First-in-Human Study of IMGC936 in Patients With Advanced Solid Tumors

  • STATUS
    Recruiting
  • End date
    Apr 30, 2024
  • participants needed
    245
  • sponsor
    ImmunoGen, Inc.
Updated on 13 July 2022

Summary

This study is a Phase 1/2, first-in-human, open-label, dose-escalation, and expansion study designed to characterize the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary antitumor activity of IMGC936 administered by intravenous (IV) infusion.

Description

This is an open-label, dose-escalation, and expansion study to determine the Maximum Tolerated Dose (MTD) and select the recommended phase 2 dose. Dose escalation follows a conventional 3+3 design; successive cohorts of 3 to 6 participants each will be evaluated in sequential escalating doses of single-agent IMGC936. Upon completion of the dose-escalation phase of the study, following determination of the recommended Phase 2 dose (RP2D), up to 5 expansion cohorts may be opened in tumor types selected from those enrolled in dose escalation.

Participants with relapsed or refractory, unresectable locally advanced or metastatic solid tumors including non-squamous non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), colorectal cancer (CRC), gastroesophageal cancer, or pancreatic cancer will be enrolled.

IMGC936 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.

Sentinel dosing will be used for the first 2 dose levels of dose escalation. The first administration of IMGC936 in participants at the first 2 dose levels of dose escalation will be staggered by at least 48 hours. The dose-limiting toxicity (DLT) evaluation period is 21 days. Participants may continue on study drug until disease progression, adverse event (AE) requiring discontinuation, DLT during evaluation window, pregnancy, death, investigator decision, lost to follow up (LTFU), major protocol deviation requiring discontinuation, withdrawal of consent, or sponsor, investigator or regulatory agency terminates the study.

Tumor assessments are performed every 6 weeks (Q6W) while on study drug then every 12 weeks (Q12W). Tumor assessments continue until discontinuation criteria are met. If feasible, participants who discontinue study drug for reasons other than progressive disease (PD) (e.g., toxicity) should continue to undergo tumor assessments Q12W as post-treatment follow up until evidence of PD, initiation of another anticancer therapy, withdrawal of consent, LTFU, death, or end of study. Post-treatment follow up also includes following ongoing treatment emergent adverse events (TEAEs) until the event has resolved to baseline grade, the event is assessed by the investigator as stable, initiations of another anticancer therapy, withdrawal of consent, LTFU, death, or it has been determined that study drug or participation is not the cause of the AE.

Details
Condition Advanced Solid Tumor
Treatment IMGC936
Clinical Study IdentifierNCT04622774
SponsorImmunoGen, Inc.
Last Modified on13 July 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Participants with histologically proven, relapsed or refractory, unresectable locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), colorectal cancer (CRC), gastroesophageal cancer, or pancreatic cancer for whom no therapy with demonstrated clinical benefit is available
NSCLC: Participants must have been treated with 1 to 4 prior lines of systemic therapy with no more than 2 chemotherapy containing lines
TNBC: Participants must have been treated with 1 to 4 prior lines of systemic therapy for metastatic disease, excluding adjuvant therapies
CRC: Participants must have been treated with 1 to 3 prior lines of systemic therapy
Archival formalin-fixed paraffin-embedded (FFPE) tissue must be available. Participants may undergo a fresh tumor biopsy using a low risk, medically routine procedure to obtain a specimen for testing if a tumor sample is not available
Gastroesophageal cancer: Participants must have been treated with 1 to 3 prior lines of systemic therapy
Pancreatic cancer: Participants must have been treated with 1 to 3 prior lines of systemic therapy, with no more than 2 chemotherapy containing lines
Either measurable or non-measurable disease per RECIST 1.1 and documented by computed
Acceptable laboratory parameters as follows
tomography (CT) and/or magnetic resonance imaging (MRI) obtained within 28
Dose escalation: Participants may have non-measurable or measurable disease
Dose expansion: Participants must have measurable disease
days of C1D1
Age ≥ 18 years old
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. If ECOG performance status is an inappropriate performance measurement for participant enrollment (eg, chronically non-ambulatory), then Karnofsky performance status must be ≥ 70
Negative serum pregnancy test for females of childbearing potential (FOCBP)
Life expectancy ≥ 12 weeks
FOCBP and male participants with partners of FOCBP must agree to use highly effective methods of contraception, from the time of consent through 28 weeks after discontinuation of study drug administration. Male participants must abstain from sperm donation during the study
Platelet count ≥ 75 × 1000/μL without transfusion within 28 days prior to initiation of study drug
FOCBP is not pregnant or breastfeeding, or a male participant is not expecting to father children within the projected duration of the study, starting with screening visit through 28 weeks after the last dose of study drug
Absolute neutrophil count ≥ 1.5 × 1000/μL in the absence of any growth factor support within 21days prior to initiation of study drug
Estimated glomerular filtration rate (eGFR) >30mL/min/1.73m2 or an estimated creatinine clearance of >30 mL/min
Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 3.0 × upper limit of normal (ULN); for participants with hepatic metastases, ALT and AST ≤ 5 × ULN
Urinalysis protein and white occult blood cells within normal limits
Total bilirubin ≤ 1.5 × ULN, except participants with Gilbert's syndrome, who may enroll if the conjugated bilirubin is within normal limits
FOCBP, defined as not surgically sterilized (hysterectomy, bilateral salpingectomy
and bilateral oophorectomy) and between menarche and 1-year post menopause
must have a negative serum pregnancy test performed within 72 hours prior to
initiation of study drug administration. Female participants must abstain from
egg donation during the study

Exclusion Criteria

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
Systemic antineoplastic therapy at least 5 half-lives or 4 weeks (whichever is shorter) prior to initiation of study drug
Active central nervous system (CNS) disease within the last 6 months
Mediastinal or pelvic radiation therapy within 6 weeks prior to initiation of study drug administration. Palliative, limited field radiation for symptom control to soft tissues, or bone lesions within 2 weeks prior to initiation of study drug
Participants who had prior therapies within the specified times below
Clinically significant cardiovascular disease including but not limited to
Myocardial infarction or unstable angina within 6 months prior to initiation of study drug
Stroke or transient ischemic attack within 6 months prior to initiation of study drug
Current clinically significant cardiac arrhythmias, e.g., atrial fibrillation that are not well controlled with optimal medical intervention
Current uncontrolled hypertension: systolic blood pressure > 160 mmHg, diastolic blood pressure > 100 mmHg
Current congestive heart failure (New York Heart Association class III-IV)
Current pericarditis or clinically significant pericardial effusion
Current myocarditis
Participants must have stabilized or recovered (Grade 1 or baseline) from all prior
therapy-related toxicities (except alopecia)
Left ventricular ejection fraction (LVEF) of < 50% by scan
Serious concurrent illness or clinically relevant active infection, including, but not limited to the following
QTc interval > 480 msec
Active hepatitis B or C infection (whether or not on active antiviral therapy)
Human immunodeficiency virus infection
Cytomegalovirus infection
Active COVID-19/SARS-CoV-2 infection. While SARS-CoV-2 testing is not mandatory for study entry, testing should follow local clinical practice guidelines/standards
Any other concurrent infectious disease requiring IV antibiotics within 2 weeks prior to initiation of study drug
History of prior bone marrow, stem cell, or solid organ transplantation
Second primary invasive malignancy that has not been in remission for greater than 2 years except nonmelanoma skin cancer; cervical carcinoma in situ on biopsy; or squamous intraepithelial lesion on Pap smear; localized prostate cancer (Gleason score < 6); or resected melanoma in situ
Major trauma or major surgery within 4 weeks prior to initiation of study drug
Any serious underlying medical or psychiatric condition that would impair the ability of the participant to receive or tolerate the planned treatment at the study site
Clinically significant pulmonary compromise, including pneumonia, pneumonitis, or a
requirement for supplemental oxygen (excluding for sleep apnea) or history of
Vaccination with any live virus vaccine within 4 weeks prior to initiation of study drug. Inactivated annual influenza vaccination is allowed
≥ Grade 3 drug-induced or radiation pneumonitis
Known hypersensitivity to any ingredient or any excipient contained in the drug formulation
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