Clinical Trials /

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

NCT04622774

Description:

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.

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

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: First-in-Human Study of IMGC936 in Patients With Advanced Solid Tumors
  • Official Title: A Phase 1/2, First-in-Human, Open-Label, Dose-Escalation and Expansion 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 1/2, 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.

Detailed 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.
    

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.

               1. NSCLC: Participants must have been treated with 1 to 4 prior lines of systemic
                  therapy with no more than 2 chemotherapy containing lines.

               2. TNBC: Participants must have been treated with 1 to 4 prior lines of systemic
                  therapy for metastatic disease, excluding adjuvant therapies.

               3. CRC: Participants must have been treated with 1 to 3 prior lines of systemic
                  therapy.

               4. Gastroesophageal cancer: Participants must have been treated with 1 to 3 prior
                  lines of systemic therapy.

               5. Pancreatic cancer: Participants must have been treated with 1 to 3 prior lines of
                  systemic therapy, with no more than 2 chemotherapy containing lines.

          2. Either measurable or non-measurable disease per RECIST 1.1 and documented by computed
             tomography (CT) and/or magnetic resonance imaging (MRI) obtained within 28 days of
             C1D1.

               -  Dose escalation: Participants may have non-measurable or measurable disease

               -  Dose expansion: Participants must have measurable disease

          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. If ECOG
             performance status is an inappropriate performance measurement for participant
             enrollment (eg, chronically non-ambulatory), then Karnofsky performance status must be
             ≥ 70.

          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.

               -  Estimated glomerular filtration rate (eGFR) >30mL/min/1.73m2 or an estimated
                  creatinine clearance of >30 mL/min.

               -  Urinalysis protein and white occult blood cells within normal limits.

               -  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. Active central nervous system (CNS) disease within the last 6 months.

          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. Participants who had prior therapies 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.

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

          5. 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.

               -  Left ventricular ejection fraction (LVEF) of < 50% by scan

               -  QTc interval > 480 msec

          6. Clinically significant pulmonary compromise, including pneumonia, pneumonitis, or a
             requirement for supplemental oxygen (excluding for sleep apnea) or history of ≥ Grade
             3 drug-induced or radiation pneumonitis.

          7. 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.

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

          9. 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.

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

         11. 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.

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

         13. 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:During dose escalation measure incidence and severity of Treatment Emergent Adverse Events by CTCAE v5.0
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:During dose escalation and expansion 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:During dose escalation and expansion to measure the concentration of 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
Measure:During dose expansion describe the duration of response and progression free survival
Time Frame:From screening to end of study (approximately up to 2 years) for each patient
Safety Issue:
Description:Time to disease progression
Measure:During dose escalation to describe the objective response rate and duration of response
Time Frame:From screening to end of study (approximately up to 2 years) for each patient
Safety Issue:
Description:Time to disease progression
Measure:During dose expansion measure incidence and severity of Treatment Emergent Adverse Events by CTCAE v5.0
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

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:ImmunoGen, Inc.

Trial Keywords

  • Antibody Drug Conjugate
  • Phase 1/2
  • Solid Tumors

Last Updated

June 9, 2021