Tusamitamab Ravtansine in NSQ NSCLC Participants With Negative or Moderate CEACAM5 Expression Tumors and High Circulating CEA

Study Overview
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Brief Summary
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This is an open label single group, Phase 2, 1-arm study for treatment to evaluate efficacy, safety, and Pharmacokinetic (PK) of tusamitamab ravtansine in nonsquamous non-small-cell-lung-cancer (NSQ NSCLC) participants with negative or moderate CEACAM5 expression tumors and high circulating carcinoembryonic antigen (CEA). Participants who will be enrolled, will receive tusamitamab ravtansine as monotherapy every two weeks (Q2W) until disease progression, unacceptable adverse event (AE), initiation of a new anticancer therapy, or the participant's or investigator's decision to stop the treatment, whichever comes first. A total of approximately 38 participants are planned to be treated.

Detailed Description
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40 weeks (up to 4 weeks for screening, a median of 24 weeks for treatment, and a median of 12 weeks for end of treatment assessments and the safety follow-up visit).

Official Title
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Open-label, Phase 2 Study, Evaluating the Efficacy and Safety of Tusamitamab Ravtansine in Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC) Participants With Negative or Moderate CEACAM5 Expression Tumors and High Circulating CEA

Conditions
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Non-squamous Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Tusamitamab ravtansine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically proven diagnosis of NSQ NSCLC metastatic disease at study entry; progression after platinum-based chemotherapy and immune checkpoint inhibitor. Participants with moderate or negative CEACAM5 expression as demonstrated prospectively by central laboratory via immune histochemistry (ICH) and high circulating CEA levels (≥100 ng/mL). Moderate CEACAM5 expression is defined as intensity ≥ 2 + in ≥ 1% and <50 % of tumor cells. Negative CEACAM5 expression is defined as intensity of 1 + whatever the percentage of stained tumor cells or <1% of tumor cells. At least one measurable lesion by RECIST v1.1 Eastern Cooperative Oncology Group (ECOG) performance status 0-1. Women of childbearing potential or male patient with women of childbearing potential who agree to use highly effective method of birth control. Exclusion Criteria: Patients with untreated brain metastases or history of leptomeningeal disease. 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. History of known uncontrolled infection with human immunodeficiency virus (HIV), or unresolved viral hepatitis Significant concomitant illness that could impair the participation in the study or interpretation of the results or any major surgery with 3 weeks prior treatment administration Nonresolution of any prior treatment-related toxicity to <Grade 2 according to NCI CTCAE v5.0, with the exception of alopecia, vitiligo, or active thyroiditis controlled with hormone replacement therapy. Previous history of and/or unresolved corneal disorders. The use of contact lenses is not permitted. Prior treatment with maytansinoid derivatives (DM1 or DM4 antibody drug conjugate) or any drug targeting CEACAM5. Concurrent treatment with any other anticancer therapy Poor bone marrow, liver or kidney functions. The above information is not intended to contain all considerations relevant to a patient's 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tusamitamab ravtansine<br>Tusamitamab ravtansine dose will be administered on Day 1 via IV infusion and repeated once every 2 weeks. The duration of 1 cycle will be 14 days (1 administration of tusamitamab ravtansine per cycle). | Drug: Tusamitamab ravtansine<br>* Pharmaceutical Form: Concentrate for solution Route of Administration: Intravenous infusion<br>* Other names: SAR408701;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Objective Response Rate (ORR), defined as the proportion of participants who have a confirmed complete response (CR) or partial response (PR) as best overall response (BOR) per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 | Baseline up to approximately 9 months after last patient treated | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and laboratory abnormalities | Incidence of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and laboratory abnormalities according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 | Baseline up to approximately 90 days after the last study treatment administration | 
| Progression-free survival (PFS) | PFS defined as the time from the date of first tusamitamab ravtansine administration to the date of the first documented disease progression or death due to any cause, whichever comes first. | Baseline up to approximately 9 months after last patient treated | 
| Disease control rate (DCR) | DCR defined as the percentage of participants who have achieved confirmed CR or PR, or stable disease as BOR per RECIST v1.1 | Baseline up to approximately 9 months after last patient treated | 
| Duration of response (DOR) | DOR, defined as the time from first documented evidence of CR or PR until progressive disease (PD) determined per RECIST v1.1 or death from any cause, whichever occurs first | Baseline up to approximately 9 months after last patient treated | 
| Incidence of participants with anti-therapeutic antibodies (ATAs) against tusamitamab ravtansine |  | Baseline up to approximately 30 days after the last study treatment administration |