Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
NSCLC, MORAb-202, Farletuzumab ecteribulin, Adenocarcinoma
Brief summary
The aim of this study is to characterize the safety and tolerability of MORAb-202, and to assess the objective response rate in participants with previously treated, metastatic NSCLC AC.
Interventions
DRUGMORAb-202
Specified dose on specified days
Sponsors
Eisai Inc.
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
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 documented metastatic NSCLC AC (as defined by the 8th International Association for the Study of Lung Cancer Classification). * Measurable target disease assessed by the investigator according to RECIST 1.1. * Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
Exclusion criteria
* NSCLC histologies other than AC (ie, squamous cell carcinoma, large cell carcinoma). * Significant third-space fluid retention (eg, ascites or pleural effusion) that requires repeated drainage. * Prior pneumonectomy. Prior lobectomy and segmentectomy are allowed \> 12 months before treatment. * Recent chest radiotherapy. Participants with chest or chest wall radiation may be permitted if chest radiation is documented \> 6 months before starting study treatment. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Drug -Related Adverse Events Leading to Discontinuation | From first dose and 30 days after last dose of study therapy (up to approximately 12 months). | An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. |
| Objective Response Rate as Per Investigator | From the date of randomization to the date of first objectively documented progression or death, whichever occurs first (Up to approximately 12 months) | ORR is defined as the percentage of participants whose best overall response (BOR) is either CR or PR per response evaluation criteria in solid tumors (RECIST) v1.1 based on Clopper-Pearson method. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\\< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events and Serious Adverse Events and Adverse Event of Special Interest (AESI) and Deaths and Grade 3/4 Laboratory Abnormalities (SI Units) | From first dose and 30 days after last dose of study therapy (up to approximately 12 months). | An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. Serious adverse events (SAE) are defined as any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Death). |
| Disease Control Rate as Per Investigator | From the date of randomization to the date of first objectively documented progression or death, whichever occurs first (Up to approximately 12 months) | Disease Control Rate (DCR) is defined as the number of randomized participants who achieve a BOR of confirmed CR, confirmed PR, or stable disease (SD) divided by the number of all randomized participants. per response evaluation criteria in solid tumors (RECIST) v1.1 based on Clopper-Pearson method. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\\< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. |
| Duration of Response as Per Investigator | From the date of randomization to the date of first objectively documented progression or death, whichever occurs first (Up to approximately 12 months) | DOR for a participant with a best overall response (BOR) of CR or PR is defined as the time between the date of first response and the date of the first objectively documented tumor progression by investigator per response evaluation criteria in solid tumors (RECIST) v1.1 or death, whichever occurs first. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\\< 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. |
| Progression Free-Survival as Per Investigator | From the date of randomization to the date of first objectively documented progression or death, whichever occurs first (Up to approximately 12 months) | PFS is defined for all randomized participants as the date from randomization to the date of the documentation of disease progression or death due to any cause, whichever is earlier. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest 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 one or more new lesions is also considered progression. |
Countries
Australia, Belgium, Chile, France, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MORAb-202 25mg/m^2 Participants with metastatic non-small cell lung cancer (NSCLC) adenocarcinoma after progression on prior therapies received 25mg/m\^2 intravenous infusion once every 3 weeks (Q3W). | 31 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 6 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | STUDY TERMINATED BY SPONSOR | 16 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | MORAb-202 25mg/m^2 |
|---|---|
| Age, Continuous | 65.4 years STANDARD_DEVIATION 10.37 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 30 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 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 | 30 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 7 / 31 |
| other Total, other adverse events | 29 / 31 |
| serious Total, serious adverse events | 7 / 31 |
Outcome results
Primary
Number of Participants With Drug -Related Adverse Events Leading to Discontinuation
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Time frame: From first dose and 30 days after last dose of study therapy (up to approximately 12 months).
Population: All Treated Participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MORAb-202 25mg/m^2 | Number of Participants With Drug -Related Adverse Events Leading to Discontinuation | 3 Participants |
Primary
Objective Response Rate as Per Investigator
ORR is defined as the percentage of participants whose best overall response (BOR) is either CR or PR per response evaluation criteria in solid tumors (RECIST) v1.1 based on Clopper-Pearson method. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\\< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time frame: From the date of randomization to the date of first objectively documented progression or death, whichever occurs first (Up to approximately 12 months)
Population: All Randomized Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MORAb-202 25mg/m^2 | Objective Response Rate as Per Investigator | 9.7 percentage of participants |
Secondary
Disease Control Rate as Per Investigator
Disease Control Rate (DCR) is defined as the number of randomized participants who achieve a BOR of confirmed CR, confirmed PR, or stable disease (SD) divided by the number of all randomized participants. per response evaluation criteria in solid tumors (RECIST) v1.1 based on Clopper-Pearson method. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\\< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time frame: From the date of randomization to the date of first objectively documented progression or death, whichever occurs first (Up to approximately 12 months)
Population: All Randomized Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MORAb-202 25mg/m^2 | Disease Control Rate as Per Investigator | 67.7 percentage of participants |
Secondary
Duration of Response as Per Investigator
DOR for a participant with a best overall response (BOR) of CR or PR is defined as the time between the date of first response and the date of the first objectively documented tumor progression by investigator per response evaluation criteria in solid tumors (RECIST) v1.1 or death, whichever occurs first. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\\< 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time frame: From the date of randomization to the date of first objectively documented progression or death, whichever occurs first (Up to approximately 12 months)
Population: All Randomized Participants. Only responders (CR or PR) were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MORAb-202 25mg/m^2 | Duration of Response as Per Investigator | NA months |
Secondary
Number of Participants With Adverse Events and Serious Adverse Events and Adverse Event of Special Interest (AESI) and Deaths and Grade 3/4 Laboratory Abnormalities (SI Units)
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. Serious adverse events (SAE) are defined as any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Death).
Time frame: From first dose and 30 days after last dose of study therapy (up to approximately 12 months).
Population: All Treated Participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MORAb-202 25mg/m^2 | Number of Participants With Adverse Events and Serious Adverse Events and Adverse Event of Special Interest (AESI) and Deaths and Grade 3/4 Laboratory Abnormalities (SI Units) | Adverse Events Grade 1 | 10 Participants |
| MORAb-202 25mg/m^2 | Number of Participants With Adverse Events and Serious Adverse Events and Adverse Event of Special Interest (AESI) and Deaths and Grade 3/4 Laboratory Abnormalities (SI Units) | Adverse Events Grade 2 | 5 Participants |
| MORAb-202 25mg/m^2 | Number of Participants With Adverse Events and Serious Adverse Events and Adverse Event of Special Interest (AESI) and Deaths and Grade 3/4 Laboratory Abnormalities (SI Units) | Adverse Events Grade 3 | 3 Participants |
| MORAb-202 25mg/m^2 | Number of Participants With Adverse Events and Serious Adverse Events and Adverse Event of Special Interest (AESI) and Deaths and Grade 3/4 Laboratory Abnormalities (SI Units) | Adverse Events Grade 4 | 0 Participants |
| MORAb-202 25mg/m^2 | Number of Participants With Adverse Events and Serious Adverse Events and Adverse Event of Special Interest (AESI) and Deaths and Grade 3/4 Laboratory Abnormalities (SI Units) | Adverse Events Grade 5 | 0 Participants |
| MORAb-202 25mg/m^2 | Number of Participants With Adverse Events and Serious Adverse Events and Adverse Event of Special Interest (AESI) and Deaths and Grade 3/4 Laboratory Abnormalities (SI Units) | Serious Adverse Events (Any Grade) | 7 Participants |
| MORAb-202 25mg/m^2 | Number of Participants With Adverse Events and Serious Adverse Events and Adverse Event of Special Interest (AESI) and Deaths and Grade 3/4 Laboratory Abnormalities (SI Units) | Serious Adverse Events (Grade 3/4) | 7 Participants |
| MORAb-202 25mg/m^2 | Number of Participants With Adverse Events and Serious Adverse Events and Adverse Event of Special Interest (AESI) and Deaths and Grade 3/4 Laboratory Abnormalities (SI Units) | Serious Adverse Events Grade 5 | 1 Participants |
| MORAb-202 25mg/m^2 | Number of Participants With Adverse Events and Serious Adverse Events and Adverse Event of Special Interest (AESI) and Deaths and Grade 3/4 Laboratory Abnormalities (SI Units) | Drug related SAEs Any Grade | 2 Participants |
| MORAb-202 25mg/m^2 | Number of Participants With Adverse Events and Serious Adverse Events and Adverse Event of Special Interest (AESI) and Deaths and Grade 3/4 Laboratory Abnormalities (SI Units) | Drug related SAEs Grade 3-4 | 2 Participants |
| MORAb-202 25mg/m^2 | Number of Participants With Adverse Events and Serious Adverse Events and Adverse Event of Special Interest (AESI) and Deaths and Grade 3/4 Laboratory Abnormalities (SI Units) | Drug related SAEs Grade 5 | 0 Participants |
| MORAb-202 25mg/m^2 | Number of Participants With Adverse Events and Serious Adverse Events and Adverse Event of Special Interest (AESI) and Deaths and Grade 3/4 Laboratory Abnormalities (SI Units) | Drug related AEs Grade 1 | 10 Participants |
| MORAb-202 25mg/m^2 | Number of Participants With Adverse Events and Serious Adverse Events and Adverse Event of Special Interest (AESI) and Deaths and Grade 3/4 Laboratory Abnormalities (SI Units) | Drug related AEs Grade 2 | 5 Participants |
| MORAb-202 25mg/m^2 | Number of Participants With Adverse Events and Serious Adverse Events and Adverse Event of Special Interest (AESI) and Deaths and Grade 3/4 Laboratory Abnormalities (SI Units) | Drug related AEs Grade 3 | 3 Participants |
| MORAb-202 25mg/m^2 | Number of Participants With Adverse Events and Serious Adverse Events and Adverse Event of Special Interest (AESI) and Deaths and Grade 3/4 Laboratory Abnormalities (SI Units) | Drug related AEs Grade 4 | 0 Participants |
| MORAb-202 25mg/m^2 | Number of Participants With Adverse Events and Serious Adverse Events and Adverse Event of Special Interest (AESI) and Deaths and Grade 3/4 Laboratory Abnormalities (SI Units) | Drug related AEs Grade 5 | 0 Participants |
| MORAb-202 25mg/m^2 | Number of Participants With Adverse Events and Serious Adverse Events and Adverse Event of Special Interest (AESI) and Deaths and Grade 3/4 Laboratory Abnormalities (SI Units) | AESI - Pneumonitis | 2 Participants |
| MORAb-202 25mg/m^2 | Number of Participants With Adverse Events and Serious Adverse Events and Adverse Event of Special Interest (AESI) and Deaths and Grade 3/4 Laboratory Abnormalities (SI Units) | AESI - Bronchospasm | 1 Participants |
| MORAb-202 25mg/m^2 | Number of Participants With Adverse Events and Serious Adverse Events and Adverse Event of Special Interest (AESI) and Deaths and Grade 3/4 Laboratory Abnormalities (SI Units) | Infusion related reaction | 1 Participants |
| MORAb-202 25mg/m^2 | Number of Participants With Adverse Events and Serious Adverse Events and Adverse Event of Special Interest (AESI) and Deaths and Grade 3/4 Laboratory Abnormalities (SI Units) | Deaths | 7 Participants |
| MORAb-202 25mg/m^2 | Number of Participants With Adverse Events and Serious Adverse Events and Adverse Event of Special Interest (AESI) and Deaths and Grade 3/4 Laboratory Abnormalities (SI Units) | Lymphocytes (ABSOLUTE) Grade 3 | 1 Participants |
| MORAb-202 25mg/m^2 | Number of Participants With Adverse Events and Serious Adverse Events and Adverse Event of Special Interest (AESI) and Deaths and Grade 3/4 Laboratory Abnormalities (SI Units) | Creatinine - Grade 3 | 2 Participants |
Secondary
Progression Free-Survival as Per Investigator
PFS is defined for all randomized participants as the date from randomization to the date of the documentation of disease progression or death due to any cause, whichever is earlier. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest 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 one or more new lesions is also considered progression.
Time frame: From the date of randomization to the date of first objectively documented progression or death, whichever occurs first (Up to approximately 12 months)
Population: All Randomized Participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MORAb-202 25mg/m^2 | Progression Free-Survival as Per Investigator | 3.52 months |