First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Mirvetuximab Soravtansine in Adults With Ovarian Cancer and Other Folate Receptor 1 (FOLR1)-Positive Solid Tumors

NCT ID: NCT01609556

Last Updated: 2021-02-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 206 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-28
• Study Completion Date: 2018-03-19

Brief Summary

The purpose of this study is to test mirvetuximab soravtansine (IMGN853) in participants with ovarian cancer and other FOLR-1 positive tumors.

Detailed Description

The study consists of a dose-escalation phase that will evaluate 2 dosing schedules (Schedule A and Schedule B) of mirvetuximab soravtansine and up to 5 dose-expansion groups at the maximum tolerated dose (MTD). The first 4 escalation cohorts will be single participant cohorts. Subsequent escalation cohorts will use a standard 3+3 design, with each cohort consisting of 3 or 4 to 6 participants. Data were collected and analysed for the escalation and expansion groups by dose schedule and not by individual dose.

Conditions

Tumors

Study Design

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

Study Groups

Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W)

Participants will receive mirvetuximab soravtansine intravenous (IV) infusion on Day 1 of every 21-day (every 3 weeks \[Q3W\]) cycle. Dose escalation for this group schedule will start at 0.15 milligrams per kilogram (mg/kg) and proceed through 7.0 mg/kg. Doses calculated initially based on participant's total body weight (TBW); then from protocol amendment 5 onwards, calculated based on adjusted ideal body weight (AIBW). Participants will continue to receive mirvetuximab soravtansine (for clinical benefit) until unacceptable toxicity or withdrawal of consent, whichever comes first, or until the sponsor terminate the study.

Group Type: EXPERIMENTAL

Mirvetuximab soravtansine

Intervention Type: DRUG

Mirvetuximab soravtansine IV infusion will be administered as per dose and schedule specified in the respective arms.

Dose Escalation: Schedule B (Mirvetuximab Soravtansine Weekly)

Participants will receive mirvetuximab soravtansine IV infusion on Days 1, 8, and 15 of every 28-day cycle. Dose escalation for this group schedule will start at 1.1 mg/kg (calculated based on AIBW) and proceed through 2.5 mg/kg. Participants will continue to receive mirvetuximab soravtansine (for clinical benefit) until unacceptable toxicity or withdrawal of consent, whichever comes first, or until the sponsor terminate the study.

Group Type: EXPERIMENTAL

Mirvetuximab soravtansine

Intervention Type: DRUG

Mirvetuximab soravtansine IV infusion will be administered as per dose and schedule specified in the respective arms.

Dose Expansion:EOC Participants(Mirvetuximab Soravtansine Q3W)

Participants with epithelial ovarian cancer (EOC) will receive mirvetuximab soravtansine 6.0 mg/kg (maximum tolerated dose \[MTD\]) IV infusion on Day 1 of every 21-day (Q3W) cycle (calculated based on AIBW). Participants will continue to receive mirvetuximab soravtansine (for clinical benefit) until unacceptable toxicity or withdrawal of consent, whichever comes first, or until the sponsor terminated the study.

Group Type: EXPERIMENTAL

Mirvetuximab soravtansine

Intervention Type: DRUG

Mirvetuximab soravtansine IV infusion will be administered as per dose and schedule specified in the respective arms.

Dose Expansion: EC Participants(Mirvetuximab Soravtansine Q3W)

Participants with endometrial cancer (EC) will receive mirvetuximab soravtansine 6.0 mg/kg (MTD) IV infusion on Day 1 of every 21-day (Q3W) cycle (calculated based on AIBW). Participants will continue to receive mirvetuximab soravtansine (for clinical benefit) until unacceptable toxicity or withdrawal of consent, whichever comes first, or until the sponsor terminate the study.

Group Type: EXPERIMENTAL

Mirvetuximab soravtansine

Intervention Type: DRUG

Mirvetuximab soravtansine IV infusion will be administered as per dose and schedule specified in the respective arms.

Interventions

Mirvetuximab soravtansine

Mirvetuximab soravtansine IV infusion will be administered as per dose and schedule specified in the respective arms.

Intervention Type: DRUG

Other Intervention Names

IMGN853

Eligibility Criteria

Inclusion Criteria

• Participants with advanced solid tumor that is refractory to standard treatment, for which no standard treatment is available, or the participant refuses standard therapy.
• Participants must be willing to provide an archival tumor tissue block or slides for biomarker analysis.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
• Time from prior therapy:

1. Systemic anti-neoplastic therapy: five half-lives or four weeks, whichever is shorter (6 weeks for prior nitrosoureas or mitomycin C).

2. Radiotherapy: wide-field radiotherapy (for example, greater than [>] 30 percent [%] of marrow-bearing bones) completed at least four weeks, or focal radiation completed at least two weeks, prior to starting study drug.

• Participants must have recovered or stabilized from all therapy-related toxicities.
• Major surgery (not including placement of vascular access device or tumor biopsies) must be completed four weeks prior to Day 1. Participants must have recovered or stabilized from the side effects prior to study treatment.
• Participants must have adequate hematologic, liver and kidney function.
• Participants with central nervous system (CNS) disease involvement are eligible if they have had brain metastases resected or have received radiation therapy ending at least 4 weeks prior to study day 1 and they meet all of the following criteria: Residual neurological symptoms less than or equal to (<=) Grade 1; No dexamethasone requirement; and Follow-up magnetic resonance imaging (MRI) shows no progression of treated lesions and no new lesions appearing.
• Participants must be willing and able to sign the informed consent form, and to adhere to the study visit schedule and other protocol requirements.
• Women of childbearing potential and men must agree to use effective contraceptive methods while on study and for at least twelve weeks after the last dose of study drug.
• Women of childbearing potential must have a negative pregnancy test prior to the first dose of study treatment.

Exclusion Criteria

• Grade >1 neuropathy.
• Any active or chronic corneal disorder, including, but not limited to the following: Sjogren's syndrome, Fuch's corneal dystrophy (requiring treatment), history of corneal transplantation, active herpetic keratitis, and also active ocular conditions requiring ongoing treatment/monitoring such as wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, presence of papilledema, acquired monocular vision.
• Serious concurrent illness, including, but not limited to the following:

1. Clinically relevant active infection including known active hepatitis B or C, Human Immunodeficiency Virus (HIV) infection, varicella-zoster virus (shingles) or cytomegalovirus infection or any other known concurrent infectious disease, requiring IV antibiotics within 2 weeks of study enrollment.

2. Significant cardiac disease such as recent myocardial infarction (<=6 months prior to Day 1), unstable angina pectoris, uncontrolled congestive heart failure (New York Heart Association >class II), uncontrolled hypertension (greater than or equal to [>=] Common Terminology Criteria for Adverse Events Version 4.03 [CTCAE v4.03] Grade 3), uncontrolled cardiac arrhythmias, severe aortic stenosis, or >=Grade 3 cardiac toxicity following prior chemotherapy.

3. History of multiple sclerosis or other demyelinating disease, Eaton-Lambert syndrome (para-neoplastic syndrome), history of hemorrhagic or ischemic stroke within the last six months, or alcoholic liver disease.

4. Previous clinical diagnosis of treatment-related pneumonitis.

• Any other concomitant anti-cancer treatment such as immunotherapy, biotherapy, radiotherapy, chemotherapy, investigative therapy, or high-dose steroids; however, low dose steroids and Luteinizing Hormone Releasing Hormone (LHRH) at doses that have been stable for >=14 days are permitted for participants with prostate cancer.
• Known hypersensitivity to previous monoclonal antibody therapy or maytansinoids.
• Prior history of solid tumor malignancy within the last 3 years except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ prostate cancer (participants must have shown no evidence of active disease for 2 years prior to enrollment).
• Concomitant administration of folate-containing vitamins.
• Participants who have received prior allogeneic or autologous bone marrow transplants.
• Women of childbearing potential who are pregnant or breast feeding.

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

Sponsors

ImmunoGen, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Kansas Medical Center Research Institute

Fairway, Kansas, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Ohio State University

Columbus, Ohio, United States

University of Oklahoma Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

CTRC at the University of Texas Health Science Center

San Antonio, Texas, United States

Princess Margaret Hospital

Toronto, Ontario, Canada

McGill University Health Centre

Montreal, Quebec, Canada

Countries

United States; Canada

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

IMGN853-0401

Identifier Type: -

Identifier Source: org_study_id