Open
Actively Recruiting
First in Human Study of IMGN151 in Recurrent Endometrial Cancer and Recurrent, High-grade Serous Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers
About
Brief 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.
Primary Purpose
Study Type
Phase
Eligibility
Gender
Healthy Volunteers
Minimum Age
Maximum Age
Inclusion Criteria:
- Patients ≥ 18 years of age
- Patients must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
- 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.
- 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.
- Prior anticancer therapy
- For Expansion Phase: Patients must have recurrent endometrial cancer or patients with PROC must have received 1-4 prior systemic lines of therapy.
- Neoadjuvant ± adjuvant therapies are considered 1 line of therapy.
- 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).
- Therapy changed due to toxicity in the absence of progression will be considered part of the same line (ie, not counted independently).
- Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance.
- Evaluable lesions
- Dose-Escalation Phase: Patients may have radiologically evaluable or nonevaluable disease.
- 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).
- 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.
- Patients must have completed prior therapy within the specified times below:
- Systemic antineoplastic therapy within 5 half-lives or 4 weeks (whichever is shorter) before the first dose of IMGN151
- Focal radiation completed at least 2 weeks before the first dose of IMGN151
- Patients must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia).
- 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.
- Patients must have adequate hematologic, liver, and kidney functions defined as follows:
- 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
- Platelet count ≥ 100 × 10 9/L (100,000/μL) without platelet transfusion in the prior 10 days
- Hemoglobin ≥ 9.0 g/dL without packed red blood cell transfusion in the prior 21 days
- Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 or an estimated creatinine clearance of ≥ 60 mL/min
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × upper limit of normal (ULN)
- Serum bilirubin ≤ 1.5 × ULN (patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin < 3.0 × ULN)
- Serum albumin ≥ 2 g/dL
- Patients must be willing and able to sign the informed consent form (ICF) and to adhere to the protocol requirements.
- 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.
- 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:
- Patients with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, or low-grade/borderline ovarian tumor
- Patients with prior wide-field radiotherapy affecting at least 20% of the bone marrow
- Patients with > Grade 1 peripheral neuropathy per CTCAE v5.0
- 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
- Patients with serious concurrent illness or clinically relevant active infection, including, but not limited to the following:
- Active hepatitis B or C infection (whether or not on active antiviral therapy)
- HIV infection in patients with CD4+ T-cell (CD4+) counts < 350 cells/µL
- Active cytomegalovirus infection
- 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
- 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.
- Patients with a history of multiple sclerosis or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome)
- Patients with clinically significant cardiac disease including, but not limited to, any of the following:
- Myocardial infarction ≤ 6 months before the first dose
- Unstable angina pectoris
- Uncontrolled congestive heart failure (New York Heart Association > class II)
- Uncontrolled ≥ Grade 3 hypertension (per CTCAE v5.0)
- Uncontrolled cardiac arrhythmias
- QTc interval > 470 ms
- Patients with a history of hemorrhagic or ischemic stroke within 6 months before enrollment
- Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C)
- Patients with evidence of pneumonitis on baseline imaging or patients with a previous clinical diagnosis of noninfectious interstitial lung disease (ILD), including noninfectious pneumonitis
- Patients requiring use of folate-containing supplements (eg, folate deficiency)
- Patients with prior hypersensitivity to monoclonal antibodies (mAb)
- Females who are pregnant or breastfeeding
- For Expansion Phase: Patients who received a prior FRα-targeting agent
- Patients with untreated or symptomatic central nervous system metastases
- 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.
- Prior known hypersensitivity reactions to study drugs and/or any of their excipients
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Study Stats
Protocol No.
22-001780
Category
Cervical Cancer
Colorectal Cancer
Other Cancer
Ovarian Cancer
Principal Investigator
Location
- UCLA Westwood