Non-squamous Non-small Cell Lung Cancer
Conditions
Brief summary
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
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).
Interventions
Pharmaceutical Form: Concentrate for solution Route of Administration: Intravenous infusion
Sponsors
Sanofi
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 46 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | From the first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment, approximately 84 weeks | 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. |
| Progression-Free Survival (PFS) | Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 46 weeks | 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. |
| Disease Control Rate (DCR) | Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 46 weeks | 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. |
| Duration of Response (DOR) | Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 46 weeks | 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. |
Countries
Belgium, France, Italy, Japan, Spain, Turkey (Türkiye), United States
Participant flow
Recruitment details
The study was conducted at 35 investigational sites in 7 countries. A total of 30 participants were screened from 01-Jun-2022 to 01-Dec-2023 of which 8 were screen failures due to not meeting eligibility criteria. The study was terminated as per Sponsor decision and not related to any safety concern.
Pre-assignment details
A total of 22 participants were enrolled in the study. Note: Reason for not completed = Reason for permanent full study intervention discontinuation.
Participants by arm
| Arm | Count |
|---|---|
| Tusamitamab Ravtansine 100 mg/m^2 Participants received tusamitamab ravtansine 100 mg/m\^2 via IV infusion Q2W until disease progression, unacceptable AE, death, initiation of a new anticancer therapy, or the participant's or investigator's decision to stop the treatment. | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse event not related to Coronavirus Disease 2019 | 2 |
| Overall Study | Not related to Coronavirus Disease 2019 | 2 |
| Overall Study | Progressive disease | 18 |
Baseline characteristics
| Characteristic | Tusamitamab Ravtansine 100 mg/m^2 |
|---|---|
| Age, Continuous | 63.5 years STANDARD_DEVIATION 10.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 17 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 13 / 22 |
| other Total, other adverse events | 18 / 22 |
| serious Total, serious adverse events | 7 / 22 |
Outcome results
Primary
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
Population: All-treated population included all enrolled participants exposed to the study treatment, regardless of the amount of treatment administered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tusamitamab Ravtansine 100 mg/m^2 | Objective Response Rate (ORR) | 9.1 percentage of participants |
Secondary
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
Population: All-treated population included all enrolled participants exposed to the study treatment, regardless of the amount of treatment administered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tusamitamab Ravtansine 100 mg/m^2 | Disease Control Rate (DCR) | 36.4 percentage of participants |
Secondary
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
Population: All-treated population included all enrolled participants exposed to the study treatment, regardless of the amount of treatment administered. Only responders (those participants with confirmed CR or PR) were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tusamitamab Ravtansine 100 mg/m^2 | Duration of Response (DOR) | NA months |
Secondary
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
Population: All-treated population included all enrolled participants exposed to the study treatment, regardless of the amount of treatment administered.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tusamitamab Ravtansine 100 mg/m^2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAEs | 21 Participants |
| Tusamitamab Ravtansine 100 mg/m^2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAEs | 7 Participants |
Secondary
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
Population: All-treated population included all enrolled participants exposed to the study treatment, regardless of the amount of treatment administered.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tusamitamab Ravtansine 100 mg/m^2 | Progression-Free Survival (PFS) | 1.87 months |