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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT05456685
Other study ID # IMGN853-0420
Secondary ID 2022-002034-14
Status Active, not recruiting
Phase Phase 2
First received
Last updated
Start date September 28, 2022
Est. completion date December 31, 2026

Study information

Verified date April 2024
Source ImmunoGen, Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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 patients 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), patients without progressive disease will continue on single-agent MIRV. Patients must have confirmation of FRα positivity by the Ventana FOLR1 Assay.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 114
Est. completion date December 31, 2026
Est. primary completion date June 30, 2025
Accepts healthy volunteers No
Gender Female
Age group 18 Years and older
Eligibility Inclusion Criteria: 1. Patients must be = 18 years of age. 2. Patients must have an Eastern Cooperative Oncology Group Performance Status of 0 or 1. 3. Patients must have a confirmed diagnosis of high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer. 4. Patients must have relapsed after 1 prior line of platinum-based chemotherapy. 5. Patients 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. Prior BRCA testing on the tumor or prior germline testing is required for eligibility. If not done prior, tumor or germline testing will need to be done at study entry. Somatic and germline BRCA-positive patients must have received prior treatment with a PARPi. 7. Patients must have at least 1 lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the investigator). 8. Patients 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 FRa positivity; FRa-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. Patients must have confirmation of FRa positivity of = 25% of tumor staining at = 2+ intensity for entry into the study. 9. Patients 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. Patients 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. Patients must have adequate hematologic, liver, and kidney functions defined as: 1. Absolute neutrophil count = 1.5 × 109/L (1500/µL) without granulocyte colony-stimulating factor or long-acting white blood cell growth factors in the 10 days prior to the 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 g/dL without packed red blood cell transfusion in the 14 days prior to the C1D1 dose 4. Serum creatinine = 1.5 × ULN 5. Aspartate aminotransferase and alanine aminotransferase = 3.0 × ULN 6. Serum bilirubin = 1.5 × ULN (patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin < 3.0 × ULN) 7. Serum albumin = 2 g/dL 12. Patients 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. Patients 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. Patients with prior wide-field radiotherapy affecting at least 20% of the bone marrow 4. Patients with > Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE) 5. Patients 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. Patients with serious concurrent illness or clinically relevant active infection, including, but not limited to the following: 1. Active hepatitis B or C infection (whether or not on active antiviral therapy) 2. HIV infection 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. Patients with a history of multiple sclerosis or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome) 8. Patients 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. Patients with a history of hemorrhagic or ischemic stroke within 6 months prior to enrollment 10. Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C) 11. Patients 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. Patients requiring use of folate-containing supplements (eg, folate deficiency) 13. Patients with prior hypersensitivity to monoclonal antibodies (mAb) 14. Females who are pregnant or breastfeeding 15. Patients who received prior treatment with MIRV or other FRa-targeting agents 16. Patients with untreated or symptomatic central nervous system metastases 17. Patients with a history of other malignancy within 3 years before enrollment Note: patients 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 to study drugs or any of their excipients

Study Design


Intervention

Drug:
Mirvetuximab soravtansine
Mirvetuximab Soravtansine (MIRV) is an investigational antibody drug conjugate designed to selectively kill cancer cells. The antibody (protein) part of MIRV targets tumors by delivering a cell-killing drug to the tumor cells carrying a tumor-associated protein called folate receptor alpha (FRa). It is being developed for the treatment of subjects with recurrent platinum-sensitive, high grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with FRa expression. FRa positivity will be defined by the Ventana FOLR1 Assay.
Carboplatin
Carboplatin is considered to be the treatment agent of choice in relapsed PSOC.

Locations

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

Sponsors (1)

Lead Sponsor Collaborator
ImmunoGen, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Georgia,  Spain,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Other Correlate biomarker levels with response to treatment Correlate soluble FRa levels and other blood-based biomarkers with response to carboplatin plus MIRV treatment
Correlate tumor-based biomarkers and gene mutations with response to carboplatin plus MIRV combination
Up to 3 years
Other Correlate response in patients with prior PARPi use • Correlate response to carboplatin plus MIRV in patients following PARP inhibitor use Up to 3 years
Other Incidence of seroconversion Identify incidence of seroconversion of anti-drug antibodies (ADA) to MIRV when given in combination with carboplatin and
Identify association with carboplatin plus MIRV safety and efficacy
Up to 3 years
Primary Overall Response Rate (ORR) 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 (complete response [CR] or partial response [PR]) among patients with FRa expression of = 50% of tumor cells with PS2+ staining intensity 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 BICR (blinded independent central review) in the same patient population.
Up to 3 years
Secondary Overall Response Rate (ORR) 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 FRa 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.
Up to 3 years
Secondary Duration of Response (DOR) 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 patients:
with FRa expression of = 50% of tumor cells with PS2+ staining and
with FRa expression of = 25% of tumor cells with PS2+ staining
DOR in the above population will also be measured by BICR
Up to 3 years
Secondary Progression Free Survival (PFS) PFS as measured by the investigator and by BICR in patients with
FRa expression of = 50% of tumor cells with PS2+ staining and
FRa expression of = 25% of tumor cells with PS2+ staining
Up to 3 years
Secondary Overall Survival (OS) OS in patients with
FRa expression of = 50% of tumor cells with PS2+ staining and
FRa of = 25% of tumor cells with PS2+ staining
Up to 3 years
Secondary CA-125 Response CA-125 response as measured by the investigator, per GCIG, in the efficacy evaluable patients with
FRa expression of = 50% of tumor cells with PS2+ staining and
FRa expression of = 25% of tumor cells with PS2+ staining
Up to 3 years
Secondary Safety Parameters Treatment-emergent adverse events and laboratory test results, physical examination, or vital signs Up to 3 years
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