Clinical trial NCT05527184: First in Human Study of IMGN151 in Recurrent Gynaecological Cancers
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Endometrial Cancer
High Grade Serous Adenocarcinoma of Ovary
Primary Peritoneal Carcinoma
Fallopian Tube Cancer
Cervical Cancer
Keywords: Antibody Drug Conjugate
Platinum-Resistant
Recurrent
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2022-09-02
Enrollment: 423
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to approximately 3 years
measure: Number of Participants With Dose-limiting Toxicities (DLTs)
timeFrame: Day 21 of Cycle 1 (Cycle length = 3 weeks)
measure: Recommended Dose of IMGN151 Monotherapy
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of IMGN151
timeFrame: Up to approximately 3 years
measure: Time to Reach Cmax (Tmax) of IMGN151
timeFrame: Up to approximately 3 years
measure: Area Under the Curve From Time 0 to Infinity (AUC0-inf) of IMGN151
timeFrame: Up to approximately 3 years
measure: Number of Participants With Treatment-emergent Anti-drug Antibodies (ADAs)
timeFrame: Up to approximately 3 years
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 3 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 3 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham /ID# 269045
state: Alabama
city: Duarte
country: United States
facility: City of Hope National Medical Center /ID# 269036
state: California
city: La Jolla
country: United States
facility: Moores Cancer Center /ID# 269040
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles Medical Center /ID# 269037
state: California
city: Aurora
country: United States
facility: UCHSC Anschultz Cancer Pavilion /ID# 269056
state: Colorado
city: Kissimmee
country: United States
facility: AdventHealth Celebration /ID# 269030
state: Florida
city: Miami
country: United States
facility: Mount Sinai Medical Center /ID# 269050
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute at Baptist Health /ID# 269041
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists- Sarasota Cattlemen /ID# 269055
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medical Center /ID# 269028
state: Illinois
city: Boston
country: United States
facility: Dana-Farber Cancer Institute /ID# 269039
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute - Detroit /ID# 269052
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Cancer Center /ID# 269046
state: Mississippi
city: Teaneck
country: United States
facility: Holy Name Medical Center /ID# 269051
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute /ID# 269043
state: New York
city: New Hyde Park
country: United States
facility: Long Island Jewish Medical Center /ID# 269035
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center /ID# 269033
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Medical Center /ID# 269027
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center /ID# 269026
state: Ohio
city: Oklahoma City
country: United States
facility: Ou Health - Stephenson Cancer Center /ID# 269025
state: Oklahoma
city: Philadelphia
country: United States
facility: University of Pennsylvania /ID# 269042
state: Pennsylvania
city: Pittsburgh
country: United States
facility: West Penn Hospital /ID# 269054
state: Pennsylvania
city: Providence
country: United States
facility: Women & Infants Hospital /ID# 269032
state: Rhode Island
city: Nashville
country: United States
facility: Tennessee Oncology Nashville /ID# 269029
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Houston /ID# 269057
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia /ID# 269053
state: Virginia
city: Kelowna
country: Canada
facility: BC Cancer - Kelowna /ID# 268983
state: British Columbia
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: