First in Human Study of IMGN151 in Recurrent Gynaecological Cancers

Launched by ABBVIE · Sep 1, 2022

Keywords

ClinConnect Summary

This clinical trial, called IMGN151-1001, is testing a new treatment called IMGN151 for women with certain types of recurrent cancers, specifically endometrial cancer and high-grade ovarian, peritoneal, or fallopian tube cancers. The trial is currently recruiting participants aged 18 and older who have had previous cancer treatments and are still experiencing cancer progression. To qualify, participants should have a good level of physical functioning and should not have certain other health issues.

Participants in this study can expect to receive the new drug IMGN151, which is being tested for safety and effectiveness. The trial is designed to find the right dose and to see how well the treatment works. All patients will receive the treatment openly, meaning everyone knows they are getting IMGN151. It's important for potential participants to understand that they will need to provide previous medical information and might need a biopsy for testing. Additionally, women who can become pregnant must use effective birth control during the trial and for three months after stopping treatment. This trial is an opportunity to contribute to the understanding of new cancer therapies, and participants will be closely monitored throughout the study.

Gender

FEMALE

Eligibility criteria

• 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