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

Phase 2TerminatedNCT05245071

Sanofi22 enrolled

Overview

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.

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).

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Non-squamous Non-small Cell Lung Cancer

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (35)

Roswell Park Cancer Institute Site Number : 8400004

Buffalo, New York, United States

Renovatio Clinical Site Number : 8400003

El Paso, Texas, United States

Investigational Site Number : 0560003

Edegem, Belgium

Investigational Site Number : 0560001

Leuven, Belgium

Investigational Site Number : 0560002

Liège, Belgium

Outcomes

Primary Outcomes

Objective Response Rate (ORR)

The ORR was defined as percentage of participants with confirmed complete response (CR) or partial response (PR) as best overall response (BOR) determined per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. The CR was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeters (mm). The PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

Time frame: Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 46 weeks

Secondary Outcomes

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death or was life-threatening or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent disability/incapacity or congenital anomaly/birth defect or was a suspected transmission of any infectious agent via an authorized medicinal product. TEAE was defined as AEs that developed, worsened, or became serious during the treatment-emergent period.

Time frame: From the first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment, approximately 84 weeks

Progression-Free Survival (PFS)

The PFS was defined as the time from the first study treatment administration to the date of the first documented progressive disease (PD) or death due to any cause, whichever came first as per RECIST v1.1. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions was also considered progression.

Time frame: Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 46 weeks

Disease Control Rate (DCR)

The DCR was defined as the percentage of participants who achieved confirmed CR, PR or stable disease (SD) as BOR as per RECIST v1.1. The CR was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. The PR was defined as at least a 30%decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage from the baseline study to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on the study.

Time frame: Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 46 weeks

Duration of Response (DOR)

The DOR was defined as the time from first documented evidence of CR or PR until PD determined per RECIST v1.1 or death from any cause, whichever occurred first. The CR was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. The PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

Time frame: Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 46 weeks