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

Prior treatment

• Patients who are planned to receive bevacizumab for the current relapse.
• Patients who underwent surgery for the current relapse with macroscopic complete resection
• Prior systemic anticancer therapy within 28 days before randomization
• Prior treatment with folate receptor-targeting investigational agents is not allowed.
• Serious concurrent illness or clinically-relevant active infection
• Previous clinical diagnosis of non-infectious interstitial lung disease, including non-infectious pneumonitis.
• Patients with prior hypersensitivity to monoclonal antibodies.

Other illness

• Ovarian tumors of low malignant potential (e.g. borderline tumors).
• Other malignancy within the last 3 years (except cervix or breast in situ carcinoma, type I stage I endometrial cancer)
• Known hypersensitivity to one of the chemotherapy re-gimes and/or PARP inhibitors and/or any of their excipients.

Age

• 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

Other

• Non-epithelial tumor origin of the ovary, the fallopian tube or the peritoneum (i.e. germ cell tumors)
• Unknown BRCA status.
• Patients with \> Grade 1 peripheral neuropathy.
• Required use of folate-containing supplements (e.g. folate deficiency)
• Women of childbearing potential (WOCBP) not protected by highly effective contraceptive methods.
• Pregnant and/or breast-feeding women.
• Patients with potential risks according to contraindication, warnings or interactions of the used chemotherapeutic agents as stated in the SmPCs are not eligible for participation in this trial.
• Patients with untreated or symptomatic central nervous system (CNS) metastases

• All patients must have a pathologically documented, definite diagnosis of epithelial cancer of the ovary, the fallopian tube or the peritoneum
• Relapsed disease with a platinum-free interval \>3 months
• All histologic subtypes of ovarian carcinoma including carcinosarcoma (malignant mixed Mullerian tumors, MMMT)
• 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.
• 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.
• Patients must have measurable disease or evaluable disease in combination with GCIG CA-125 criteria.
• Patients had one or more prior lines of chemotherapy. The last line of chemotherapy must have included platinum (min. 4 cycles) and has resulted in a partial or complete response.
• 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.
• Patients must have adequate hematological, liver, cardiac and kidney function:
  • Hemoglobin ≥ 10.0 g/dL.
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
  • Platelet count ≥ 100 x 109/L.
  • Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).
  • 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.
  • Serum creatinine ≤ 1.5 x institutional ULN and glomerular filtration rate of at least 40 ml/minute according to Cockroft-Gault formula.
• Patient is female and ≥18 years of age at the time of the first screening visit.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
• Patients must be willing and able to sign the informed consent form, and to adhere to the study visit schedule and other protocol requirements.
• 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, bilateral 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 8 months after end of treatment. Such methods include:
  • Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
  • oral
  • intravaginal
  • transdermal
  • Progestogen-only hormonal contraception associated with inhibition of ovulation:
  • oral
  • injectable
  • implantable
  • Intrauterine device (IUD)
  • Intrauterine hormone-releasing system (IUS)
  • Bilateral tubal occlusion
  • Vasectomized partner
  • Sexual abstinence