Epithelial Ovarian Cancer, Fallopian Tube Cancer, Peritoneal Cancer
Conditions
Keywords
Platinum resistant, Folate-receptor alpha expression, Phase 3, Antibody-drug conjugate, mirvetuximab soravtansine, IMGN853, Epithelial Ovarian Cancer, Peritoneal Cancer, Fallopian Tube Cancer, MIRV, FRα
Brief summary
This study is designed to evaluate the efficacy and safety of mirvetuximab soravtansine (MIRV) in participants with platinum-resistant high-grade serous epithelial ovarian cancer, primary peritoneal, or fallopian tube cancer, whose tumors express a high-level of Folate Receptor-Alpha (FRα). Participants will be, in the opinion of the Investigator, appropriate for single-agent therapy for their next line of therapy. All participants will receive single-agent MIRV at 6 mg/kg adjusted ideal body weight administered on Day 1 of every 3-week cycle.
Detailed description
This study is designed to evaluate the efficacy and safety of mirvetuximab soravtansine (MIRV) in participants with platinum-resistant high-grade serous epithelial ovarian cancer, primary peritoneal, or fallopian tube cancer, whose tumors express a high-level of Folate Receptor Alpha (FRα). Participants will be, in the opinion of the Investigator, appropriate for single-agent therapy for their next line of therapy. FRα positivity will be defined by the Ventana FOLR1 (Folate Receptor 1/Folate Receptor Alpha) Assay. Approximately 110 eligible participants will be enrolled to achieve a total of 105 efficacy evaluable participants. Efficacy evaluable participants include those who have measurable lesions per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) at baseline and received at least 1 dose of MIRV. All participants will receive single-agent MIRV at 6 mg/kg adjusted ideal body weight (AIBW) administered on Day 1 of every 3-week cycle (Q3W). Tumor response will be evaluated by the Investigator using RECIST v1.1. Computerized tomography (CT) or magnetic resonance imaging (MRI) scans will be collected for sensitivity analysis by blinded independent central review (BICR). Participants will continue to receive MIRV until disease progression, unacceptable toxicity, withdrawal of consent, death, or until the Sponsor terminates the study (whichever comes first). Tumor assessments, including radiological assessments by CT/MRI scans will be performed at Screening and subsequently every 6 weeks (± 1 week) from Cycle 1 Day 1 (C1D1) for the first 36 weeks then every 12 weeks (± 3 weeks) until disease progression, death, the start of new anticancer therapy, or participant's withdrawal of consent (whichever occurs first). Participants who discontinue MIRV for reasons other than progressive disease (PD) will continue with tumor assessments until documentation of PD or the start of a new anticancer therapy, whichever comes first. Prior to Week 36 (from Cycle 1, Day 1), assessments should occur every 6 weeks (± 1 week) as allowed by local requirements but must occur at an interval of no more than 12 weeks. After Week 36, assessment will occur every 12 weeks (± 3 weeks) until documentation of PD or the start of new anticancer therapy. All participants who discontinue MIRV will be followed for survival every 3 months (± 1 month) until death, lost to follow-up, withdrawal of consent for survival follow-up, or end of study (EOS) (whichever comes first). Additional survival follow-up calls may occur periodically, if needed.
Interventions
DRUGMirvetuximab Soravtansine
Mirvetuximab Soravtansine is an antibody drug conjugate designed to target folate receptor α (FRα). It consists of the humanized anti-FRα mAb M9346A attached via a cleavable disulfide linker to the cytotoxic maytansinoid, DM4.
Sponsors
ImmunoGen, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All participants will receive single-agent MIRV at 6 mg/kg adjusted ideal body weight (AIBW) administered on Day 1 of every 3-week cycle (Q3W)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Female participants ≥ 18 years of age 2. Participants must have a confirmed diagnosis of high-grade serous epithelial ovarian cancer (EOC), primary peritoneal cancer, or fallopian tube cancer 3. Participants must have platinum-resistant disease: 1. Participants who have only had 1 line of platinum based therapy must have received at least 4 cycles of platinum, must have had a response (complete response/remission \[CR\] or partial response/remission \[PR\]) and then progressed between \> 3 months and ≤ 6 months after the date of the last dose of platinum 2. Participants who have received 2 or 3 lines of platinum therapy must have progressed on or within 6 months after the date of the last dose of platinum Note: Progression should be calculated from the date of the last administered dose of platinum therapy to the date of the radiographic imaging showing progression Note: Participants who are platinum refractory during front-line treatment are excluded (see
Exclusion criteria
) 4. Participants must have progressed radiographically on or after their most recent line of anticancer therapy. 5. Participants must be willing to provide an archival tumor tissue block or slides, or undergo procedure to obtain a new biopsy using a low-risk, medically routine procedure for immunohistochemistry (IHC) confirmation of Folate Receptor α (FRα) positivity 6. Participant's tumor must be positive for FRα expression as defined by the Ventana FOLR1 Assay 7. Participants must have at least 1 lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the Investigator) 8. Participants must have received at least 1 but no more than 3 prior systemic lines of anticancer therapy, including at least 1 line of therapy containing bevacizumab, and for whom single-agent therapy is appropriate as the next line of treatment: 1. Adjuvant ± neoadjuvant considered 1 line of therapy 2. Maintenance therapy (e.g., bevacizumab, poly adenosine diphosphate-ribose polymerase (PARP) inhibitors) will be considered part of the preceding line of therapy (i.e., not counted independently) 3. Therapy changed due to toxicity in the absence of progression will be considered part of the same line (i.e., not counted independently) 4. Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance 9. Participants must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 10. Participants must have completed prior therapy within the specified times below: 1. Systemic antineoplastic therapy within 5 half-lives or 4 weeks (whichever is shorter) prior to first dose of MIRV 2. Focal radiation completed at least 2 weeks prior to first dose of MIRV 11. Participants must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia) 12. Participants must have completed any major surgery at least 4 weeks prior to first dose of MIRV and have recovered or stabilized from the side effects of prior surgery 13. Participants must have adequate hematologic, liver and kidney functions defined as: 1. Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (1,500/μL) without G-CSF in the prior 10 days or long-acting WBC growth factors in the prior 20 days 2. Platelet count ≥ 100 x 10\^9/L (100,000/μL) without platelet transfusion in the prior 10 days 3. Hemoglobin ≥ 9.0 g/dL without packed red blood cell (PRBC) transfusion in the prior 21 days 4. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) 5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN 6. Serum bilirubin ≤ 1.5 x ULN (patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin \< 3.0 x ULN) 7. Serum albumin ≥ 2 g/dL 14. Participants or their legally authorized representative must be willing and able to sign the informed consent form (ICF) and to adhere to the protocol requirements 15. Women of childbearing potential (WCBP) must agree to use highly effective contraceptive method(s) while on MIRV and for at least 3 months after the last dose 16. WCBP must have a negative pregnancy test within the 4 days prior to the first dose of MIRV
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR): Percentage of Participants With Objective Response as Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | Up to approximately 15 months | ORR was defined as percentage of participants with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR). CR: Disappearance of all target or non-target lesions. All pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeters (mm). PR: At least 30% decrease in the sum of the longest diameters (SoD) of target lesions, taking as reference the baseline SoD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1 | Up to approximately 15 months | DOR was defined as the time from the date of the first response (CR or PR), until the date of progressive disease (PD) or death from any cause, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. DOR was estimated using the Kaplan-Meier method. |
| Percentage of Participants With CA-125 Confirmed Clinical Response Per Gynecologic Cancer Intergroup (GCIG) Criteria | Up to approximately 15 months | The GCIG CA-125 response was defined as at least 50% reduction in CA-125 levels from baseline. The response must have been confirmed and maintained for at least 28 days. |
| Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1 | Up to approximately 15 months | PFS was defined as the time from initiation of study drug until the date of PD or death whichever occurred first, estimated using the Kaplan-Meier method. PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions and appearance of new lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. |
| Overall Survival Assessed by the Investigator Using RECIST v1.1 | Up to approximately 27 months | Overall survival was defined as the time from the date of first dose until the date of death from any cause, estimated using the Kaplan-Meier method. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to approximately 27 months | An adverse event (AE) was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to study drug. TEAEs were defined as AEs with an onset date on or after the first dose of Study drug, and within 30 days of the last dose of study drug or prior to the start of a new anticancer treatment, whichever occurred first. A summary of all Serious Adverse Events (SAEs) and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
Countries
Australia, Belgium, Bulgaria, Czechia, Germany, Ireland, Israel, Italy, Poland, Spain, United States
Participant flow
Pre-assignment details
Participants were enrolled at 39 sites in North America, Europe, and Asia Pacific.
Participants by arm
| Arm | Count |
|---|---|
| Mirvetuximab Soravtansine Participants received single-agent mirvetuximab soravtansine (MIRV) at 6 mg/kg AIBW administered IV on Day 1 of every 3-week cycle (Q3W). | 106 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 62 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Other than specified | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Mirvetuximab Soravtansine |
|---|---|
| Age, Continuous | 62 years STANDARD_DEVIATION 10 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 99 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 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 | 2 Participants |
| Race (NIH/OMB) White | 102 Participants |
| Sex: Female, Male Female | 106 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 62 / 106 |
| other Total, other adverse events | 102 / 106 |
| serious Total, serious adverse events | 36 / 106 |
Outcome results
Primary
Objective Response Rate (ORR): Percentage of Participants With Objective Response as Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
ORR was defined as percentage of participants with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR). CR: Disappearance of all target or non-target lesions. All pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeters (mm). PR: At least 30% decrease in the sum of the longest diameters (SoD) of target lesions, taking as reference the baseline SoD.
Time frame: Up to approximately 15 months
Population: The investigator (INV) Efficacy Evaluable population was defined as all participants who received at least 1 dose of study drug and who had measurable disease at baseline by investigator assessment per RECIST 1.1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mirvetuximab Soravtansine | Objective Response Rate (ORR): Percentage of Participants With Objective Response as Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 32.4 percentage of participants |
Secondary
Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1
DOR was defined as the time from the date of the first response (CR or PR), until the date of progressive disease (PD) or death from any cause, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. DOR was estimated using the Kaplan-Meier method.
Time frame: Up to approximately 15 months
Population: All participants that showed a CR or PR according to RECIST 1.1 were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mirvetuximab Soravtansine | Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1 | 6.93 months |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to study drug. TEAEs were defined as AEs with an onset date on or after the first dose of Study drug, and within 30 days of the last dose of study drug or prior to the start of a new anticancer treatment, whichever occurred first. A summary of all Serious Adverse Events (SAEs) and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Time frame: Up to approximately 27 months
Population: The Safety population was defined as participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mirvetuximab Soravtansine | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 105 Participants |
Secondary
Overall Survival Assessed by the Investigator Using RECIST v1.1
Overall survival was defined as the time from the date of first dose until the date of death from any cause, estimated using the Kaplan-Meier method.
Time frame: Up to approximately 27 months
Population: INV Efficacy Evaluable population was defined as all participants who received at least 1 dose of study drug and who had measurable disease at baseline by investigator assessment per RECIST 1.1.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mirvetuximab Soravtansine | Overall Survival Assessed by the Investigator Using RECIST v1.1 | 15.0 months |
Secondary
Percentage of Participants With CA-125 Confirmed Clinical Response Per Gynecologic Cancer Intergroup (GCIG) Criteria
The GCIG CA-125 response was defined as at least 50% reduction in CA-125 levels from baseline. The response must have been confirmed and maintained for at least 28 days.
Time frame: Up to approximately 15 months
Population: The CA-125-Evaluable population was defined as all participants who received at least 1 dose of study drug and whose pretreatment sample was ≥2.0 times the upper limit of normal (ULN), within 2 weeks prior to first dose of mirvetuximab soravtansine, and who had at least 1 postbaseline CA-125 evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mirvetuximab Soravtansine | Percentage of Participants With CA-125 Confirmed Clinical Response Per Gynecologic Cancer Intergroup (GCIG) Criteria | 46.5 percentage of participants |
Secondary
Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1
PFS was defined as the time from initiation of study drug until the date of PD or death whichever occurred first, estimated using the Kaplan-Meier method. PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions and appearance of new lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
Time frame: Up to approximately 15 months
Population: INV Efficacy Evaluable population was defined as all participants who received at least 1 dose of study drug and who had measurable disease at baseline by investigator assessment per RECIST 1.1.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mirvetuximab Soravtansine | Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1 | 4.27 months |