Mirvetuximab Soravtansine (MIRV) With Carboplatin in Second-line Treatment of Folate Receptor Alpha (FRα) Expressing, Platinum-sensitive Epithelial Ovarian Cancer

Phase 2

Active, not recruiting

• Conditions: High Grade Ovarian Cancer; Primary Peritoneal Cancer; Fallopian Tube Cancer
• Interventions: Drug: Mirvetuximab soravtansine; Drug: Carboplatin

• Registration Number: NCT05456685
• Lead Sponsor: AbbVie

Brief Summary

IMGN853-0420 is a multicenter, open-label, phase 2 study of carboplatin plus mirvetuximab soravtansine followed by mirvetuximab soravtansine continuation in folate receptor-alpha positive, recurrent platinum sensitive, high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancer following 1 prior line of platinum-based chemotherapy.

Detailed Description

This Phase 2 study is designed to evaluate the efficacy and safety of MIRV in combination with carboplatin followed by MIRV continuation in FRα-positive participants with recurrent platinum-sensitive ovarian cancer (PSOC) following 1 prior line of platinum-based chemotherapy. Upon completion of carboplatin plus MIRV combination chemotherapy (6 cycles), participants without progressive disease will continue on single-agent MIRV. Participants must have confirmation of FRα positivity by the Ventana folate receptor 1 (FOLR1) Assay.

Study Timeline

• Study First Submitted: 2022-06-29
• Study First Submitted QC: 2022-07-11
• Study First Posted: 2022-07-13
• Study Start: 2022-09-28
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-15
• Last Update Posted: 2024-11-19
• Primary Completion: 2025-06-30
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 125

Inclusion Criteria

1. Must be ≥ 18 years of age.

2. Must have an Eastern Cooperative Oncology Group Performance Status of 0 or 1.

3. Must have a confirmed diagnosis of high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer.

4. Must have relapsed after 1 prior line of platinum-based chemotherapy.

5. Must have platinum-sensitive disease defined as radiographic progression greater than 6 months from last dose of platinum-based chemotherapy.

   Note: Progression should be calculated from the date of the last administered dose of platinum therapy to the date of the radiographic imaging showing progression.

6. If available locally and is the standard of care, breast cancer susceptibility gene (BRCA) testing on the tumor or prior germline testing is required for eligibility, and will need to be done prior to study entry. Somatic and germline BRCA-positive participants must have received prior treatment with a poly adenosine phosphate-ribose polymerase inhibitor (PARPi) unless documented as clinically contraindicated.

7. Must have at least 1 lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the investigator).

8. Must provide an archival tumor tissue block or slides, or undergo procedure to obtain a new biopsy using a low-risk, medically routine procedure for immunohistochemistry (IHC) confirmation of FRα positivity; FRα-expressing tumors will be defined and classified by the Ventana FOLR1 Assay into low, medium, and high expressions defined as 25%-49%, 50%-74%, and ≥ 75% of tumor cells with PS2+ staining intensity, respectively. Must have confirmation of FRα positivity of ≥ 25% of tumor staining at ≥ 2+ intensity for entry into the study.

9. Must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia) and have discontinued any maintenance therapy at least 4 weeks before the first dose of carboplatin plus MIRV.

10. Must have completed any major surgery at least 4 weeks before the first dose of carboplatin plus MIRV and have recovered or stabilized from the side effects of prior surgery before the first dose of carboplatin plus MIRV.

11. Must have adequate hematologic, liver, and kidney functions defined as:

    1. Absolute neutrophil count ≥ 1.5 × 10^9/ liter(L) (1500/ microliter [μL]) without granulocyte colony-stimulating factor or long-acting white blood cell growth factors in the 10 days prior to the Cycle 1 Day 1 (C1D1) dose
    2. Platelet count ≥ 100 × 109/L (100,000/μL) without platelet transfusion in the 10 days prior to the C1D1 dose
    3. Hemoglobin ≥ 9.0 grams/deciliter (g/dL) without packed red blood cell transfusion in the 14 days prior to the C1D1 dose
    4. Serum creatinine ≤ 1.5 × upper limit of normal (ULN)
    5. Aspartate aminotransferase and alanine aminotransferase ≤ 3.0 × ULN
    6. Serum bilirubin ≤ 1.5 × ULN (participants with documented diagnosis of Gilbert syndrome are eligible if total bilirubin < 3.0 × ULN)
    7. Serum albumin ≥ 2 g/dL

12. Must be willing and able to sign the informed consent form (ICF) and to adhere to the protocol requirements.

13. Females of childbearing potential (FCBP) must agree to use highly effective contraceptive method(s) while on study medication and for at least 3 months after the last dose of MIRV and 6 months after the last dose of carboplatin.

14. FCBP must have a negative pregnancy test within the 4 days prior to the C1D1 dose.

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Exclusion Criteria

1. Participants with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above types, or low-grade/borderline ovarian tumor

2. More than one line of prior chemotherapy. Lines of prior anticancer therapy are counted with the following considerations:

   1. Neoadjuvant ± adjuvant therapies are considered 1 line of therapy if the neoadjuvant and adjuvant correspond to 1 fully predefined regimen; otherwise, they are counted as 2 prior regimens.
   2. Maintenance therapy (eg, bevacizumab, PARPi) will be considered part of the preceding line of therapy (ie, not counted independently).

3. Participants with prior wide-field radiotherapy affecting at least 20% of the bone marrow

4. Participants with > Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE)

5. Participants with active or chronic corneal disorders, history of corneal transplantation, or 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, or monocular vision

6. Participants with serious concurrent illness or clinically relevant active infection, including, but not limited to the following:

   1. Active hepatitis B virus (HBV) or hepatitis C virus (HCV)or C infection (whether or not on active antiviral therapy)
   2. HIV infection if inclusion clarifying eligibility for HIV positive participants is not met
   3. Active cytomegalovirus infection
   4. Any other concurrent infectious disease requiring IV antibiotics within 2 weeks prior to the first dose of carboplatin plus MIRV Note: Testing at screening is not required for the above infections unless clinically indicated.

7. Participants with a history of multiple sclerosis or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome)

8. Participants with clinically significant cardiac disease including, but not limited to, any of the following:

   1. Myocardial infarction ≤ 6 months prior to first dose
   2. Unstable angina pectoris
   3. Uncontrolled congestive heart failure (New York Heart Association > class II)
   4. Uncontrolled ≥ Grade 3 hypertension (per CTCAE)
   5. Uncontrolled cardiac arrhythmias

9. Participants with a history of hemorrhagic or ischemic stroke within 6 months prior to enrollment

10. Participants with a history of cirrhotic liver disease (Child-Pugh Class B or C)

11. Participants with a previous clinical diagnosis of noninfectious interstitial lung disease, including noninfectious pneumonitis (exception: Grade 1 noninfectious pneumonitis diagnosed on or within 6 weeks after treatment with an immunotherapeutic agent used in the treatment of their malignancy that has resolved per investigator or resolution of the radiologic findings)

12. Participants requiring use of folate-containing supplements (eg, folate deficiency)

13. Participants with prior hypersensitivity to monoclonal antibodies (mAb)

14. Females who are pregnant or breastfeeding

15. Participants who received prior treatment with MIRV or other FRα-targeting agents

16. Participants with untreated or symptomatic central nervous system metastases

17. Participants with a history of other malignancy within 3 years before enrollment Note: Participants with tumors with a negligible risk for metastasis or death (eg, adequately controlled basal-cell carcinoma or squamous-cell carcinoma of the skin, or carcinoma in situ of the cervix or breast) are eligible.

18. Prior known hypersensitivity reactions or known contraindications to study drugs or any of their excipients

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
MIRV + Carboplatin	Mirvetuximab soravtansine	On Day 1 of every 3-week cycle (Q3W) for 6 cycles, MIRV will be given at the dosage of 6 mg/kg of AIBW along with carboplatin given at area under the AUC5 administered through intravenous (IV) infusion (maximum dosing per National Comprehensive Cancer Network \[NCCN\] guidelines \[NCCN 2021\]). Upon completion of carboplatin plus MIRV treatment, single-agent MIRV will be continued at the tolerated dose on Day 1 Q3W in participants with investigator determined stable disease (SD), complete response (CR) or partial response (PR).
MIRV + Carboplatin	Carboplatin	On Day 1 of every 3-week cycle (Q3W) for 6 cycles, MIRV will be given at the dosage of 6 mg/kg of AIBW along with carboplatin given at area under the AUC5 administered through intravenous (IV) infusion (maximum dosing per National Comprehensive Cancer Network \[NCCN\] guidelines \[NCCN 2021\]). Upon completion of carboplatin plus MIRV treatment, single-agent MIRV will be continued at the tolerated dose on Day 1 Q3W in participants with investigator determined stable disease (SD), complete response (CR) or partial response (PR).

Primary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	Up to 3 years	ORR following carboplatin plus MIRV combination as measured by the investigator and assessed according to RECIST v1.1, defined as the proportion of confirmed responders (CR or PR) among participants with FRα expression of ≥ 50% of tumor cells with staining at ≥ 2+ intensity (PS2+) who have measurable disease per RECIST v1.1 at inclusion.; o ORR following carboplatin plus MIRV combination will also be measured, as a sensitivity analysis, by a blinded independent central review (BICR) in the same participant population

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	Up to 3 years	ORR, defined as the proportion of confirmed responders (CR or PR) following carboplatin plus MIRV combination, as measured by the investigator and assessed according to RECIST v1.1, among patients with FRα expression of ≥ 25% of tumor cells with PS2+ staining intensity who have measurable disease per RECIST v1.1 at inclusion.; o ORR will also be measured by a BICR, as a sensitivity analysis, in the same patient population.
Duration of Response (DOR)	Up to 3 years	DOR, defined as the time from first response to radiological progressive disease (PD) or death, whichever occurs first, following carboplatin plus MIRV followed by MIRV continuation by the investigator and assessed according to RECIST v1.1 among efficacy evaluable participants: * with FRα expression of ≥ 50% of tumor cells with PS2+ staining and; * with FRα expression of ≥ 25% of tumor cells with PS2+ staining; * DOR in the above populations will also be measured by BICR
Progression Free Survival (PFS)	Up to 3 years	PFS as measured by the investigator and by BICR in participants with; * FRα expression of ≥ 50% of tumor cells with PS2+ staining and; * FRα expression of ≥ 25% of tumor cells with PS2+ staining
Overall Survival (OS)	Up to 3 years	OS in participants with; * FRα expression of ≥ 50% of tumor cells with PS2+ staining and; * FRα of ≥ 25% of tumor cells with PS2+ staining
Cancer Antigen (CA)-125 Response	Up to 3 years	CA-125 response as measured by the investigator, per Gynecologic Cancer Intergroup (GCIG), in the efficacy evaluable participants with; * FRα expression of ≥ 50% of tumor cells with PS2+ staining and; * FRα expression of ≥ 25% of tumor cells with PS2+ staining
Number of Participants With treatment Emergent Adverse Events (TEAEs)	Up to 3 years

Trial Locations

Locations (70)

Northwestern Memorial Hospital; 🇺🇸 Chicago, Illinois, United States

UT Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Presbyterian Rust Medical Center/Jorgensen Cancer Center; 🇺🇸 Rio Rancho, New Mexico, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

California Pacific Medical Center; 🇺🇸 San Francisco, California, United States

University of California; 🇺🇸 Los Angeles, California, United States

Sarasota Memorial Health Care System; 🇺🇸 Sarasota, Florida, United States

University of California San Diego (UCSD) - Moores Cancer Center; 🇺🇸 La Jolla, California, United States

Northwestern University - Kishwaukee Cancer Center; 🇺🇸 DeKalb, Illinois, United States

START Madrid Fundación Jiménez Díaz; 🇪🇸 Madrid, Spain

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Israel Georgian Medical Research Clinic Healthycore; 🇬🇪 Tbilisi, Georgia

Hospital Teresa Herrera-Chuac; 🇪🇸 A Coruña, Spain

MD Anderson Cancer Center at Cooper; 🇺🇸 Camden, New Jersey, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Hospital Universitario De Badajoz; 🇪🇸 Badajoz, Spain

Hospital Universitario Reina Sofia; 🇪🇸 Córdoba, Spain

Hospital Dexeus; 🇪🇸 Barcelona, Spain

BC Cancer Vancouver; 🇨🇦 Vancouver, British Columbia, Canada

Center of Hope; 🇺🇸 Reno, Nevada, United States

H. U Arnau de Vilanova de Lleida; 🇪🇸 Lleida, Spain

CIUSSS de l'IIe-de-Montreal; 🇨🇦 Montréal, Quebec, Canada

Centre Hospitalier de l'Université de Montréal; 🇨🇦 Montréal, Quebec, Canada

Clinica Universidad de Navarra - Pamplona; 🇪🇸 Pamplona, Spain

Clinica Universidad de Navarra; 🇪🇸 Madrid, Spain

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

OU Health Stephenson Cancer Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Musgrove Park Hospital; 🇬🇧 Taunton, United Kingdom

Ciussse-Chus; 🇨🇦 Sherbrooke, Quebec, Canada

McGill University Health Centre; 🇨🇦 Montréal, Quebec, Canada

Hm Sanchinarro Ciocc; 🇪🇸 Madrid, Spain

Hospital Clinico de Valencia; 🇪🇸 Valencia, Spain

H Lee Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Hoag Hospital; 🇺🇸 Newport Beach, California, United States

Providence Medical Foundation; 🇺🇸 Fullerton, California, United States

University of Arizona Cancer Center; 🇺🇸 Tucson, Arizona, United States

Scripps MD Anderson Cancer Center; 🇺🇸 La Jolla, California, United States

University of Southern California; 🇺🇸 Los Angeles, California, United States

UC Davis Comprehensive Cancer Center; 🇺🇸 Sacramento, California, United States

Northwestern University - Warrenville Cancer Center; 🇺🇸 Warrenville, Illinois, United States

Northwestern University - Delnor Cancer Center; 🇺🇸 Geneva, Illinois, United States

Women's Cancer Care; 🇺🇸 Covington, Louisiana, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

New Mexico Cancer Care Alliance / University of New Mexico CCC; 🇺🇸 Albuquerque, New Mexico, United States

Holy Name Medical Center; 🇺🇸 Teaneck, New Jersey, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

Northwell Health; 🇺🇸 Whitestone, New York, United States

Duke Cancer Center; 🇺🇸 Durham, North Carolina, United States

Kadlec Clinic Hematology/Oncology; 🇺🇸 Kennewick, Washington, United States

Cliniques Universitaires Saint-Luc; 🇧🇪 Bruxelles, Belgium

UZLeuven; 🇧🇪 Leuven, Belgium

Vall d'Hebron Institute of Oncology; 🇪🇸 Barcelona, Spain

Catalan Institute of Oncology ICO; 🇪🇸 Barcelona, Spain

12 de Octubre University Hospital; 🇪🇸 Madrid, Spain

Hammersmith Hospital; 🇬🇧 London, United Kingdom

The Christie NUS Foundation Trust; 🇬🇧 Manchester, United Kingdom

Mount Vernon Cancer Centre; 🇬🇧 Northwood, United Kingdom

Nottingham University Hospitals NHS Trust; 🇬🇧 Nottingham, United Kingdom

CHU de Liege; 🇧🇪 Liège, Belgium

JSC Vian - Caraps Medline; 🇬🇪 Tbilisi, Georgia

Ltd - Consilium Medulla; 🇬🇪 Tbilisi, Georgia

LLC American Hospital Network; 🇬🇪 Tbilisi, Georgia

LTD "High Technology Hospital Medcenter"; 🇬🇪 Batumi, Georgia

Smilow Cancer Hospital; 🇺🇸 New Haven, Connecticut, United States

University of North Carolina at Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States

AdventHealth Orlando - Cancer Institute; 🇺🇸 Orlando, Florida, United States

Medical University of South Carolina - Hollings Cancer Center; 🇺🇸 Charleston, South Carolina, United States

Women & Infants Hospital of Rhode Island; 🇺🇸 Providence, Rhode Island, United States

The Royal Marsden NHS Foundation Trust; 🇬🇧 London, United Kingdom

Guy's Hospital; 🇬🇧 London, United Kingdom