Clinical trial NCT04274426: Mirvetuximab Soravtansine (IMGN853), in Folate Receptor Alpha (FRα) High Recurrent Ovarian Cancer
Official title: A Randomized Phase II Trial of Mirvetuximab Soravtansine (IMGN853), in Folate Receptor Alpha (FRα) High Recurrent Ovarian Cancer Eligible for Platinum-based Chemotherapy. Supported by: DIAGNOSTIC PROTOCOL for the VENTANA FOLR1 (FOLR1-2.1) CDx Assay Ventana No. RD004881; Protocol Document No. D152967
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Recurrent Epithelial Ovarian, Fallopian or Peritoneal Carcinoma
Lead sponsor: AGO Research GmbH
Sponsor class: INDUSTRY
First posted: 2020-02-18
Enrollment: 136
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 platinum-based chemotherapy.

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 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

Primary outcomes:
measure: Progression free survival (PFS) defined as the time from randomization to progressive disease (PD) or death, whichever occurs earlier. PD is based on investigator assess-ment using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
timeFrame: Up to 2.5 years. From date of randomization until date of progressive disease (PD) or death, whichever occurs earlier.
Secondary outcomes:
measure: OS
timeFrame: Up to 2.5 years. From date of randomization until date of death from any cause.
measure: ORR
timeFrame: Up to 2.5 years. From date of randomization to date of death death from any cause.
measure: Efficacy regarding PFS
timeFrame: Up to 2.5 years. From date of randomization to date of death from any cause.
measure: Efficacy regarding OS
timeFrame: Up to 2.5 years. From date of randomization to date of death from any cause.
measure: Efficacy regarding ORR
timeFrame: Up to 2.5 years. From date of randomization to date of death from any cause.
measure: Serological progressive disease
timeFrame: Up to 2.5 years. From date of randomization to date of death death from any cause.
measure: Time to first subsequent treatment (TFST)
timeFrame: Up to 2.5 years. From date of randomization to date of death from any cause.
measure: Time to second subsequent treatment (TSST)
timeFrame: Up to 2.5 years. From date of randomization until date of death from any cause.
measure: Patient-reported outcomes
timeFrame: Up to 2.5 years. From date of randomization until date of death from any cause.
measure: Patient-reported outcomes
timeFrame: Up to 2.5 years. From date of randomization until date of death from any cause.
measure: Safety and tolerability
timeFrame: Up to 2.5 years. From date of randomization until date of death from any cause through study completion.
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charite Campus Virchow Klinikum
city: Dessau
country: Germany
facility: Städtische Klinikum Dessau
city: Dresden
country: Germany
facility: Universitätsklinikum Carl-Gustav-Carus an der Technischen Universität Dresden
city: Essen
country: Germany
facility: Evangelische Kliniken-Essen-Mitte
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
city: Hamburg
country: Germany
facility: Mammazentrum HH am Krankenhaus Jerusalem
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg Eppendorf
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Karlsruhe
country: Germany
facility: ViDia Christliche Kliniken Karlsruhe
city: Krefeld
country: Germany
facility: HELIOS Klinikum Krefeld
city: Köln-Hohenlind
country: Germany
facility: St. Elisabeth-Krankenhaus GmbH
city: Mannheim
country: Germany
facility: Klinikum Mannheim
city: Marburg
country: Germany
facility: OnkoNet Marburg
city: München
country: Germany
facility: Klinikum der Universität München
city: München
country: Germany
facility: Rotkreuzklinikum München
city: München
country: Germany
facility: TU München, Klinikum recht der Isar
city: Münster
country: Germany
facility: Universitätsklinik Münster
city: Rostock
country: Germany
facility: Klinikum Südstadt Rostock
city: Ulm
country: Germany
facility: Universitätsfrauenklinik Ulm
Study officials:
affiliation: Kliniken Essen-Mitte, Germany
name: Philipp Harter
role: STUDY_CHAIR
References: