Endometrial Cancer, High Grade Serous Adenocarcinoma of Ovary, Primary Peritoneal Carcinoma, Fallopian Tube Cancer, Cervical Cancer
Conditions
Keywords
Antibody Drug Conjugate, Platinum-Resistant, Recurrent
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.
Interventions
DRUGIMGN151
IMGN151 is an antibody-drug conjugate (ADC).
Sponsors
AbbVie
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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 Grade 3 endometrioid or serous histology only) with 1-3 prior lines of therapy. 2. For Cohort B, a confirmed diagnosis of high-grade serous 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, a confirmed diagnosis of high-grade serous PROC with previous FRα-directed therapy with at least one intervening anticancer therapy between prior FRα-directed therapy other than mirvetuximab soravtansine. 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 serous or high-grade Grade 3 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. Note: medication management to achieve Grade 1 (asymptomatic) is acceptable. 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 (including transient ischemic attack) 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). Receipt of prior mirvetuximab soravtansine is excluded for all cohorts. 15. Untreated or symptomatic central nervous system metastases 16. A history of other malignancy within 3 years before enrollment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Australia, Belgium, Canada, France, Germany, Ireland, Italy, Netherlands, Spain, United States
Contacts
STUDY_DIRECTORABBVIE INC.
AbbVie
Outcome results
None listed