
12. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Progression free survival (PFS)
2. Overall Survival (OS)

Secondary endpoints 6

1. Objective response rate (ORR)
2. Health related quality of life (HRQOL) - disease related symptoms
3. Health related quality of life (HRQOL) - physical function
4. Health related quality of life (HRQOL) - role function
5. Number of participants with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
6. Duration of response (DOR)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Third parties 5

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications