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

Study Overview
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Brief Summary
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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

Detailed Description
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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).

Official Title
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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

Conditions
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Non-small Cell Lung Cancer Metastatic

Intervention / Treatment
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* Drug: SAR408701
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAR408701 (tusamitamab ravtansine)<br>Administered intravenously once every 2 weeks | Drug: SAR408701<br>* Pharmaceutical form: Concentrate for solution for intravenous infusion Route of administration: intravenous (IV) infusion<br>|
| Active Comparator: Docetaxel<br>Administered intravenously once every 3 weeks | Drug: Docetaxel<br>* Pharmaceutical form: Concentrate for solution for intravenous infusion Route of administration: IV infusion<br>* Other names: TAXOTERE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| Health related quality of life (HRQOL) - physical function | TTD in physical function as determined by EORTC QLQ C30 | Baseline up to median 12 months | 
| Health related quality of life (HRQOL) - role function | TTD in role function as determined by EORTC QLQ C30 | Baseline up to median 12 months | 
| 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) | 
| 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 |