MIRASOL: A Randomized, Open-label, Phase 3 Study of Mirvetuximab Soravtansine vs. Investigator's Choice of Chemotherapy in Platinum-Resistant, Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers With High Folate Receptor-Alpha Expression
Objective
This Phase 3 study is designed to compare the efficacy and safety of mirvetuximab soravtansine vs. investigator's choice chemotherapy in patients with platinum-resistant high-grade epithelial ovarian cancer, primary peritoneal, or fallopian tube cancer, whose tumors express a high-level of FRα. Patients will be, in the opinion of the Investigator, appropriate for single-agent therapy for their next line of therapy. Folate receptor alpha (FRα) positivity will be defined by the Ventana FOLR1 (FOLR1-2.1) CDx assay.
Study Arms
- Experimental: mirvetuximab soravtansine (MIRV; IMGN853)
- Active Comparator: Investigator's choice of chemotherapy
Eligibility
- Female patients ≥ 18 years of age
- Patients must have a confirmed diagnosis of high-grade serous epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer
- 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
- 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
- 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 IHC confirmation of FRα positivity
- Patient's tumor must be positive for FRα expression as defined by the Ventana FOLR1 (FOLR-2.1) CDx assay
- Patients must have at least one lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the Investigator)
- 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:
- Adjuvant ± neoadjuvant considered one line of therapy
- Maintenance therapy (eg, bevacizumab, PARP inhibitors) will be considered as part of the preceding line of therapy (ie, not counted independently)
- Therapy changed due to toxicity in the absence of progression will be considered as part of the same line (ie, not counted independently)
- Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance
- Patient must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
- Time from prior therapy:
- Systemic antineoplastic therapy (5 half-lives or 4 weeks, whichever is shorter)
- Focal radiation completed at least 2 weeks prior to first dose of study drug
- Patients must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities
- 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
- Patients must have adequate hematologic, liver and kidney functions defined as:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1,500/μL)
- Platelet count ≥ 100 x 109/L (100,000/μL) without platelet transfusion in the prior 10 days
- Hemoglobin ≥ 9.0 g/dL
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN
- Serum bilirubin ≤ 1.5 x ULN (patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin < 3.0 x ULN
- Serum albumin ≥ 2 g/dL
- 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
- Women of childbearing potential (WCBP) must agree to use highly effective contraceptive method(s) (as defined in Section 5.9.6 in the protocol) while on study drug and for at least 3 months after the last dose of MIRV or at least 6 months after the last dose of paclitaxel, pegylated liposomal doxorubicin, or topotecan
WCBP must have a negative pregnancy test within 4 days prior to the first dose of study drug
