A Phase 1, First-in-Human, Open-Label, Dose-Escalation and Expansion Study of IMGN151 (anti-FRa antibody-drug conjugate) in Adult Patients with Recurrent Endometrial Cancer and Recurrent, High-Grade Recurrent Endometrial Cancer and Recurrent, High-Grade Serous Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers

Cancer Categories

Gynecologic

Karmanos Trial ID

2024-029

NCT ID

NCT05527184

Age Group

Adult

Scope

National

Phase

Phase I

Principal Investigator

Ira
Winer, M.D., Ph.D., FACOG
Oncology - Gynecologic, Oncology - Surgical View Profile

Objective:

Dose-Escalation Phase

Co-Primary Objectives:

To assess safety and tolerability, including dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), or maximum administered dose (MAD; if no MTD is defined) of IMGN151 when administered intravenously
To determine recommended Phase 2 dose (RP2D) for IMGN151

Secondary Objectives:

To characterize the pharmacokinetics (PK) and immunogenicity of IMGN151
To assess objective response rate (ORR) for IMGN151 using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
To assess duration of response (DOR) for IMGN151 using RECIST v1.1

Expansion Phase

Primary Objective:

To assess ORR for IMGN151 using RECIST v1.1

Secondary Objectives:

To characterize safety and tolerability for IMGN151
To characterize the PK and immunogenicity of IMGN151
To assess DOR for IMGN151
To assess PFS for IMGN151

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Eligibility

Inclusion Criteria:

Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
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.
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.
Expansion Phase:

For Cohort A, recurrent endometrial cancer (high-grade endometrioid or serous histology only) with 1-3 prior lines of therapy.
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.
For Cohort C, PROC with previous FRα-directed therapy with at least one intervening anticancer therapy between prior FRα-directed therapy and IMGN151.
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.
For Cohort E, cervical cancer including the following histologies: squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma with 1-4 prior lines of therapy.
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.

Evaluable lesions

Dose-Escalation Phase: Participants may have radiologically evaluable or nonevaluable disease.
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).

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.
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).
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.
Participants must have adequate organ and bone marrow function.

Exclusion Criteria:

Participants with ovarian cancer with histologies including clear cell, mucinous, or borderline ovarian tumor.

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.
For Cohort A, participants with endometrial cancer with histologies other than high-grade serous or high-grade endometrioid.
For Cohort E, participants with cervical cancer with histologies other than adenocarcinoma, squamous cell carcinoma, and adenosquamous carcinoma.

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.
Radiation therapy of > 20% of the potential bone marrow
Participants with > Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Participants with the following ocular history and/or concurrent disorders:

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
History of corneal transplantation
Undergoing active postoperative management for refractive surgery, cataract surgery, corneal cross-linking, or corneal complications of surgery
Active or chronic clinically significant (≥ Grade 3) corneal disorders (for example, Fuch's dystrophy or neurotrophic keratitis)
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
Monocular vision with visual acuity in the worse-seeing eye (worse than 20/200 or visual fields less than 20 degrees)

Serious concurrent illness or clinically relevant active infection.
A history of multiple sclerosis or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome)
Participants with clinically significant cardiac disease.
A history of hemorrhagic or ischemic stroke within 6 months before enrollment
A history of cirrhotic liver disease (Child-Pugh Class B or C)
Participants with evidence of pneumonitis on baseline imaging or Participants with a previous clinical diagnosis of noninfectious interstitial lung disease (ILD), including noninfectious pneumonitis
Participants with prior hypersensitivity to monoclonal antibodies (mAb)
Females who are pregnant or breastfeeding
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).
Untreated or symptomatic central nervous system metastases

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Detroit, MI 48201
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Phone: 1-800-527-6266

Karmanos Cancer Institute at Weisberg Cancer Center - Farmington Hills

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Farmington Hills, MI 48334
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Phone: 1-800-527-6266

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