First in Human Study of IMGN151 in Recurrent Gynaecological Cancers

Phase 1

Recruiting

• Conditions: Endometrial Cancer; High Grade Serous Adenocarcinoma of Ovary; Primary Peritoneal Carcinoma; Fallopian Tube Cancer; Cervical Cancer
• Interventions: Drug: IMGN151

• Registration Number: NCT05527184
• Lead Sponsor: AbbVie

Brief Summary

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.

Detailed Description

Participants may continue on study drug based on clinical benefit until disease progression, adverse event (AE) requiring discontinuation, withdrawal of consent, physician decision, or other discontinuation criteria are met.

Study Timeline

• Study First Submitted: 2022-08-23
• Study First Submitted QC: 2022-09-01
• Study First Posted: 2022-09-02
• Study Start: 2023-01-11
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-21
• Last Update Posted: 2025-05-23
• Primary Completion: 2027-02
• Study Completion: 2027-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 423

Inclusion 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: Platinum-resistant, high-grade serous EOC (PROC) with no previous folate receptor alpha (FRα)-directed therapy. Participants with PROC will have had no more than 5 prior lines of therapy, with no more than 2 prior therapies since development of platinum resistance.

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, EOC of one of 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 cervical cancer with Combined Positive Score (CPS) > 1 or with endometrial cancer, 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.

Exclusion Criteria

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, defined as disease progression on or within 3 months completion 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
IMGN151	IMGN151	IMGN151 is administered via intravenous (IV) infusion on Day 1 of Cycle 1 every 3-week cycle (Q3W).

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Up to approximately 3 years
Number of Participants With Dose-limiting Toxicities (DLTs)	Day 21 of Cycle 1 (Cycle length = 3 weeks)
Recommended Dose of IMGN151 Monotherapy	Up to approximately 2 years

Secondary Outcome Measures

Name	Time	Method
Maximum Observed Plasma Concentration (Cmax) of IMGN151	Up to approximately 3 years
Time to Reach Cmax (Tmax) of IMGN151	Up to approximately 3 years
Area Under the Curve From Time 0 to Infinity (AUC0-inf) of IMGN151	Up to approximately 3 years
Number of Participants With Treatment-emergent Anti-drug Antibodies (ADAs)	Up to approximately 3 years
Objective Response Rate (ORR)	Up to approximately 3 years	ORR is defined as the percentage of participants with best response of complete response (CR) or partial response (PR) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
Duration of Response (DOR)	Up to approximately 3 years	DOR is defined as the time from initial response (CR or PR) until radiological progressive disease (PD), as assessed by the investigator, or death, whichever occurs first per RECIST v1.1 criteria.

Trial Locations

Locations (19)

University of Alabama at Birmingham /ID# 269045; 🇺🇸 Birmingham, Alabama, United States

City of Hope National Medical Center /ID# 269036; 🇺🇸 Duarte, California, United States

Moores Cancer Center /ID# 269040; 🇺🇸 La Jolla, California, United States

University of California Los Angeles Medical Center /ID# 269037; 🇺🇸 Los Angeles, California, United States

UCHSC Anschultz Cancer Pavilion /ID# 269056; 🇺🇸 Aurora, Colorado, United States

Mount Sinai Medical Center /ID# 269050; 🇺🇸 Miami, Florida, United States

Miami Cancer Institute at Baptist Health /ID# 269041; 🇺🇸 Miami, Florida, United States

Florida Cancer Specialists- Sarasota Cattlemen /ID# 269055; 🇺🇸 Sarasota, Florida, United States

Karmanos Cancer Institute - Detroit /ID# 269052; 🇺🇸 Detroit, Michigan, United States

Holy Name Medical Center /ID# 269051; 🇺🇸 Teaneck, New Jersey, United States

Roswell Park Cancer Institute /ID# 269043; 🇺🇸 Buffalo, New York, United States

Long Island Jewish Medical Center /ID# 269035; 🇺🇸 New Hyde Park, New York, United States

Columbia University Irving Medical Center /ID# 269033; 🇺🇸 New York, New York, United States

The Ohio State University Comprehensive Cancer Center /ID# 269026; 🇺🇸 Columbus, Ohio, United States

Ou Health - Stephenson Cancer Center /ID# 269025; 🇺🇸 Oklahoma City, Oklahoma, United States

University of Pennsylvania /ID# 269042; 🇺🇸 Philadelphia, Pennsylvania, United States

Women & Infants Hospital /ID# 269032; 🇺🇸 Providence, Rhode Island, United States

Tennessee Oncology Nashville /ID# 269029; 🇺🇸 Nashville, Tennessee, United States

MD Anderson Houston /ID# 269057; 🇺🇸 Houston, Texas, United States