IMGN853 With Carboplatin in Second-line Treatment of FRα Expressing, Platinum-sensitive Epithelial Ovarian Cancer

Fallopian Tube Cancer Clinical Trial

Official title:

Multicenter, Open-label, ph 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05456685
• Other study ID #: IMGN853-0420
• Secondary ID: 2022-002034-14
• Status: Recruiting
• Phase: Phase 2
• Start date: September 28, 2022
• Est. completion date: December 31, 2026

Study information

• Verified date: March 2024
• Source: ImmunoGen, Inc.
• Contact: ImmunoGen, Inc.
• Phone: 781-895-0600
• Email: medicalaffairs[@]immunogen.com
• Is FDA regulated: No
• 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: Recruiting
• Enrollment: 114
• Est. completion date: December 31, 2026
• Est. primary completion date: June 30, 2024
• 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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Hypersensitivity
• Ovarian Neoplasms
• Primary Peritoneal Cancer

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	Women's Cancer Research Network	Fresno	California
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