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

NCT ID: NCT04274426

Last Updated: 2025-04-06

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 136 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-13
• Study Completion Date: 2026-12-31

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)

Conditions

Recurrent Epithelial Ovarian, Fallopian or Peritoneal Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Control arm with Platinum-based chemotherapy

1. Carboplatin (AUC5, d1) combined with pegylated liposomal doxorubicin (PLD) (30 mg/m², d1) q28d

2. Carboplatin (AUC4, d1) combined with gemcitabine (1000 mg/m2, d1 & d8) q21d

3. Carboplatin (AUC5, d1) combined with paclitaxel (175 mg/m², d1) q21d

Group Type: ACTIVE_COMPARATOR

Carboplatin

Intervention Type: DRUG

Carboplatin will administered by intravenous route

Pegylated liposomal doxorubicin (PLD)

Intervention Type: DRUG

PLD will be administered by intravenous route

Gemcitabine

Intervention Type: DRUG

Gemcitabine will be administered by intravenous route

Paclitaxel

Intervention Type: DRUG

Paclitaxel will be administered by intravenous route

Carboplatin + Mirvetuximab soravtansine (IMGN853)

Carboplatin (AUC5, d1) + Mirvetuximab soravtansine (IMGN853) 6 mg/kg IV d1 x 6 cycles q21d, followed by subsequent monotherapy of Mirvetuximab soravtansine (IMGN853) 6 mg/kg IV q3w until disease progression.

Group Type: EXPERIMENTAL

Carboplatin

Intervention Type: DRUG

Carboplatin will administered by intravenous route

Mirvetuximab Soravtansine

Intervention Type: DRUG

Mirvetuximab Soravtansine will be administered by intravenous route

Interventions

Carboplatin

Carboplatin will administered by intravenous route

Intervention Type: DRUG

Pegylated liposomal doxorubicin (PLD)

PLD will be administered by intravenous route

Intervention Type: DRUG

Gemcitabine

Gemcitabine will be administered by intravenous route

Intervention Type: DRUG

Paclitaxel

Paclitaxel will be administered by intravenous route

Intervention Type: DRUG

Mirvetuximab Soravtansine

Mirvetuximab Soravtansine will be administered by intravenous route

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

AGO Research GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philipp Harter

Role: STUDY_CHAIR

Kliniken Essen-Mitte, Germany

Locations

Charite Campus Virchow Klinikum

Berlin, , Germany

Städtische Klinikum Dessau

Dessau, , Germany

Universitätsklinikum Carl-Gustav-Carus an der Technischen Universität Dresden

Dresden, , Germany

Evangelische Kliniken-Essen-Mitte

Essen, , Germany

Universitätsklinikum Frankfurt

Frankfurt, , Germany

Mammazentrum HH am Krankenhaus Jerusalem

Hamburg, , Germany

Universitätsklinikum Hamburg Eppendorf

Hamburg, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

ViDia Christliche Kliniken Karlsruhe

Karlsruhe, , Germany

St. Elisabeth-Krankenhaus GmbH

Köln-Hohenlind, , Germany

HELIOS Klinikum Krefeld

Krefeld, , Germany

Klinikum Mannheim

Mannheim, , Germany

OnkoNet Marburg

Marburg, , Germany

Klinikum der Universität München

München, , Germany

Rotkreuzklinikum München

München, , Germany

TU München, Klinikum recht der Isar

München, , Germany

Universitätsklinik Münster

Münster, , Germany

Klinikum Südstadt Rostock

Rostock, , Germany

Universitätsfrauenklinik Ulm

Ulm, , Germany

Countries

Germany

Related Links

http://www.ago-ovar.de/

Related Info

Other Identifiers

2018-004207-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AGO-OVAR 2.34

Identifier Type: -

Identifier Source: org_study_id