Summary

GLORIOSA is a Phase 3 multicenter, open label study designed to evaluate the safety and
efficacy of mirvetuximab Soravtansine as maintenance therapy in participants with
platinum-sensitive ovarian, primary peritoneal or fallopian tube cancers with high folate
receptor-alpha (FRa) expression.

Objectives

Mirvetuximab Soravtansine (MIRV) is an investigational antibody drug conjugate designed
to selectively kill cancer cells. The antibody (protein) part of MIRV targets tumors by
delivering a cell-killing drug to the tumor cells carrying a tumor-associated protein
called folate receptor alpha (FRa). It is being developed as maintenance therapy for the
treatment of subjects with recurrent platinum-sensitive, highgrade epithelial ovarian,
primary peritoneal, or fallopian tube cancers with high folate receptor-alpha expression.
Patients must have confirmation of FRa positivity by the Ventana FOLR1 Assay.

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Eligibility

1. Patients must be = 18 years of age
2. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
3. Patients must have a confirmed diagnosis of high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer.
4. Patients must be willing to provide an archival tumor tissue block or slides, or must undergo a procedure to obtain a new biopsy using a low-risk, medically routine procedure for IHC confirmation of high FRa expression (reported as "positive") as defined by the Ventana FOLR1 Assay. Patients must be confirmed FRa-high as defined by FRa positivity of = 75% of tumor membrane staining at = 2+ intensity (PS2+) for entry into the study.
5. Prior BRCA testing on the tumor or prior germline testing is required for eligibility. If not done prior, tumor or germline testing will need to be done before study entry. Somatic and germline BRCA-positive patients must have received prior treatment with a PARPi in maintenance following first-line treatment. Note: Local tumor or germline BRCA testing will be acceptable for stratification. If the patient has not been tested, recommend archival tumor samples to be assessed for tissue BRCA. All patients who have received prior first line PARPi maintenance and/or bevacizumab are eligible.
6. Patients' disease must have relapsed after 1 line (first line) of platinum-based chemotherapy and must be platinum-sensitive defined as progression greater than 6 months from last dose of primary platinum therapy.
7. Patients must be appropriate for, currently be on, or have completed platinum-based triplet therapy in the second line (recurrent PSOC).
8. After completion of triplet therapy and before randomization, patients must have received no less than 4 and no greater than 8 cycles of platinum-based triplet therapy in the second line, to include no less than 3 cycles of bevacizumab in combination with platinum-based chemotherapy. If the number of cycles received is less than 6 due to toxicity, this must be documented and toxicity assessed as unlikely related to bevacizumab. Note: A minimum of 4 cycles of combination chemotherapy is required. If carboplatin, paclitaxel, gemcitabine, or pegylated liposomal doxorubicin (PLD) is stopped due to toxicity, up to 4 additional cycles of single agent in combination with bevacizumab is acceptable if appropriately documented.
9. After completion of triplet therapy and before randomization: In the case of interval secondary cytoreductive surgery, patients are permitted to have received only 2 cycles of bevacizumab if given in combination with the last 3 cycles of platinum-based triplet therapy in the second line. In the case of primary cytoreductive surgery before secondline platinum-based triplet therapy, patients must have received no fewer than 3 cycles of bevacizumab in combination with platinum-based chemotherapy after their surgery and before randomization.
10. Patients either will receive (per investigator's choice), must be receiving, or have received paclitaxel, gemcitabine, or pegylated liposomal doxorubicin as the partner drug to platinum-based triplet therapy in the second line.
11. After completion of triplet therapy and before randomization, patients must have achieved a CR, PR, or SD, per the investigator, in the second line to be eligible for randomization into the study population. All patients will have CT or MRI scans and CA-125 measurements at least 3 weeks but no more than 8 weeks after their last planned dose of triplet therapy and before randomization.
12. Patients must be randomized no later than 8 weeks from the last dose of platinum-based triplet therapy in the second line.
13. After completion of triplet therapy and before randomization, patients must meet one of the following criteria:
14. Have at least 1 lesion that meets the definition of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (radiologically measured by the investigator), and determined by the investigator to either have SD or a PR to their treatment; or
15. Have persistently elevated CA-125 without measurable disease and determined by the investigator to have either SD or a PR to their treatment; or
16. Have clinically no evidence of disease by both radiographic interpretation by the investigator and normalization of their CA-125, determined to be a CR.
17. Patients must have stabilized or recovered (to Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia).
18. Patients must have completed any major surgery at least 4 weeks before the first dose of study treatment (either Run-In or maintenance therapy) and have recovered or stabilized from the side effects of prior surgery before the first dose of treatment on study.
19. Patients must have adequate hematologic, liver, and kidney functions defined as follows:
20. Absolute neutrophil count (ANC) = 1.5 × 109/L (1500/µL) without granulocyte colony-stimulating factor in the prior 10 days or long-acting white blood cell (WBC) growth factors in the prior 10 days of C1D1 of maintenance treatment.
21. Platelet count = 100 × 109/L (100,000/µL) without platelet transfusion in the prior 10 days of C1D1 of maintenance treatment
22. Hemoglobin = 9.0 g/dL without packed red blood cell (PRBC) transfusion in the prior 10 days of C1D1 of maintenance treatment
23. Serum creatinine = 1.5 × upper limit of normal (ULN)
24. Aspartate aminotransferase and alanine aminotransferase = 3.0 × ULN
25. Serum bilirubin = 1.5 × ULN (patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin < 3.0 × ULN)
26. Serum albumin = 2 g/dL
27. Patients must be willing and able to sign the informed consent form (ICF) and to adhere to the protocol requirements.
28. Females of childbearing potential (FCBP) must agree to use highly effective contraceptive method(s) (as defined in Section 5.10.7) while on study medication and for at least 3 months after the last dose.
29. FCBP must have a negative pregnancy test within 4 days before the first dose of therapy.

Treatment Sites in Georgia