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 c
Conditions
Interventions
Product Name: mirvetuximab soravtansine
Product Code: IMGN853
Pharmaceutical Form: Concentrate for solution for injection/infusion
INN or Proposed INN: MIRVETUXIMAB SORAVTANSINE
CAS Number: 1453084-3
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: a. Patients who have only had 1 line of platinum based therapy must have received at least 4 cycles of platinum, must have had a response (CR or PR) and then progressed between > 3 months and = 6 months after the date of the last dose of platinum b. Patients 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: Patients who are platinum refractory during front-line treatment are excluded (see exclusion criteria) 4. Patients must have progressed radiographically on or after their most recent line of anticancer therapy 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 FOLRI Assay 7.Patients must have at least 1 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, including at least 1 line of therapy containing bevacizumab, and for whom single-agent therapy is appropriate as the next line of treatment: a.Adjuvant ± neoadjuvant considered 1 line of therapy b.Maintenance therapy (eg, bevacizumab, PARP inhibitors) will be considered 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 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.Patients must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 10.Patients must have completed prior therapy within the specified times below: a.Systemic antineoplastic therapy within 5 half-lives or 4 weeks (whichever is shorter) prior to first dose of mirvetuximab soravtansine b.Focal radiation completed at least 2 weeks prior to first dose of mirvetuximab soravtansine 11.Patients must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia) 12.Patients must have completed any major surgery at least 4 weeks prior to first dose of mirvetuximab soravtansine 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 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 b.Platelet count = 100 x 109/L (100,000/µL) without platelet transfusion in the prior 10 days c. Hemoglobin = 9.0 g/dL without packed red blood cell (PRBC) transfusion in the prior 21 days 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 d
Exclusion criteria
Exclusion criteria: 1.Male patients 2.Patients with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, or low-grade/borderline ovarian tumor 3. Patients with primary platinum-refractory disease, defined as disease that did not respond to (CR or PR) or has progressed within 3 months of the last dose of first-line platinum-containing chemotherapy 4.Patients with prior wide-field radiotherapy (RT) affecting at least 20% of the bone marrow 5.Patients with > Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE) 6.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 7.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.Human immunodeficiency virus (HIV) infection c. Active cytomegalovirus infection d.Any other concurrent infectious disease requiring IV antibiotics within 2 weeks prior to the first dose of mirvetuximab soravtansine Note: testing at screening is not required for the above infections unless clinically indicated 8.Patients with a history of multiple sclerosis (MS) or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome) 9.Patients with clinically significant cardiac disease including, but not limited to, any 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 10.Patients with a history of hemorrhagic or ischemic stroke within 6 months prior to enrollment 11.Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C) 12.Patients with a previous clinical diagnosis of noninfectious interstitial lung disease (ILD), including noninfectious pneumonitis 13.Patients requiring use of folate-containing supplements (eg, folate deficiency) 14.Patients with prior hypersensitivity to monoclonal antibodies (mAb) 15.Women who are pregnant or breastfeeding 16.Patients who received prior treatment with mirvetuximab soravtansine 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 enrollment Note: patients with 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) are eligible 19. Prior known hypersensitivity reactions to study drugs and/or any of their excipients
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To determine the efficacy of mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer (PROC) and high folate receptor alpha (FRa) expression;Secondary Objective: Key Secondary Objective •To determine the durability of response to mirvetuximab soravtansine in patients with PROC and high FRa expression Additional Secondary Objectives •To evaluate the safety and tolerability of mirvetuximab soravtansine •To characterize the clinical activity of mirvetuximab soravtansine in patients with PROC and high FRa expression ;Primary end point(s): •Objective response rate (ORR), which includes best response of complete response (CR) or partial response (PR) as assessed by the Investigator;Timepoint(s) of evaluation of this end point: every 6 weeks from C1DC1 for the first 36 weeks and then 12 weeks thereafter. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Endpoint •Duration of response (DOR), defined as the time from initial Investigator-assessed response (CR or PR) until progressive disease (PD) as assessed by the Investigator Additional Secondary Endpoints •Treatment-emergent adverse events (TEAEs) and laboratory test results, physical examination or vital signs •CA-125 response determined using the GCIG criteria •Progression-free survival (PFS), defined as the time from first dose of mirvetuximab soravtansine until Investigator-assessed radiological PD or death, whichever occurs first •Overall survival (OS), defined as the time from first dose of mirvetuximab soravtansine until death ;Timepoint(s) of evaluation of this end point: Radiologic Tumor Assessments: every 6 weeks for the first 36 weeks and then every 12 weeks thereafter. TEAE: evaluated continually from the start of treatment Laboratory Tests, Physical Exam, Vital Signs: Day 1 of each cycle, end of treatment, and at 30-day follow-up CA-125: Prior to dosing on Day 1 of every cycle | — |
Countries
Australia, Belgium, Bulgaria, Czechia, France, Germany, Ireland, Israel, Italy, Netherlands, Poland, Spain, United States
Contacts
Public ContactPatrick Zweidler-McKay
ImmunoGen, Inc.
Outcome results
None listed