Trial Title:
First in Human Study of IMGN151 in Recurrent Endometrial Cancer and Recurrent, High-grade Serous Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers
NCT ID:
NCT05527184
Condition:
Endometrial Cancer
High Grade Serous Adenocarcinoma of Ovary
Primary Peritoneal Carcinoma
Fallopian Tube Cancer
Conditions: Official terms:
Endometrial Neoplasms
Fallopian Tube Neoplasms
Cystadenocarcinoma, Serous
Conditions: Keywords:
Antibody Drug Conjugate
Platinum-Resistant
Recurrent
Phase 1/2
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Intervention model description:
Open-label dose escalation study with dosing every three weeks. 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. During EscalationIMGN151 is administered via intravenous (IV) infusion on
Day 1 of Cycle 1 and every subsequent 21-day cycle thereafter, at the assigned dose for
each cohort during dose escalation and at the RP2D for expansion. Infusion duration will
vary depending on dose and participant tolerability.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
IMGN151
Description:
IMGN151 is an antibody-drug conjugate (ADC).
Arm group label:
IMGN151 Open Label
Summary:
IMGN151-1001 is a Phase 1, first in human, open-label dose-escalation and expansion study
in adult patients with recurrent endometrial cancer, recurrent, high-grade serous
epithelial ovarian, primary peritoneal, or fallopian tube cancers.
Detailed description:
This Phase 1 study is designed to characterize 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. All patients will be, in the opinion of the
investigator, appropriate for nonplatinum single-agent therapy for their next line of
therapy.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients ≥ 18 years of age
2. Patients must have an Eastern Cooperative Oncology Group Performance Status (ECOG
PS) of 0 or 1.
3. Dose-Escalation Phase: Patients must have a confirmed diagnosis of recurrent
endometrial cancer or high-grade serous epithelial ovarian cancer (EOC), primary
peritoneal, or fallopian tube cancer.
4. Expansion Phase: Patients must have a confirmed diagnosis of recurrent endometrial
cancer or platinum-resistant, high-grade serous epithelial ovarian cancer (PROC),
primary peritoneal, or fallopian tube cancer.
Note: Progression should be calculated from the date of the last administered dose
of platinum therapy to the date of the radiographic imaging showing progression.
5. Prior anticancer therapy
1. For Expansion Phase: Patients must have recurrent endometrial cancer or
patients with PROC must have received 1-4 prior systemic lines of therapy.
2. Neoadjuvant ± adjuvant therapies are considered 1 line of therapy.
3. Maintenance therapy (eg, bevacizumab or poly [ADP-ribose] polymerase [PARP]
inhibitors) will be considered part of the preceding line of therapy (ie, not
counted independently).
4. Therapy changed due to toxicity in the absence of progression will be
considered part of the same line (ie, not counted independently).
5. Hormonal therapy will be counted as a separate line of therapy unless it was
given as maintenance.
6. Evaluable lesions
1. Dose-Escalation Phase: Patients may have radiologically evaluable or
nonevaluable disease.
2. Expansion Phase: Patients must have at least 1 lesion that meets the definition
of measurable disease by RECIST v1.1 (radiologically measured by the
investigator).
7. Patients must be 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 for retrospective IHC confirmation of FRα status.
8. Patients must have completed prior therapy within the specified times below:
1. Systemic antineoplastic therapy within 5 half-lives or 4 weeks (whichever is
shorter) before the first dose of IMGN151
2. Focal radiation completed at least 2 weeks before the first dose of IMGN151
9. Patients must have stabilized or recovered (Grade 1 or baseline) from all prior
therapy-related toxicities (except alopecia).
10. Patients must have completed any major surgery at least 4 weeks before the first
dose of IMGN151 and have recovered or stabilized from the side effects of prior
surgery before the first dose of IMGN151.
11. Patients must have adequate hematologic, liver, and kidney functions defined as
follows:
1. Absolute neutrophil count (ANC) ≥ 1.5 ×10 9/L (1500/μL) without granulocyte
colony-stimulating factor (G-CSF) in the prior 10 days or long-acting white
blood cell growth factors in the prior 20 days
2. Platelet count ≥ 100 × 10 9/L (100,000/μL) without platelet transfusion in the
prior 10 days
3. Hemoglobin ≥ 9.0 g/dL without packed red blood cell transfusion in the prior 21
days
4. Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 or an estimated
creatinine clearance of ≥ 60 mL/min
5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 ×
upper limit of normal (ULN)
6. Serum bilirubin ≤ 1.5 × ULN (patients with documented diagnosis of Gilbert
syndrome are eligible if total bilirubin < 3.0 × ULN)
7. Serum albumin ≥ 2 g/dL
12. Patients must be willing and able to sign the informed consent form (ICF) and to
adhere to the protocol requirements.
13. Females of childbearing potential (FOCBP) must agree to use highly effective
contraceptive method(s) while on IMGN151 and for at least 3 months after the last
dose.
14. FOCBP must have a negative serum pregnancy test at Screening and a negative serum or
urine pregnancy test within 72 hours before the first dose of IMGN151.
Exclusion Criteria:
1. Patients with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed
tumors containing any of the above histologies, or low-grade/borderline ovarian
tumor
2. Patients with prior wide-field radiotherapy affecting at least 20% of the bone
marrow
3. Patients with > Grade 1 peripheral neuropathy per CTCAE v5.0
4. Patients with active or chronic corneal disorders, history of corneal
transplantation, or active ocular conditions requiring ongoing treatment/monitoring,
such as uncontrolled glaucoma, wet age-related macular degeneration requiring
intravitreal injections, active diabetic retinopathy with macular edema, macular
degeneration, presence of papilledema, and/or monocular vision
5. Patients with serious concurrent illness or clinically relevant active infection,
including, but not limited to the following:
1. Active hepatitis B or C infection (whether or not on active antiviral therapy)
2. HIV infection in patients with CD4+ T-cell (CD4+) counts < 350 cells/µL
3. Active cytomegalovirus infection
4. Active COVID-19/SARS-CoV-2 infection. Although SARS-CoV-2 testing is not
mandatory for study entry, testing should follow local clinical practice
guidelines and standards
5. Any other concurrent infectious disease requiring IV antibiotics within 2 weeks
before the first dose of IMGN151 Note: Testing at Screening is not required for
the above infections unless clinically indicated.
6. Patients with a history of multiple sclerosis or other demyelinating disease and/or
Lambert-Eaton syndrome (paraneoplastic syndrome)
7. Patients with clinically significant cardiac disease including, but not limited to,
any of the following:
1. Myocardial infarction ≤ 6 months before the first dose
2. Unstable angina pectoris
3. Uncontrolled congestive heart failure (New York Heart Association > class II)
4. Uncontrolled ≥ Grade 3 hypertension (per CTCAE v5.0)
5. Uncontrolled cardiac arrhythmias
6. QTc interval > 470 ms
8. Patients with a history of hemorrhagic or ischemic stroke within 6 months before
enrollment
9. Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C)
10. Patients with evidence of pneumonitis on baseline imaging or patients with a
previous clinical diagnosis of noninfectious interstitial lung disease (ILD),
including noninfectious pneumonitis
11. Patients requiring use of folate-containing supplements (eg, folate deficiency)
12. Patients with prior hypersensitivity to monoclonal antibodies (mAb)
13. Females who are pregnant or breastfeeding
14. For Expansion Phase: Patients who received a prior FRα-targeting agent
15. Patients with untreated or symptomatic central nervous system metastases
16. Patients with a history of other malignancy within 3 years before enrollment Note:
Patients with tumors with a negligible risk for metastasis or death (eg, adequately
controlled basal-cell carcinoma or squamous-cell carcinoma of the skin, or carcinoma
in situ of the cervix or breast) are eligible.
17. Prior known hypersensitivity reactions to study drugs and/or any of their excipients
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope
Address:
City:
Irvine
Zip:
92618
Country:
United States
Status:
Recruiting
Contact:
Last name:
Joshua Cohen
Phone:
626-221-2036
Email:
JGCohen@coh.org
Facility:
Name:
UCLA
Address:
City:
Los Angeles
Zip:
90095
Country:
United States
Status:
Recruiting
Contact:
Last name:
Gottfried Konecny, MD
Phone:
310-794-4955
Email:
GKonecny@mednet.ucla.edu
Facility:
Name:
University of Colorado Anschutz Cancer Pavilion
Address:
City:
Aurora
Zip:
80045
Country:
United States
Status:
Recruiting
Contact:
Last name:
Bradley R Corr, MD
Phone:
303-234-1067
Email:
BRADLEY.CORR@CUANSCHUTZ.EDU
Facility:
Name:
Florida Cancer Specialists
Address:
City:
Sarasota
Zip:
34232
Country:
United States
Status:
Recruiting
Contact:
Last name:
Judy Wang, MD
Phone:
914-377-9993
Email:
jswang@flcancer.com
Facility:
Name:
Karmanos Cancer Institute
Address:
City:
Detroit
Zip:
48201
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ira Winer
Phone:
313-576-9435
Email:
iwiner@med.wayne.edu
Facility:
Name:
Roswell Park Comprehensive Cancer Center
Address:
City:
Buffalo
Zip:
14203
Country:
United States
Status:
Recruiting
Contact:
Last name:
Emese Zsiros
Phone:
716-845-8631
Email:
Emese.zsiros@roswellpark.org
Facility:
Name:
OU Health Stephenson Cancer Center
Address:
City:
Oklahoma City
Zip:
73104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kathleen Moore, MD
Phone:
405-271-8001
Email:
Kathleen-Moore@ouhsc.edu
Facility:
Name:
Tennessee Oncology Nashville
Address:
City:
Nashville
Zip:
37203
Country:
United States
Status:
Recruiting
Contact:
Last name:
Erika Hamilton, MD
Phone:
615-320-5090
Email:
ehamilton@tnonc.com
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Funda Meric-Bernstam, MD
Phone:
713-792-2848
Email:
fmeric@mdanderson.org
Start date:
January 11, 2023
Completion date:
December 30, 2025
Lead sponsor:
Agency:
ImmunoGen, Inc.
Agency class:
Industry
Source:
ImmunoGen, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05527184
