Status:
ACTIVE_NOT_RECRUITING
Mirvetuximab Soravtansine (IMGN853), in Folate Receptor Alpha (FRα) High Recurrent Ovarian Cancer
Lead Sponsor:
AGO Research GmbH
Conditions:
Recurrent Epithelial Ovarian, Fallopian or Peritoneal Carcinoma
Eligibility:
FEMALE
18+ years
Phase:
PHASE2
Brief Summary
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 pl...
Detailed Description
136 patients will be randomized into the follow-ing two treatment arms as specified below: Arm A: Control arm Platinum-based chemotherapy Arm B: Carboplatin + Mirvetuximab soravtansine (IMGN853)
Eligibility Criteria
Inclusion
- 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 should have included platinum 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, 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:
- Combined (estrogen and progestogen containing) hor-monal 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
Exclusion
- Non-epithelial tumor origin of the ovary, the fallopian tube or the peritoneum (i.e. germ cell tumors)
- Ovarian tumors of low malignant potential (e.g. borderline tumors).
- Unknown BRCA status.
- Patients who are planned to receive bevacizumab for the current relapse.
- Other malignancy within the last 3 years (except cervix or breast in situ carcinoma, type I stage I endometrial cancer)
- 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.
- Patients with \> Grade 1 peripheral neuropathy.
- Serious concurrent illness or clinically-relevant active infection
- Previous clinical diagnosis of non-infectious interstitial lung disease, including non-infectious pneumonitis.
- 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
- 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.
- Known hypersensitivity to one of the chemotherapy re-gimes and/or PARP inhibitors and/or any of their excipients.
- Patients with prior hypersensitivity to monoclonal antibodies.
- 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.
- Patients with untreated or symptomatic central nervous system (CNS) metastases
Key Trial Info
Start Date :
October 13 2021
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 1 2026
Estimated Enrollment :
136 Patients enrolled
Trial Details
Trial ID
NCT04274426
Start Date
October 13 2021
End Date
December 1 2026
Last Update
April 6 2025
Active Locations (19)
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1
Charite Campus Virchow Klinikum
Berlin, Germany
2
Städtische Klinikum Dessau
Dessau, Germany
3
Universitätsklinikum Carl-Gustav-Carus an der Technischen Universität Dresden
Dresden, Germany
4
Evangelische Kliniken-Essen-Mitte
Essen, Germany