About the study

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

Who can take part?

You may be eligible to participate in the study if you meet the following criteria:

Inclusion criteria

1. Patients ≥ 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 FRα positivity as defined by the Ventana FOLR1 Assay. Patients must be confirmed FRα-high as defined by FRα 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 at study entry (Pre-screening). 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. Patients with homologous recombination deficient-positive tumors who have received prior PARPi plus bevacizumab treatment are eligible.
6. Patients must have relapsed after 1 line (first line) of platinum-based chemotherapy and have platinum-sensitive disease 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 second line (recurrent platinum-sensitive, high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer)
8. Patients must have received no less than 4 and no more than 8 cycles of platinum-based triplet therapy in 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.
9. In the case of interval secondary cytoreductive surgery, patients are permitted to receive only 2 cycles of bevacizumab in combination with the last 3 cycles of platinum-based triplet therapy in the second line. In the case of primary cytoreductive surgery before second-line platinum-based triplet therapy, patients must have no less than 3 cycles of bevacizumab in combination with platinum-based chemotherapy after their surgery and before randomization.
10. Patients will either receive (per investigator's choice), must be receiving, or have received paclitaxel, gemcitabine, or PLD as the partner drug to platinum-based triplet therapy in the second line.
11. Patients must be in CR, PR, or SD, per the investigator, after completion of triplet therapy in second line to be eligible for randomization into the study population. All patients in both populations will have computed tomography (CT)/magnetic resonance imaging (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 triplet therapy in 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 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 either have 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 maintenance treatment and have recovered or stabilized from the side effects of prior surgery before the first dose of maintenance 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 Note: For Run-In patients, these criteria must be met before initiation of triplet therapy and before start of maintenance therapy.
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 maintenance therapy.

Exclusion criteria

1. Patients with endometrioid, clear cell, mucinous, or sarcomatous histology; mixed tumors containing any of the above histologies; or low-grade/borderline ovarian tumor
2. More than one line of prior chemotherapy. Lines of prior anticancer therapy are counted with the following considerations:
3. Neoadjuvant ± adjuvant therapies are considered 1 line of therapy if the neoadjuvant and adjuvant correspond to 1 fully predefined regimen; otherwise, they are counted as 2 prior regimens.
4. Maintenance therapy (eg, bevacizumab, PARPi) will be considered part of the preceding line of therapy (ie, not counted independently).
5. Patients with PD while on or following platinum-based triplet therapy
6. Patients who receive an intervening dose of bevacizumab after the last dose of triplet therapy before randomization
7. Patients with prior wide-field radiotherapy affecting at least 20% of the bone marrow
8. Patients with > Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE)
9. 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
10. Patients with serious concurrent illness or clinically relevant active infection, including but not limited to the following:
11. Active hepatitis B or C infection (whether or not on active antiviral therapy)
12. HIV infection
13. Active cytomegalovirus infection
14. Any other concurrent infectious disease requiring IV antibiotics within 2 weeks before the first dose of maintenance therapy Note: Testing at screening is not required for the above infections unless clinically indicated.
15. Patients with a history of multiple sclerosis or other demyelinating diseases and/or Lambert-Eaton syndrome (paraneoplastic syndrome)
16. Patients with clinically significant cardiac disease including, but not limited to, any of the following:
17. Myocardial infarction ≤ 6 months prior to C1D1 of maintenance treatment
18. Unstable angina pectoris
19. Uncontrolled congestive heart failure (New York Heart Association > class II)
20. Uncontrolled ≥ Grade 3 hypertension (per CTCAE)
21. Uncontrolled cardiac arrhythmias
22. Patients with a history of hemorrhagic or ischemic stroke within 6 months before enrollment
23. Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C)
24. Patients with a previous clinical diagnosis of noninfectious interstitial lung disease, including noninfectious pneumonitis (exception: Grade 1 noninfectious pneumonitis diagnosed on or within 6 weeks after treatment with an immunotherapeutic agent used in the treatment of their malignancy that has resolved per investigator or resolution of the radiologic findings)
25. History of bowel obstruction (including sub-occlusive disease) related to underlying disease within 6 months before the start of maintenance study treatment (triplet therapy for Run-In patients).
26. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess, or evidence of rectosigmoid involvement by pelvic examination, bowel involvement on CT scan, or clinical symptoms of bowel obstruction
27. Clinically significant proteinuria: urine-protein (UPC) ratio ≥ 1.0 or urine dipstick result ≥ 2+; patients with UPC ratio ≥ 1.0 or ≥ 2+ proteinuria should undergo 24-hour urine collection and must show result ≤ 1 g of protein in 24-hour period.
28. History of Grade 4 thromboembolic events
29. Patients requiring use of folate-containing supplements (eg, folate deficiency)
30. Patients with prior hypersensitivity to monoclonal antibodies (mAbs)
31. Women who are pregnant or breastfeeding
32. Patients who received prior treatment with MIRV or other FRα-targeting agents
33. Patients with untreated or symptomatic central nervous system metastases
34. Patients with a history of other malignancy within 3 years before enrollment Note: Patients with tumors with a negligible risk for metastasis or death (eg, controlled basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast) are eligible.
35. Prior known hypersensitivity reactions to study drugs or any of their excipients

For a full list of inclusion/exclusion criteria, please visit ClinicalTrials.gov

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