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

Study Identifier:
IMGN151-1001
CT.gov Identifier:
NCT05527184
EudraCT Identifier:
2023-506842-22
EU Trial (CTIS) Number:
2023-506842-22-00
Study Contact Information:
(210) 593-5651 or [email protected]
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Study Summary

To evaluate IMGN151 in patients with cancer. To evaluate the safety, tolerability, PK, immunogenicity, and preliminary antitumor activity of IMGN151 in patients with recurrent endometrial cancer, or recurrent, high-grade serous epithelial ovarian cancer, primary peritoneal, or fallopian tube cancers 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 the recommended dose of IMGN151 monotherapy

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Endometrial
  • Ovarian
  • Primary Peritoneal
  • Fallopian Tube
  • Cervical cancer
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female
    Age
    18+ years
    Study Drug
  • Drug: Experimental: IMGN151 Open Label
    • Read More
  • Drug: All patients in the escalation phase will be assigned sequentially to one of up to eight doses in a 3+3 design. Once the recommended Phase 2 dose is identified, an expansion phase of the study will enroll patients into cohorts of either endometrial cancer or platinum-resistant ovarian cancer. DuringEscalation IMGN151 is administered via intravenous (IV) infusionon Day 1 ofCycle 1 andeverysubsequent 21-day cycle thereafter, at theassigneddosefor each cohort during dose escalationandat the RP2D for expansion. Infusion duration will vary depending on dose and participant tolerability.
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruiting

    Requirements information
    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 FR-targeting agent, with the exception of participants enrolled in the prior FR-targeting agent, ovarian cancer cohort (Cohort C).
    • Untreated or symptomatic central nervous system metastases
    • A history of other malignancy within 3 years before enrollment

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Dublin
    Dublin, Ireland, D07 R2WY
    Investigator
    Austin Duffy
    Status
    Recruiting
    Condition(s) Treated at Site
    Endometrial
    Ovarian
    Primary Peritoneal
    Fallopian Tube
    Cervical cancer