Mirvetuximab Soravtansine (IMGN853), in Folate Receptor Alpha (FRα) High Recurrent Ovarian Cancer

Inclusion Criteria:

1. All patients must have a pathologically documented, definite diagnosis of epithelialcancer of the ovary, the fallopian tube or the peritoneum

2. Relapsed disease with a platinum-free interval >3 months

3. All histologic subtypes of ovarian carcinoma including carcinosarcoma (malignantmixed Mullerian tumors, MMMT)

4. Patients with wildtype BRCA1/2 mutation status or with a deleterious BRCA1/2mutation in germline or somatic testing if they underwent PARP inhibitor therapy inprevious treatment line.

5. Patients must be willing to provide archival tumor tissue from current relapse orprevious surgeries/biopsies for central confirmation of FRα high status by PS2+scoring: all tumors must exhibit ≥75% of tumor cells with FRα membrane staining and ≥ 2+intensity by immunohistochemistry (IHC) using the Ventana FOLR1 (FOLR1 2.1) CDxassay.

6. Patients must have measurable disease or evaluable disease in combination with GCIGCA-125 criteria.

7. Patients had one or more prior lines of chemotherapy. The last line of chemotherapyshould have included platinum and has resulted in a partial or complete response.

8. Major surgery (not including placement of vascular access device, tumor punch/scrapebiopsies or secondary wound closure) must be completed four weeks prior to Day 1.

9. Patients must have adequate hematological, liver, cardiac and kidney function:

10. Hemoglobin ≥ 10.0 g/dL.

11. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

12. Platelet count ≥ 100 x 109/L.

13. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).

14. Aspartate aminotransferase/Serum Glutamic Oxaloacetic Transaminase (ASAT/SGOT))and Alanine aminotransferase/Serum Glutamic Pyruvate Transaminase (ALAT/SGPT)) ≤ 2.5 x ULN, unless liver metastases are present in which case they must be ≤ 5x ULN.

15. Serum creatinine ≤ 1.5 x institutional ULN and glomerular filtration rate of atleast 40 ml/minute according to Cockroft-Gault formula.

16. Patient is female and ≥18 years of age at the time of the first screening visit.

17. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.

18. Patients must be willing and able to sign the informed consent form, and to adhereto the study visit schedule and other protocol requirements.

19. Women of childbearing potential (a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unlesspermanently ster-ile. Permanent sterilization methods include hysterectomy,bi-lateral salpingectomy and bilateral oophorectomy) must have a negative serumpregnancy test within 3 days from day 1 of cycle 1 and agree to use a highlyeffective method of contraception while on study treatment and for at least 6 monthsafter end of treatment. Such methods include:

20. Combined (estrogen and progestogen containing) hor-monal contraceptionassociated with inhibition of ovulation:

• oral
• intravaginal
• transdermal

2. Progestogen-only hormonal contraception associated with inhibition ofovulation:

• oral
• injectable
• implantable

3. Intrauterine device (IUD)

4. Intrauterine hormone-releasing system ( IUS)

5. Bilateral tubal occlusion

6. Vasectomized partner

7. Sexual abstinence

Exclusion Criteria:

1. Non-epithelial tumor origin of the ovary, the fallopian tube or the peritoneum (i.e.germ cell tumors)

2. Ovarian tumors of low malignant potential (e.g. borderline tumors).

3. Unknown BRCA status.

4. Patients who are planned to receive bevacizumab for the current relapse.

5. Other malignancy within the last 3 years (except cervix or breast in situ carcinoma,type I stage I endometrial cancer)

6. Patients who underwent surgery for the current relapse with macroscopic completeresection

7. Prior systemic anticancer therapy within 28 days before randomization

8. Prior treatment with folate receptor-targeting investigational agents is notallowed.

9. Patients with > Grade 1 peripheral neuropathy.

10. Serious concurrent illness or clinically-relevant active infection

11. Previous clinical diagnosis of non-infectious interstitial lung disease, includingnon-infectious pneumonitis.

12. Active or chronic corneal disorders such as Sjogren's syndrome, Fuchs cornealdystrophy (requiring treatment), history of corneal transplantation, active herpetickeratitis, active ocular conditions requiring ongoing treatment/monitoring such asuncontrolled glaucoma, wet age-related macular degeneration requiring intravitrealinjections, active diabetic retinopathy with macular edema, macular degeneration,presence of papilledema, and /or monocular vision. Active or chronic cornealdisorder

13. Required use of folate-containing supplements (e.g. folate deficiency)

14. Women of childbearing potential (WOCBP) not protected by highly effectivecontraceptive methods.

15. Pregnant and/or breast-feeding women.

16. Known hypersensitivity to one of the chemotherapy re-gimes and/or PARP inhibitorsand/or any of their excipients.

17. Patients with prior hypersensitivity to monoclonal antibodies.

18. Patients with potential risks according to contraindication, warnings orinteractions of the used chemotherapeutic agents as stated in the SmPCs are noteligible for partici-pation in this trial.

19. Patients with untreated or symptomatic central nervous system (CNS) metastases