Overview

This is a multi-center, randomized, two-arm, open-label, comparative phase II trial of Mirvetuximab soravtansine (IMGN853), in folate receptor alpha (FRα) high recurrent ovarian cancer eligible for platinum-based chemotherapy.

Eligibility

Inclusion Criteria:

1. All patients must have a pathologically documented, definite diagnosis of epithelial cancer 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 (malignant mixed Mullerian tumors, MMMT)
4. Patients with wildtype BRCA1/2 mutation status or with a deleterious BRCA1/2 mutation in germline or somatic testing if they underwent PARP inhibitor therapy in previous treatment line.
5. Patients must be willing to provide archival tumor tissue from current relapse or previous 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) CDx assay.
          6. Patients must have measurable disease or evaluable disease in combination with GCIG
             CA-125 criteria.
          7. Patients had one or more prior lines of chemotherapy. The last line of chemotherapy
             should have included platinum and has resulted in a partial or complete response.
          8. Major surgery (not including placement of vascular access device, tumor punch/scrape
             biopsies or secondary wound closure) must be completed four weeks prior to Day 1.
          9. Patients must have adequate hematological, liver, cardiac and kidney function:
               1. Hemoglobin ≥ 10.0 g/dL.
               2. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
               3. Platelet count ≥ 100 x 109/L.
               4. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).
               5. 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 ≤ 5 x
                  ULN.
               6. Serum creatinine ≤ 1.5 x institutional ULN and glomerular filtration rate of at
                  least 40 ml/minute according to Cockroft-Gault formula.
         10. Patient is female and ≥18 years of age at the time of the first screening visit.
         11. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
         12. Patients must be willing and able to sign the informed consent form, and to adhere to
             the study visit schedule and other protocol requirements.
         13. Women of childbearing potential (a woman is considered of childbearing potential
             (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless
             permanently ster-ile. Permanent sterilization methods include hysterectomy, bi-lateral
             salpingectomy and bilateral oophorectomy) must have a negative serum pregnancy test
             within 3 days from day 1 of cycle 1 and agree to use a highly effective method of
             contraception while on study treatment and for at least 6 months after end of
             treatment. Such methods include:
               1. Combined (estrogen and progestogen containing) hor-monal contraception associated
                  with inhibition of ovulation:
                    -  oral
                    -  intravaginal
                    -  transdermal
               2. Progestogen-only hormonal contraception associated with inhibition of ovulation:
                    -  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 complete
             resection
          7. Prior systemic anticancer therapy within 28 days before randomization
          8. Prior treatment with folate receptor-targeting investigational agents is not allowed.
          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, including
             non-infectious pneumonitis.
         12. Active or chronic corneal disorders such as Sjogren's syndrome, Fuchs corneal
             dystrophy (requiring treatment), history of corneal transplantation, active herpetic
             keratitis, 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. Active or chronic corneal disorder
         13. Required use of folate-containing supplements (e.g. folate deficiency)
         14. Women of childbearing potential (WOCBP) not protected by highly effective
             contraceptive methods.
         15. Pregnant and/or breast-feeding women.
         16. Known hypersensitivity to one of the chemotherapy re-gimes and/or PARP inhibitors
             and/or any of their excipients.
         17. Patients with prior hypersensitivity to monoclonal antibodies.
         18. Patients with potential risks according to contraindication, warnings or interactions
             of the used chemotherapeutic agents as stated in the SmPCs are not eligible for
             partici-pation in this trial.
         19. Patients with untreated or symptomatic central nervous system (CNS) metastases