Clinical Trials /

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

NCT04622774

Description:

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

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Non-Squamous Non-Small Cell Lung Carcinoma
  • Pancreatic Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: First-in-Human Study of IMGC936 in Patients With Advanced Solid Tumors
  • Official Title: A Phase 1, First-in-Human, Open-Label, Dose-Escalation Study of IMGC936 (Anti-ADAM9 Antibody Drug Conjugate) in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: IMGC936-0901
  • NCT ID: NCT04622774

Conditions

  • Advanced Solid Tumor

Interventions

DrugSynonymsArms
IMGC936IMGC936

Purpose

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

Detailed Description

      This is an open label, dose escalation 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.

      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. Infusion duration
      will vary depending on dose and participant tolerability. Sentinel dosing will be used for
      the first 2 dose levels. 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) for the first 6 months 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 even 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.
    

Trial Arms

NameTypeDescriptionInterventions
IMGC936ExperimentalSingle-arm. IMGC936 administered every 3 weeks.
  • IMGC936

Eligibility Criteria

        Inclusion Criteria:

          1. 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.

          2. Either measurable or non-measurable disease per RECIST 1.1 and documented by computed
             tomography (CT) and/or magnetic resonance imaging (MRI) obtained during screening.

          3. Age ≥ 18 years old.

          4. 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.

          5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          6. Life expectancy ≥ 12 weeks.

          7. Acceptable laboratory parameters as follows:

               -  Platelet count ≥ 75 × 1000/μL without transfusion within 28 days prior to
                  initiation 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.

               -  Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 3.0 × upper
                  limit of normal (ULN); for participants with hepatic metastases, ALT and AST ≤ 5
                  × ULN.

               -  Total bilirubin ≤ 1.5 × ULN, except participants with Gilbert's syndrome, who may
                  enroll if the conjugated bilirubin is within normal limits.

               -  Creatinine < 2 mg/dL, or a calculated creatinine clearance (based on the
                  Cockcroft-Gault formula) or measured creatinine clearance > 50 mL/min.

               -  Urinalysis protein ≤ 150 mg/d, red blood cells ≤ 2-5 per high powered field, and
                  white blood cells ≤ 2-5 per high powered field.

               -  Negative serum pregnancy test for females of childbearing potential (FOCBP).

          8. 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.

          9. 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.

         10. 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.

        Exclusion Criteria:

          1. Participants with history of prior central nervous system (CNS) metastasis must have
             been treated, must be asymptomatic, and must not have any of the following at the time
             of enrollment:

               -  No concurrent treatment for the CNS disease (e.g., surgery, radiation,
                  corticosteroids > 10 mg prednisone/day or equivalent).

               -  No progression of CNS metastases on MRI or CT for at least 21 days after last day
                  of prior therapy administered within the prior 6 months for the CNS metastases.

               -  No concurrent leptomeningeal disease or spinal cord compression.

          2. 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.

          3. Any investigational drug within 4 weeks prior to initiation of study drug.

          4. Participants must have completed prior therapy within the specified times below:

               -  Systemic antineoplastic therapy at least 5 half-lives or 4 weeks (whichever is
                  shorter) prior to initiation of study drug.

               -  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.

          5. Participants must have stabilized or recovered (Grade 1 or baseline) from all prior
             therapy-related toxicities (except alopecia).

          6. 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.

               -  Baseline left ventricular ejection fraction (LVEF) of < 50% by echocardiography
                  or multigated acquisition (MUGA) scan.

               -  QTcF or QTcB > 480 milliseconds calculated from the average of 3 repeat
                  electrocardiogram (ECGs) obtained at approximately 1-minute intervals.

          7. Clinically significant pulmonary compromise, including pneumonia, pneumonitis, or a
             requirement for supplemental oxygen use to maintain adequate oxygenation or history of
             ≥ Grade 3 drug-induced or radiation pneumonitis.

          8. 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).

               -  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.

          9. History of prior bone marrow, stem cell, or solid organ transplantation.

         10. 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.

         11. Major trauma or major surgery within 4 weeks prior to initiation of study drug.

         12. 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.

         13. Known hypersensitivity to ingredient or any excipient contained in the drug
             formulation

         14. Vaccination with any live virus vaccine within 4 weeks prior to initiation of study
             drug. Inactivated annual influenza vaccination is allowed.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To characterize safety and tolerability
Time Frame:From screening to end of study (approximately up to 2 years) for each patient
Safety Issue:
Description:Number of treatment emergent adverse events as assessed by CTCAE v5.0

Secondary Outcome Measures

Measure:To characterize study drug concentration
Time Frame:There are 9 blood draw collection time points at Cycles 1 and 3, 3 blood draw time points at Cycles 2,4,5 and 6, and collection at every 3 cycles after cycle 6 until end of study (approximately up to 2 years). Each cycle is 21 days.
Safety Issue:
Description:Study drug concentration
Measure:To characterize anti-drug antibody
Time Frame:There are 2 collection time points at Cycles 1 and 3, 1 collection time point at Cycles 2, 4, 5 and 6, and and collection at every 3 cycles after cycle 6 until end of study (approximately up to 2 years). Each cycle is 21 days.
Safety Issue:
Description:Anti-drug antibody

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:ImmunoGen, Inc.

Trial Keywords

  • Antibody Drug Conjugate
  • Phase 1
  • Solid Tumors

Last Updated

November 10, 2020