RECRUITING

First in Human Study of IMGN151 in Recurrent Gynaecological Cancers

Conditions

Endometrial Cancer High Grade Serous Adenocarcinoma of Ovary Primary Peritoneal Carcinoma Fallopian Tube Cancer Cervical Cancer Antibody Drug Conjugate Platinum-Resistant Recurrent

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

IIMGN151-1001 is a Phase 1, first in human, open-label dose-escalation, optimization, and expansion study designed to characterize the safety, tolerability, pharmacokinetics (PK), immunogenicity, and preliminary antitumor activity of IMGN151 in adult participants with recurrent endometrial cancer; recurrent, high-grade serous epithelial ovarian, fallopian tube, and primary peritoneal cancers; or recurrent cervical cancers. All participants will be, in the opinion of the investigator, appropriate for nonplatinum single-agent therapy for their next line of therapy.

Official Title

A Phase 1, First-in-Human, Open-Label, Dose-Escalation and Expansion Study of IMGN151 (Anti-FRα Antibody-drug Conjugate) in Adult Patients With Recurrent Gynaecological Cancers

Quick Facts

Study Start:2023-01-11

Study Completion:2025-12-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05527184

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:FEMALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1. 2. Dose-Escalation Phase: Recurrent endometrial cancer or high-grade serous epithelial ovarian, fallopian tube, and primary peritoneal cancer (EOC) and who have exhausted appropriate standard-of-care therapy. 3. Dose Optimization: 4. Expansion Phase: 1. For Cohort A, recurrent endometrial cancer (high-grade endometrioid or serous histology only) with 1-3 prior lines of therapy. 2. For Cohort B, PROC with no previous FRα-directed therapy and no more than 5 prior lines of therapy, with no more than 2 prior therapies since development of platinum resistance. 3. For Cohort C, PROC with previous FRα-directed therapy with at least one intervening anticancer therapy between prior FRα-directed therapy and IMGN151. 4. For Cohort D, non-high-grade serous EOC including the following histologies: carcinosarcoma, endometrioid, and low-grade serous carcinoma and have exhausted appropriate standard-of-care therapy. 5. For Cohort E, cervical cancer including the following histologies: squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma with 1-4 prior lines of therapy. 6. For participants with endometrial or cervical cancer with Combined Positive Score (CPS) \> 1, prior checkpoint inhibitor therapy, alone or in combination, is required if available locally and medically appropriate. 5. Evaluable lesions 1. Dose-Escalation Phase: Participants may have radiologically evaluable or nonevaluable disease. 2. Dose Optimization and Expansion Phase: Participants must have at least 1 lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the investigator). 6. Willing to provide an archival tumor tissue block or slides or to undergo a procedure to obtain a new biopsy using a low-risk, medically routine procedure. 7. Participants must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia or hemoglobin within 10 days before Cycle 1 Day 1). 8. Participants must have completed any major surgery at least 4 weeks prior to first dose of IMGN151 and have recovered or stabilized from the side effects of prior surgery prior to first dose of IMGN151. 9. Participants must have adequate organ and bone marrow function.	1. Participants with ovarian cancer with histologies including clear cell, mucinous, or borderline ovarian tumor. 1. With the exception of participants enrolled in Cohort D, participants with ovarian cancer with histologies including endometrioid, sarcomatous histology, mixed tumors containing any of the above histologies, as well as low-grade serous carcinoma. 2. For Cohort A, participants with endometrial cancer with histologies other than high-grade serous or high-grade endometrioid. 3. For Cohort E, participants with cervical cancer with histologies other than adenocarcinoma, squamous cell carcinoma, and adenosquamous carcinoma. 2. For Cohort B and Dose Optimization: participants with primary platinum refractory ovarian cancer from disease progression or within 3 months of first platinum-based treatment. 3. Radiation therapy of \> 20% of the potential bone marrow 4. Participants with \> Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 5. Participants with the following ocular history and/or concurrent disorders: 1. Active or chronic corneal epithelial disorders other than non-confluent superficial keratopathy/keratitis, including confluent superficial punctate keratopathy/keratitis (SPK) not expected to resolve to non-confluence or better within the screening window with standard-of-care intervention 2. History of corneal transplantation 3. Undergoing active postoperative management for refractive surgery, cataract surgery, corneal cross-linking, or corneal complications of surgery 4. Active or chronic clinically significant (≥ Grade 3) corneal disorders (for example, Fuch's dystrophy or neurotrophic keratitis) 5. Active ocular conditions requiring ongoing treatment/monitoring, such as glaucoma, which is not adequately controlled with medication or surgery, wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, presence of papilledema, an ocular condition with high risk of retinal detachment 6. Monocular vision with visual acuity in the worse-seeing eye (worse than 20/200 or visual fields less than 20 degrees) 6. Serious concurrent illness or clinically relevant active infection. 7. A history of multiple sclerosis or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome) 8. Participants with clinically significant cardiac disease. 9. A history of hemorrhagic or ischemic stroke within 6 months before enrollment 10. A history of cirrhotic liver disease (Child-Pugh Class B or C) 11. Participants with evidence of pneumonitis on baseline imaging or Participants with a previous clinical diagnosis of noninfectious interstitial lung disease (ILD), including noninfectious pneumonitis 12. Participants with prior hypersensitivity to monoclonal antibodies (mAb) 13. Females who are pregnant or breastfeeding 14. For Dose Optimization and Expansion Phase: Participants who received a prior FRα-targeting agent, with the exception of participants enrolled in the prior FRα-targeting agent, ovarian cancer cohort (Cohort C). 15. Untreated or symptomatic central nervous system metastases 16. A history of other malignancy within 3 years before enrollment

Inclusion Criteria

Exclusion Criteria

1. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
2. Dose-Escalation Phase: Recurrent endometrial cancer or high-grade serous epithelial ovarian, fallopian tube, and primary peritoneal cancer (EOC) and who have exhausted appropriate standard-of-care therapy.
3. Dose Optimization:
4. Expansion Phase:
1. For Cohort A, recurrent endometrial cancer (high-grade endometrioid or serous histology only) with 1-3 prior lines of therapy.
2. For Cohort B, PROC with no previous FRα-directed therapy and no more than 5 prior lines of therapy, with no more than 2 prior therapies since development of platinum resistance.
3. For Cohort C, PROC with previous FRα-directed therapy with at least one intervening anticancer therapy between prior FRα-directed therapy and IMGN151.
4. For Cohort D, non-high-grade serous EOC including the following histologies: carcinosarcoma, endometrioid, and low-grade serous carcinoma and have exhausted appropriate standard-of-care therapy.
5. For Cohort E, cervical cancer including the following histologies: squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma with 1-4 prior lines of therapy.
6. For participants with endometrial or cervical cancer with Combined Positive Score (CPS) \> 1, prior checkpoint inhibitor therapy, alone or in combination, is required if available locally and medically appropriate.
5. Evaluable lesions
1. Dose-Escalation Phase: Participants may have radiologically evaluable or nonevaluable disease.
2. Dose Optimization and Expansion Phase: Participants must have at least 1 lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the investigator).
6. Willing to provide an archival tumor tissue block or slides or to undergo a procedure to obtain a new biopsy using a low-risk, medically routine procedure.
7. Participants must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia or hemoglobin within 10 days before Cycle 1 Day 1).
8. Participants must have completed any major surgery at least 4 weeks prior to first dose of IMGN151 and have recovered or stabilized from the side effects of prior surgery prior to first dose of IMGN151.
9. Participants must have adequate organ and bone marrow function.

1. Participants with ovarian cancer with histologies including clear cell, mucinous, or borderline ovarian tumor.
1. With the exception of participants enrolled in Cohort D, participants with ovarian cancer with histologies including endometrioid, sarcomatous histology, mixed tumors containing any of the above histologies, as well as low-grade serous carcinoma.
2. For Cohort A, participants with endometrial cancer with histologies other than high-grade serous or high-grade endometrioid.
3. For Cohort E, participants with cervical cancer with histologies other than adenocarcinoma, squamous cell carcinoma, and adenosquamous carcinoma.
2. For Cohort B and Dose Optimization: participants with primary platinum refractory ovarian cancer from disease progression or within 3 months of first platinum-based treatment.
3. Radiation therapy of \> 20% of the potential bone marrow
4. Participants with \> Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE) v5.0
5. Participants with the following ocular history and/or concurrent disorders:
1. Active or chronic corneal epithelial disorders other than non-confluent superficial keratopathy/keratitis, including confluent superficial punctate keratopathy/keratitis (SPK) not expected to resolve to non-confluence or better within the screening window with standard-of-care intervention
2. History of corneal transplantation
3. Undergoing active postoperative management for refractive surgery, cataract surgery, corneal cross-linking, or corneal complications of surgery
4. Active or chronic clinically significant (≥ Grade 3) corneal disorders (for example, Fuch's dystrophy or neurotrophic keratitis)
5. Active ocular conditions requiring ongoing treatment/monitoring, such as glaucoma, which is not adequately controlled with medication or surgery, wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, presence of papilledema, an ocular condition with high risk of retinal detachment
6. Monocular vision with visual acuity in the worse-seeing eye (worse than 20/200 or visual fields less than 20 degrees)
6. Serious concurrent illness or clinically relevant active infection.
7. A history of multiple sclerosis or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome)
8. Participants with clinically significant cardiac disease.
9. A history of hemorrhagic or ischemic stroke within 6 months before enrollment
10. A history of cirrhotic liver disease (Child-Pugh Class B or C)
11. Participants with evidence of pneumonitis on baseline imaging or Participants with a previous clinical diagnosis of noninfectious interstitial lung disease (ILD), including noninfectious pneumonitis
12. Participants with prior hypersensitivity to monoclonal antibodies (mAb)
13. Females who are pregnant or breastfeeding
14. For Dose Optimization and Expansion Phase: Participants who received a prior FRα-targeting agent, with the exception of participants enrolled in the prior FRα-targeting agent, ovarian cancer cohort (Cohort C).
15. Untreated or symptomatic central nervous system metastases
16. A history of other malignancy within 3 years before enrollment

Contacts and Locations

Study Contact

ImmunoGen, Inc.

CONTACT

781-895-0600

medicalinformation@immunogen.com

Eric Westin, MD

CONTACT

781-895-0646

Eric.Westin@immunogen.com

Principal Investigator

Medical Director

STUDY_DIRECTOR

ImmunoGen, Inc.

Study Locations (Sites)

City of Hope

Irvine, California, 92618

United States

UCLA

Los Angeles, California, 90095

United States

University of Colorado Anschutz Cancer Pavilion

Aurora, Colorado, 80045

United States

Florida Cancer Specialists

Sarasota, Florida, 34232

United States

Karmanos Cancer Institute

Detroit, Michigan, 48201

United States

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14203

United States

OU Health Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104

United States

Tennessee Oncology Nashville

Nashville, Tennessee, 37203

United States

MD Anderson Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: ImmunoGen, Inc.

Medical Director, STUDY_DIRECTOR, ImmunoGen, Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-01-11

Study Completion Date2025-12-30

Study Record Updates

Study Start Date2023-01-11

Study Completion Date2025-12-30

Terms related to this study

Keywords Provided by Researchers

Antibody Drug Conjugate
Platinum-Resistant
Recurrent

Additional Relevant MeSH Terms

Endometrial Cancer
High Grade Serous Adenocarcinoma of Ovary
Primary Peritoneal Carcinoma
Fallopian Tube Cancer
Cervical Cancer