Mirvetuximab Soravtansine With Bevacizumab Versus Bevacizumab as Maintenance in Platinum-sensitive Ovarian, Fallopian Tube, or Peritoneal Cancer

Inclusion Criteria:

1. Patients must be ≥ 18 years of age

2. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance statusof 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, ormust undergo a procedure to obtain a new biopsy using a low-risk, medically routineprocedure for IHC confirmation of high FRα expression (reported as "positive") asdefined by the Ventana FOLR1 Assay. Patients must be confirmed FRα-high as definedby FRα positivity of ≥ 75% of tumor membrane staining at ≥ 2+ intensity (PS2+) forentry into the study.

5. Prior BRCA testing on the tumor or prior germline testing is required foreligibility. If not done prior, tumor or germline testing will need to be donebefore study entry. Somatic and germline BRCA-positive patients must have receivedprior treatment with a PARPi in maintenance following first-line treatment. Note: Local tumor or germline BRCA testing will be acceptable for stratification. Ifthe patient has not been tested, recommend archival tumor samples to be assessed fortissue BRCA. All patients who have received prior first line PARPi maintenanceand/or bevacizumab are eligible.

6. Patients' disease must have relapsed after 1 line (first line) of platinum basedchemotherapy and must be platinum-sensitive defined as progression greater than 6months from last dose of primary platinum therapy.

7. Patients must be appropriate for, currently be on, or have completed platinum-basedtriplet therapy in the second line (recurrent PSOC).

8. After completion of triplet therapy and before randomization, patients must havereceived no less than 4 and no greater than 8 cycles of platinum-based triplettherapy in the second line, to include no less than 3 cycles of bevacizumab incombination with platinum-based chemotherapy. If the number of cycles received isless than 6 due to toxicity, this must be documented and toxicity assessed asunlikely 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 totoxicity, up to 4 additional cycles of single agent in combination with bevacizumabis acceptable if appropriately documented.

9. After completion of triplet therapy and before randomization: In the case ofinterval secondary cytoreductive surgery, patients are permitted to have receivedonly 2 cycles of bevacizumab if given in combination with the last 3 cycles ofplatinum-based triplet therapy in the second line. In the case of primarycytoreductive surgery before secondline platinum-based triplet therapy, patientsmust have received no fewer than 3 cycles of bevacizumab in combination withplatinum-based chemotherapy after their surgery and before randomization.

10. Patients either will receive (per investigator's choice), must be receiving, or havereceived paclitaxel, gemcitabine, or pegylated liposomal doxorubicin as the partnerdrug to platinum-based triplet therapy in the second line.

11. After completion of triplet therapy and before randomization, patients must haveachieved a CR, PR, or SD, per the investigator, in the second line to be eligiblefor randomization into the study population. All patients will have CT or MRI scansand CA-125 measurements at least 3 weeks but no more than 8 weeks after their lastplanned dose of triplet therapy and before randomization.

12. Patients must be randomized no later than 8 weeks from the last dose ofplatinum-based triplet therapy in the second line.

13. After completion of triplet therapy and before randomization, patients must meet oneof the following criteria:

14. Have at least 1 lesion that meets the definition of measurable disease byResponse Evaluation Criteria in Solid Tumors (RECIST) v1.1 (radiologicallymeasured by the investigator), and determined by the investigator to eitherhave SD or a PR to their treatment; or

15. Have persistently elevated CA-125 without measurable disease and determined bythe investigator to have either SD or a PR to their treatment; or

16. Have clinically no evidence of disease by both radiographic interpretation bythe 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 priortherapy-related toxicities (except alopecia).

18. Patients must have completed any major surgery at least 4 weeks before the firstdose of study treatment (either Run-In or maintenance therapy) and have recovered orstabilized from the side effects of prior surgery before the first dose of treatmenton study.

19. Patients must have adequate hematologic, liver, and kidney functions defined asfollows:

20. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (1500/μL) without granulocytecolony-stimulating factor in the prior 10 days or longacting 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 theprior 10 days of C1D1 of maintenance treatment

22. Hemoglobin ≥ 9.0 g/dL without packed red blood cell (PRBC) transfusion in theprior 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 Gilbertsyndrome 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 toadhere to the protocol requirements.

28. Females of childbearing potential (FCBP) must agree to use highly effectivecontraceptive method(s) (as defined in Section 5.10.7) while on study medication andfor at least 3 months after the last dose.

29. FCBP must have a negative pregnancy test within 4 days before the first dose oftherapy.

Exclusion Criteria:

1. Patients with endometrioid, clear cell, mucinous, or sarcomatous histology; mixedtumors containing any of the above histologies; or lowgrade/borderline ovarian tumor

2. More than one line of prior chemotherapy before current/planned triplet therapy.Lines of prior anticancer therapy are counted with the following considerations:

3. Neoadjuvant ± adjuvant therapies are considered 1 line of therapy if theneoadjuvant 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 thepreceding line of therapy (ie, not counted independently).

5. Change due to toxicity will be considered part of the proceeding line oftherapy.

6. Patients with PD while on or following platinum-based triplet therapy

7. After completion of triplet therapy and prior to randomization: Patients who receivean intervening dose of bevacizumab after the last dose of triplet therapy beforerandomization

8. Patients with prior wide-field radiotherapy affecting at least 20% of the bonemarrow

9. Patients with > Grade 1 peripheral neuropathy per Common Terminology Criteria forAdverse Events (CTCAE)

10. Patients with active or chronic corneal disorders, history of cornealtransplantation, or active ocular conditions requiring ongoing treatment/monitoring,such as uncontrolled glaucoma, wet age-related macular degeneration requiringintravitreal injections, active diabetic retinopathy with macular edema, maculardegeneration, presence of papilledema, and/or monocular vision

11. Patients with serious concurrent illness or clinically relevant active infection,including but not limited to the following:

12. Active hepatitis B or C infection (whether or not on active antiviral therapy)

13. HIV infection

14. Active cytomegalovirus infection

15. Any other concurrent infectious disease requiring intravenous (IV) antibioticswithin 2 weeks before the first dose of maintenance therapy Note: Testing atscreening is not required for the above infections unless clinically indicated.

16. Patients with a history of multiple sclerosis or other demyelinating diseases and/orLambert-Eaton syndrome (paraneoplastic syndrome)

17. Patients with clinically significant cardiac disease including, but not limited to,any of the following:

18. Myocardial infarction ≤ 6 months prior to C1D1 of maintenance treatment

19. Unstable angina pectoris

20. Uncontrolled congestive heart failure (New York Heart Association > class II)

21. Uncontrolled ≥ Grade 3 hypertension (per CTCAE)

22. Uncontrolled cardiac arrhythmias

23. Patients with a history of hemorrhagic or ischemic stroke within 6 months beforeenrollment

24. Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C)

25. Patients with a previous clinical diagnosis of noninfectious interstitial lungdisease, including noninfectious pneumonitis (exception: Grade 1 noninfectiouspneumonitis diagnosed on or within 6 weeks after treatment with an immunotherapeuticagent used in the treatment of their malignancy that has resolved per investigatoror resolution of the radiologic findings)

26. History of bowel obstruction (including sub-occlusive disease) related to underlyingdisease within 6 months before the start of maintenance study treatment (triplettherapy for Run-In patients).

27. History of abdominal fistula or gastrointestinal perforation

28. Intra-abdominal abscess, evidence of rectosigmoid involvement by pelvic examination,bowel involvement on CT scan, or clinical symptoms of bowel obstruction within 4weeks prior to randomization (or within 4 weeks prior to starting triplet therapyfor Run- In patients)

29. Clinically significant proteinuria: urine-protein to creatinine (UPC) ratio ≥ 1.0 orurine dipstick result ≥ 2+; patients with UPC ratio ≥ 1.0 or ≥ 2+ proteinuria shouldundergo 24-hour urine collection and must show result ≤ 1 g of protein in a 24-hourperiod.

30. History of Grade 4 thromboembolic events

31. Patients not appropriate for bevacizumab 15 mg/kg dosing at the start of maintenancetherapy as per the treating physician

32. Patients requiring use of folate-containing supplements (eg, folate deficiency)

33. Patients with prior hypersensitivity to monoclonal antibodies (mAbs)

34. Women who are pregnant or breastfeeding

35. Patients who received prior treatment with MIRV or other FRα-targeting agents

36. Patients with untreated or symptomatic central nervous system metastases

37. Patients with a history of other malignancy within 3 years prior to signing studyconsent Note: Patients with tumors with a negligible risk for metastasis or death (eg, controlled basal cell carcinoma or squamous cell carcinoma of the skin, orcarcinoma in situ of the cervix or breast) are eligible.

38. Prior known hypersensitivity reactions to study drugs or any of their excipients