Clinical trial NCT05456685: Mirvetuximab Soravtansine (MIRV) With Carboplatin in Second-line Treatment of Folate Receptor Alpha (FRα) Expressing, Platinum-sensitive Epithelial Ovarian Cancer
Official title: Multicenter, Open-label, Phase 2 Study of Carboplatin Plus Mirvetuximab Soravtansine Followed by Mirvetuximab Soravtansine Continuation in FRα Positive, Recurrent Platinum-sensitive, High-grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers Following 1 Prior Line of Platinum-based Chemotherapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: High Grade Ovarian Cancer
Primary Peritoneal Cancer
Fallopian Tube Cancer
Keywords: platinum sensitive, folate-receptor alpha expression, antibody-drug conjugate, cancer, ovarian neoplasm, high-grade ovarian
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2022-07-13
Enrollment: 125
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Open-label study with treatment cycles every three weeks. All participants will receive 6 cycles of carboplatin (area under the concentration curve \[AUC\] 5) + MIRV (6 milligrams per kilogram \[mg/kg\] of adjusted ideal body weight \[AIBW\]). If participants have no progressive disease (PD) at the end of the combination treatment, they will continue to maintenance MIRV (6 mg/kg of AIBW) as a single agent.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

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

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 3 years
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 3 years
measure: Duration of Response (DOR)
timeFrame: Up to 3 years
measure: Progression Free Survival (PFS)
timeFrame: Up to 3 years
measure: Overall Survival (OS)
timeFrame: Up to 3 years
measure: Cancer Antigen (CA)-125 Response
timeFrame: Up to 3 years
measure: Number of Participants With treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: Fullerton
country: United States
facility: Providence Medical Foundation
state: California
city: La Jolla
country: United States
facility: Scripps MD Anderson Cancer Center
state: California
city: La Jolla
country: United States
facility: University of California San Diego (UCSD) - Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: University of California
state: California
city: Newport Beach
country: United States
facility: Hoag Hospital
state: California
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: New Haven
country: United States
facility: Smilow Cancer Hospital
state: Connecticut
city: Orlando
country: United States
facility: AdventHealth Orlando - Cancer Institute
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Health Care System
state: Florida
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: DeKalb
country: United States
facility: Northwestern University - Kishwaukee Cancer Center
state: Illinois
city: Geneva
country: United States
facility: Northwestern University - Delnor Cancer Center
state: Illinois
city: Warrenville
country: United States
facility: Northwestern University - Warrenville Cancer Center
state: Illinois
city: Covington
country: United States
facility: Women's Cancer Care
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Reno
country: United States
facility: Center of Hope
state: Nevada
city: Camden
country: United States
facility: MD Anderson Cancer Center at Cooper
state: New Jersey
city: Teaneck
country: United States
facility: Holy Name Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Cancer Care Alliance / University of New Mexico CCC
state: New Mexico
city: Rio Rancho
country: United States
facility: Presbyterian Rust Medical Center/Jorgensen Cancer Center
state: New Mexico
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Whitestone
country: United States
facility: Northwell Health
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
city: Oklahoma City
country: United States
facility: OU Health Stephenson Cancer Center
state: Oklahoma
city: Providence
country: United States
facility: Women & Infants Hospital of Rhode Island
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina - Hollings Cancer Center
state: South Carolina
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Kennewick
country: United States
facility: Kadlec Clinic Hematology/Oncology
state: Washington
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Leuven
country: Belgium
facility: UZLeuven
city: Liège
country: Belgium
facility: CHU de Liege
city: Vancouver
country: Canada
facility: BC Cancer Vancouver
state: British Columbia
city: Montréal
country: Canada
facility: CIUSSS de l'IIe-de-Montreal
state: Quebec
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal
state: Quebec
city: Montréal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Sherbrooke
country: Canada
facility: Ciussse-Chus
state: Quebec
city: Batumi
country: Georgia
facility: LTD "High Technology Hospital Medcenter"
city: Tbilisi
country: Georgia
facility: LLC American Hospital Network
city: Tbilisi
country: Georgia
facility: Israel Georgian Medical Research Clinic Healthycore
city: Tbilisi
country: Georgia
facility: JSC Vian - Caraps Medline
city: Tbilisi
country: Georgia
facility: Ltd - Consilium Medulla
city: A Coruña
country: Spain
facility: Hospital Teresa Herrera-Chuac
city: Badajoz
country: Spain
facility: Hospital Universitario De Badajoz
city: Barcelona
country: Spain
facility: Hospital Dexeus
city: Barcelona
country: Spain
facility: Vall d'Hebron Institute of Oncology
city: Barcelona
country: Spain
facility: Catalan Institute of Oncology ICO
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Lleida
country: Spain
facility: H. U Arnau de Vilanova de Lleida
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra
city: Madrid
country: Spain
facility: START Madrid Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: 12 de Octubre University Hospital
city: Madrid
country: Spain
facility: Hm Sanchinarro Ciocc
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra - Pamplona
city: Valencia
country: Spain
facility: Hospital Clinico de Valencia
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
state: Surrey
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: Manchester
country: United Kingdom
facility: The Christie NUS Foundation Trust
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Taunton
country: United Kingdom
facility: Musgrove Park Hospital
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: