An Evaluation of Maintenance Therapy Combination Mirvetuximab Soravtansine and Olaparib

Inclusion Criteria:

• Provision to sign and date the consent form

• Stated willingness to comply with all study procedures and be available for theduration of the study

• Be a woman aged ≥18 years of age

• Patients must have an Eastern Cooperative Oncology Group Performance Status (ECOGPS) of 0 or 1

• Patients must have a confirmed diagnosis of high-grade serous or endometrioid EOC,primary peritoneal cancer, or fallopian tube cancer

• Patients must have platinum-sensitive disease defined as radiographic progressiongreater than 6 months from last dose of prior platinum therapy (not inclusive ofcurrent/most recent platinum therapy)

• Patients must have had documented complete or partial response, or stable disease,as defined by RECIST 1.1, from last line of platinum therapy

• Patients must have available archival tissue block or slides to confirm FRalphapositivity

• Patients' tumor must have FRalpha high or medium expression

• Prior anticancer therapy:

• Patients must have received at least one prior platinum-based chemotherapyregimen for platinum sensitive recurrent disease.

• Most recent prior chemotherapy regimen must have consisted of at least 4completed cycles and no more than 8 completed cycles

• Most recent prior chemotherapy regimen must have been platinum based

• Patients must have had testing for BRCA mutation (tumor or germline) and, ifpositive, must have received a prior PARP inhibitor as either treatment ormaintenance therapy

• Neoadjuvant +/- adjuvant therapies are considered 1 line of therapy

• Maintenance therapy (eg, Bevacizumab, PARP inhibitors) will be considered partof preceding line of therapy (ie, not counted independently)

• Therapy changed due to toxicity in the absence of progression will beconsidered part of the same line (ie, not counted independently)

• Hormonal therapy will be counted as a separate line of therapy unless it wasgiven as maintenance

• Prior Bevacizumab use is allowed, but concurrent use with study combination isprohibited.

• Cycle 1 Day 1 of trial therapy must be within 8 weeks of last dose of previouschemotherapy.

• Patients must have adequate hematologic, liver, and kidney function as defined as:

• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1500/µL)

• Platelet count ≥ 100 x 109/L (100,000 µL)

• Hemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days

• Serum creatinine ≤ 1.5 x upper limit of normal (ULN)

• Patients must have creatinine clearance estimated of ≥51 mL/min using theCockcroft-Gault equation or based on a 24 hour urine test

• Aspartate aminotransferase (AST)(Serum Glutamic Oxaloacetic Transaminase (SGOT)) and alanine aminotransferase (ALT) (Serum Glutamic PyruvateTransaminase (SGPT)) ≤ 2.5 x ULN unless liver metastases are present in whichcase they must be ≤ 5x ULN

• Serum bilirubin ≤ 1.5 x ULN (patients with documented diagnosis of Gilbertsyndrome are eligible if total bilirubin < 3.0 x ULN)

• Serum albumin ≥ 2 g/dL

Exclusion Criteria:

• Patients with clear cell, mucinous, sarcomatous, low grade/borderline, germ cell, orsex-cord stromal type ovarian tumor

• Patients who have progressed through most recent chemotherapy regimen. Stabledisease (SD) is permissible.

• Patients receiving any systemic chemotherapy or radiotherapy (except for palliativereasons) within 3 weeks prior to study treatment

• Patients with active or chronic corneal disorders, history of cornealtransplantation, or active ocular conditions require 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

• Patients with myelodysplastic syndrome/acute myeloid leukemia or with featuressuggestive of MDS/AML.

• Patients considered a poor medical risk due to a serious, uncontrolled medicaldisorder, non-malignant systemic disease or active, uncontrolled infection. Examplesinclude, but are not limited to:

• Uncontrolled major seizure disorder

• Unstable spinal cord compression

• Any psychiatric disorder that prohibits obtaining informed consent.

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

• Immunocompromised patients, e.g., patient who are known to be serologicallypositive for human immunodeficient virus(HIV)

• Active cytomegalovirus infection

• Any other concurrent infectious disease requiring IV antibiotics within 2 weeksprior to the first dose of MIRV

• Patients with a history of multiple sclerosis (MS) or other demyelinating diseaseand/or Lambert-Eaton syndrome (paraneoplastic syndrome)

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

• Myocardial infarction ≤ 6 months prior to first dose

• Uncontrolled ventricular arrhythmia, recent (within 3 months)

• Superior vena cava syndrome

• Unstable angina pectoris

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

• Uncontrolled ≥ Grade 3 hypertension (per CTCAE)

• Uncontrolled cardiac arrhythmias

• Patients with a history of hemorrhagic or ischemic stroke within 6 months prior toenrollment

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

• Patients with a previous clinical diagnosis of noninfectious interstitial lungdisease (ILD) or Extensive interstitial bilateral lung disease on High ResolutionComputed Tomography (HRCT) scan , including noninfectious pneumonitis

• Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) grade

2. caused by previous cancer therapy, excluding alopecia

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

• Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin,clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir,saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg.ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The requiredwashout period prior to starting study treatment is 2 weeks.

• Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin,rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort )or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The requiredwashout period prior to starting study treatment is 5 weeks for enzalutamide orphenobarbital and 3 weeks for other agents.

• Patients with prior hypersensitivity to monoclonal antibodies (mAb)

• Previous allogenic bone marrow transplant or double umbilical cord bloodtransplantation (dUCBT).

• Women who are pregnant or breastfeeding, and who do not agree to use a highlyeffective contraceptive method(s) while on study drug and for at least 3 monthsafter the last dose of MIRV and at least 6 months after the last dose of Olaparib.Females of childbearing potential must have a negative serum pregnancy test within 72 hours of study entry.

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

• Patients with duodenal stent or other GI disorder/defect that would interfere withabsorption of oral medication

• Includes patients unable to swallow orally administered medication and patientswith gastrointestinal disorders likely to interfere with absorption of thestudy medication

• Patients with known untreated or symptomatic central nervous system (CNS) metastases

• 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 theskin, or carcinoma in situ of the cervix or breast) are eligible

• Prior known hypersensitivity reaction to study drugs and/or any of their excipients

• Minor or major surgical procedure within 2 weeks of starting study treatment andpatients must have recovered from any effects of any major surgery.

• Inability to comply with study and follow-up procedures

• Patients deemed otherwise clinically unfit for clinical trial per investigatorsdiscretion