Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers with High Folate Receptor-Alpha Expression MedDRA version: 21.0 Level: PT Classification code 10061269 Term: Malignant peritoneal neoplasm System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10061328 Term: Ovarian epithelial cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl
Conditions
Interventions
Product Name: mirvetuximab soravtansine
Product Code: IMGN853
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: MIRVETUXIMAB SORAVTANSINE
CAS Number: 1453084-37-1
Current
Sponsors
ImmunoGen, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female patients = 18 years of age 2. Patients must have a confirmed diagnosis of high-grade serous EOC, primary peritoneal cancer, or fallopian tube cancer 3. Patients must have platinum-resistant disease (defined as progression within 6 months from completion of a minimum of four cycles of platinum-containing therapy) Note: This should be calculated from the date of the last administered dose of platinum therapy to the date of the radiographic imaging showing progression.; Patients who are platinum-refractory during front-line treatment are excluded (see exclusion criteria) 4. Patients must have progressed on or after their most recent line of therapy Note: Progression must be determined radiographically and/or by CA-125 GCIG progression criteria 5. Patients 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 FRa positivity 6. Patient's tumor must be positive for FRa expression as defined by the Ventana FOLR1 (FOLR-2.1) CDx assay 7. Patients must have at least one lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the Investigator) 8. Patients must have received at least 1 but no more than 3 prior systemic lines of anticancer therapy, and for whom single-agent therapy is appropriate as the next line of treatment: a. Adjuvant ± neoadjuvant considered one line of therapy b. Maintenance therapy (eg, bevacizumab, PARP inhibitors) will be considered as part of the preceding line of therapy (ie, not counted independently) c. Therapy changed due to toxicity in the absence of progression will be considered as part of the same line (ie, not counted independently) d. Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance. 9. Patient must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 10. Time from prior therapy: a. Systemic antineoplastic therapy (5 half-lives or 4 weeks, whichever is shorter) b. Focal radiation completed at least 2 weeks prior to first dose of study drug 11. Patients must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities 12. Major surgery must be completed at least 4 weeks prior to first dose and have recovered or stabilized from the side effects of prior surgery 13. Patients must have adequate hematologic, liver and kidney functions defined as: a. Absolute neutrophil count (ANC) = 1.5 x 109/L (1,500/µL) b. Platelet count = 100 x 109/L (100,000/µL) without platelet transfusion in the prior 10 days c. Hemoglobin = 9.0 g/dL d. Serum creatinine = 1.5 x upper limit of normal (ULN) e. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3.0 x ULN f. Serum bilirubin = 1.5 x ULN (patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin < 3.0 x ULN) g. Serum albumin = 2 g/dL 14. Patients 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) in while on study drug and for at least 3 months after the last dose of mirvetuximab soravtansine or at least 6 months after the last dose of Pac, PLD, or Topo 16. WCBP must have a
Exclusion criteria
Exclusion criteria: 1. Patients with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, or lowgrade or borderline ovarian tumor 2. Patients with primary platinum-refractory disease, defined as disease that did not respond to or has progressed within 3 months of the last dose of first line platinum-containing chemotherapy 3. Patients with prior wide-field radiotherapy (RT) affecting at least 20% of the bone marrow 4. Patients with > Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE) 5. Patients with active or chronic corneal disorders, history of corneal transplantation, or active ocular conditions requiring ongoing treatment/monitoring such as uncontrolled glaucoma, wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, macular degeneration, presence of papilledema, and /or monocular vision 6. Patients with serious concurrent illness or clinically relevant active infection, including, but not limited to the following: a. Active hepatitis B or C infection (whether or not on active antiviral therapy) b. HIV infection c. Cytomegalovirus infection d. Any other concurrent infectious disease requiring IV antibiotics within 2 weeks before starting study drug 7. Patients with history of multiple sclerosis or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome) 8. Patients with clinically significant cardiac disease including, but not limited to, any one of the following: a. Myocardial infarction = 6 months prior to first dose b. Unstable angina pectoris c. Uncontrolled congestive heart failure (New York Heart Association > class II) d. Uncontrolled = Grade 3 hypertension (per CTCAE) e. Uncontrolled cardiac arrhythmias 9. Patients assigned to PLD stratum only: • Left ventricular ejection fraction (LVEF) below the institutional limit of normal as measured by echocardiography (ECHO) or multigated acquisition (MUGA) scan 10. Patients with a history of hemorrhagic or ischemic stroke within six months prior to randomization 11. Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C) 12. Patients with a previous clinical diagnosis of non-infectious interstitial lung disease (ILD), including noninfectious pneumonitis 13. Patients with required use of folate-containing supplements (eg, folate deficiency) 14. Patients with prior hypersensitivity to monoclonal antibodies 15. Women who are pregnant or lactating 16. Patients with prior treatment with MIRV or other FRa-targeting agents 17. Patients with untreated or symptomatic central nervous system (CNS) metastases 18. Patients with a history of other malignancy within 3 years prior to randomization Note: does not include tumors with a negligible risk for metastasis or death (eg, adequately controlled basal-cell carcinoma or squamous-cell carcinoma of the skin, or carcinoma in situ of the cervix or breast)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the progression-free survival (PFS) of patients randomized to mirvetuximab soravtansine vs. Investigator's choice (IC) of chemotherapy;Secondary Objective: • To compare the objective response rate (ORR) of patients randomized to mirvetuximab soravtansine vs. IC Chemotherapy • To compare overall survival (OS) of patients randomized to mirvetuximab soravtansine vs. IC Chemotherapy • To compare the primary patient-reported outcome (PRO) using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-OV28 (Abdominal/GI Symptom Scale) assessment from patients randomized to mirvetuximab soravtansine vs. IC Chemotherapy;Primary end point(s): PFS, defined as the time from date of randomization until Investigator-assessed progressive disease (PD) or death, whichever occurs first. Results will be summarized by arm - Kaplan-Meier method for survival function estimate - Stratified Cox proportional hazard regression for hazard ratio (HR) estimate - Stratified log-rank test for hypothesis testing;Timepoint(s) of evaluation of this end point: Radiologic Tumor Evaluation: Every 6 weeks (± 1 week) for the first 36 weeks and every 12 weeks (± 1 week) thereafter. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Objective response includes best response of complete response (CR) or partial response (PR) as assessed by the Investigator - Stratified Cochran-Mantel-Haenszel (CMH) test for treatment comparison - Clopper-Pearson method for 95% CI estimation OS defined as the time from date of randomization until the date of death. Patients alive at the time of analysis will be censored at the last known date known to be alive - Kaplan-Meier method for survival function estimate - Stratified Cox proportional hazard regression for HR estimate - Stratified log-rank test for hypothesis testing Primary PRO assessment, defined as the number of patients achieving at least 15 point absolute improvement at Week 8 or Week 9 in the abdominal/GI scale of EORTC QLQ-OV28;Timepoint(s) of evaluation of this end point: Radiologic Tumor Evaluation: Every 6 weeks (± 1 week) for the first 36 weeks and every 12 weeks (± 1 week) thereafter. PRO assessment: screening, every 9 (± 1) weeks from cycle 1, Day 1 until disease progression (per investigator), end of treatment (EOT) and every 3 months (± 1 month) from EOT | — |
Countries
Australia, Belgium, Bulgaria, Canada, Czech Republic, France, Germany, Israel, Italy, Korea, Democratic People's Republic of, Netherlands, Poland, Portugal, Russian Federation, Serbia, Spain, Taiwan, Ukraine, United Kingdom, United States
Contacts
Public ContactPatrick Zweidler-McKay
ImmunoGen, Inc.
Outcome results
None listed