Clinical Trials /

Phase I Study of IGM-8444 as a Single Agent and in Combination in Subjects With Relapsed and/or Refractory Solid Cancers

NCT04553692

Description:

This study is a first-in-human, Phase 1, multicenter, open-label study to determine the safety, tolerability and pharmacokinetics of IGM-8444 as a single agent and in combination in subjects with relapsed and/or refractory solid cancers

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase I Study of IGM-8444 as a Single Agent and in Combination in Subjects With Relapsed and/or Refractory Solid Cancers
  • Official Title: An Open-label, Multicenter, Phase I Study of IGM-8444 as a Single Agent and in Combination in Subjects With Relapsed and/or Refractory Solid Cancers

Clinical Trial IDs

  • ORG STUDY ID: IGM-8444-001
  • NCT ID: NCT04553692

Conditions

  • Solid Tumor
  • Colorectal Cancer
  • Gastric Cancer
  • Non Hodgkin Lymphoma
  • Non-Small Cell Lung Cancer
  • Sarcoma
  • Chondrosarcoma
  • Small Lymphocytic Lymphoma
  • Chronic Lymphocytic Leukemia

Interventions

DrugSynonymsArms
IGM-8444IGM-8444 + Birinapant Escalation
FOLFIRIFluorouracil or 5-FU, Leucovorin, IrinotecanIGM-8444 + FOLFIRI + Bevacizumab (and approved biosimilars) Expansion
Bevacizumab (and approved biosimilars)AvastinIGM-8444 + FOLFIRI + Bevacizumab (and approved biosimilars) Expansion
BirinapantIGM-8444 + Birinapant Escalation
VenetoclaxVenclextaIGM-8444 + Venetoclax Escalation

Purpose

This study is a first-in-human, Phase 1, multicenter, open-label study to determine the safety, tolerability and pharmacokinetics of IGM-8444 as a single agent and in combination in subjects with relapsed and/or refractory solid cancers

Detailed Description

      Patients will be enrolled in two stages: a dose-escalation stage and an expansion stage.

      The escalation stage will investigate single agent IGM-8444 in patients with solid tumors,
      IGM-8444 in combination with FOLFIRI for colorectal carcinoma patients, IGM-8444 in
      combination with birinapant in patients with solid tumors, and IGM-8444 in combination with
      venetoclax in patients with CLL/SLL. The IGM-8444 single agent expansion cohort will enroll
      solid tumor patients and may include relapsed/refractory non-Hodgkin lymphoma patients. The
      IGM-8444 + FOLFIRI with or without bevacizumab combination expansion cohorts will enroll
      colorectal carcinoma patients. The IGM-8444 + birinapant combination expansion cohort will
      enroll solid tumor patients, IGM-8444 in combination with venetoclax will enroll patients
      with CLL/SLL.

      IGM-8444 will be administered intravenously (IV).

      An alternative dosing schedule may be evaluated.
    

Trial Arms

NameTypeDescriptionInterventions
IGM-8444 Single Agent EscalationExperimentalIGM-8444 will be administered intravenously as a single agent.
  • IGM-8444
IGM-8444 Single Agent Alternate Dosing EscalationExperimentalIGM-8444 will be administered intravenously as a single agent on an alternate dosing schedule.
  • IGM-8444
IGM-8444 + FOLFIRI EscalationExperimentalIGM-8444 will be administered intravenously in combination with FOLFIRI.
  • IGM-8444
  • FOLFIRI
IGM-8444 Single Agent ExpansionExperimentalIGM-8444 will be administered intravenously as a single agent in disease specific cohorts.
  • IGM-8444
IGM-8444 + FOLFIRI ExpansionExperimentalIGM-8444 will be administered intravenously in combination with FOLFIRI.
  • IGM-8444
  • FOLFIRI
IGM-8444 + FOLFIRI + Bevacizumab (and approved biosimilars) ExpansionExperimentalIGM-8444 will be administered intravenously in combination with FOLFIRI and bevacizumab (and approved biosimilars).
  • IGM-8444
  • FOLFIRI
  • Bevacizumab (and approved biosimilars)
IGM-8444 + Birinapant EscalationExperimentalIGM-8444 will be administered intravenously in combination with Birinapant which will also be administered intravenously.
  • IGM-8444
  • Birinapant
IGM-8444 + Birinapant ExpansionExperimentalIGM-8444 will be administered intravenously in combination with Birinapant which will also be administered intravenously.
  • IGM-8444
  • Birinapant
IGM-8444 + Venetoclax EscalationExperimentalIGM-8444 will be administered intravenously in combination with Venetoclax.
  • IGM-8444
  • Venetoclax
IGM-8444 + Venetoclax ExpansionExperimentalIGM-8444 will be administered intravenously in combination with Venetoclax.
  • IGM-8444
  • Venetoclax

Eligibility Criteria

        Key Inclusion Criteria:

          -  Age ≥ 18 years at time of signing Informed Consent Form

          -  Life expectancy of at least 12 weeks

          -  ECOG Performance Status of 0 or 1

          -  Patients who are either refractory to or intolerant of existing standard therapy or
             for whom no effective further standard of care therapy exists.

          -  No more than three prior therapeutic regimens ("therapeutic" is defined as any
             cytotoxic, biologic, or targeted therapy [approved or investigational] with intent to
             treat the cancer) administered for the treatment of cancer in the advanced/metastatic
             setting.

          -  For dose escalation cohorts only: Patients with either measurable or evaluable
             disease.

          -  Patients with histologic documentation of incurable, locally advanced or metastatic
             prostate cancer with non-measurable disease are eligible if they have an increase in
             prostate-specific antigen (PSA) level of > 50% from current level, the absolute
             increase is ≥ 5 ng/mL, and the increase is confirmed a second time.

          -  Patients with histologic documentation of incurable, locally advanced or metastatic
             ovarian cancer with non-measurable disease are eligible if they have an increase of >
             2 × the baseline level in CA-125 (or > 2 × the ULN in case of prior normal CA-125
             level) and the increase is confirmed a second time.

          -  Adequate organ function as evidenced by (hematologic parameters must be assessed at
             least 14 days from the last growth factor support or prior transfusion, if any):

               -  ANC ≥ 1000/μL.

               -  Total hemoglobin ≥ 9 g/dL.

               -  Platelet count ≥ 100,000/μL.

               -  Serum creatinine ≤ 1.5 × upper limit of normal (ULN), or estimated creatinine
                  clearance ≥ 50 mL/min (Cockcroft Gault or other institutional methods).

               -  Serum aspartate transaminase (AST) and serum ALT ≤ 2 × ULN.

                    -  AST and ALT ≤ 3 × ULN is allowed if liver function abnormalities are due to
                       underlying malignancy.

               -  Total serum bilirubin ≤ 1.5 × ULN regardless of liver involvement secondary to
                  tumor.

                    -  Inclusion of patients with increased serum indirect bilirubin (≤ 3 × ULN)
                       due to Gilbert's syndrome is permitted.

               -  Alkaline phosphatase ≤ 2.5 × the ULN

               -  Albumin ≥3.0 g/dL.

               -  No clinically significant pleural or peritoneal effusion requiring drainage.

        For birinapant combination cohorts only:

          -  ANC ≥ 1500/μL.

        For venetoclax combination cohorts only:

          -  Documented diagnosis of CLL that meets the International Workshop on Chronic
             Lymphocytic Leukemia (IWCLL) criteria

          -  Measurable nodal disease by computed tomography (CT) for SLL

          -  Relapsed/refractory disease with an indication for treatment

          -  Adequate marrow function independent of growth factor or transfusion support within 2
             weeks of screening as follows, unless cytopenia is due to marrow involvement of CLL
             Platelet counts ≥ 75,000/μL For those patients with a screening lymphocyte count <
             5,000 cells/μL, historical data confirming a lymphocyte count 5,000 cells/μL at time
             of diagnosis is required

        Key Exclusion Criteria:

          -  Prior DR5 agonist therapy.

          -  Prior Bcl-family inhibitor therapy

          -  Known clinically significant history of liver disease including Child-Pugh Class B or
             C, including active viral or other hepatitis (e.g., hepatitis B or hepatitis C virus),
             current alcohol abuse, non-alcoholic steatohepatitis (NASH), or cirrhosis.

          -  Diagnosis of any secondary malignancy within 3 years prior to enrollment

          -  Untreated or active central nervous system (CNS) metastases (progressing or requiring
             anticonvulsants or corticosteroids for symptomatic control).

          -  Current Grade > 1 toxicity (except alopecia and anorexia) from prior therapy. Patients
             with current Grade 2 chronic toxicities that are well-controlled by medications may be
             enrolled after discussion with medical monitor.

          -  For birinapant-containing combination cohort only:

               -  Patients who have previously received birinapant treatment

               -  History of allergic reactions attributed to compounds of similar chemical or
                  biologic composition to birinapant

          -  Known HIV positivity

          -  Requires concomitant chronic use of anti-tumor necrosis factor (anti-TNF) therapies
             (e.g. infliximab, golimumab, certolizumab, adalimumab, etanercept) within 5 half-lives
             of drug prior to Cycle 1 Day 1

          -  Requires systemic or chronic topical steroids or immunosuppressive therapy within 4
             weeks prior to study treatment or anticipated need of systemic corticosteroids or
             immunosuppressive therapy during study participation

          -  Evidence of active, non-infectious pneumonitis or history of clinically significant
             interstitial lung disease

          -  Chondrosarcoma Cohort: Mesenchymal, dedifferentiated, and extraskeletal myxoid
             chondrosarcoma subtypes

          -  For venetoclax-containing combination cohort only:

               -  Transformation of CLL to aggressive NHL (Richter's transformation or
                  pro-lymphocytic leukemia, or DLBCL or CNS involvement by CLL

               -  Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia

               -  History of confirmed progressive multifocal leukoencephalopathy (PML)

          -  Known HIV positivity

          -  Hypersensitivity to venetoclax or to any of the excipients

          -  Malabsorption syndrome or other condition that precludes enteral route of
             administration

          -  Inability to swallow a large number of tablets

          -  Treatment with any other anti-cancer agent, investigational or otherwise) within 4
             weeks or five half-lives of the drug, whichever is shorter, prior to first dose of
             study treatment

          -  Patients who have received the following agents:

               -  Strong and moderate CYP3A inhibitors (Appendix 12) within 7 days prior to the
                  first dose of study drug administration

               -  Strong and moderate CYP3A inducers (Appendix 12) within days prior to the first
                  dose of study drug administration

               -  Consumed grapefruit, grapefruit juice, Seville oranges (including marmalade
                  containing Seville oranges), Seville orange juice, or star fruit within 3 days
                  prior to the first dose of study drug and throughout venetoclax administration

          -  Vaccination with a live vaccine within 28 days prior to study treatment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse Events of IGM-8444 as a single agent as single agent and in combination with FOLFIRI +/- bevacizumab, IGM-8444 in combination with birinapant, and IGM-8444 in combination with venetoclax
Time Frame:From Cycle 1 Day 1 through 28 days after the final dose of study drug
Safety Issue:
Description:Incidence of treatment-related AEs graded according to the NCI Common Technology Criteria for Adverse Events (CTCAE) v5.0

Secondary Outcome Measures

Measure:Area Under the Curve (AUC) of IGM-8444
Time Frame:At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
Safety Issue:
Description:Area Under the Curve (AUC) of IGM-8444 as a single agent and in combination with FOLFIRI +/- bevacizumab, IGM-8444 in combination with birinapant, and IGM-8444 in combination with venetoclax
Measure:Clearance (CL) of IGM-8444
Time Frame:At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
Safety Issue:
Description:Clearance (CL) of IGM-8444 as a single agent and in combination with FOLFIRI +/- bevacizumab, IGM-8444 in combination with birinapant, and IGM-8444 in combination with venetoclax
Measure:Volume of distribution (V) of IGM-8444
Time Frame:At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
Safety Issue:
Description:Volume of distribution (V) of IGM-8444 as a single agent and in combination with FOLFIRI +/- bevacizumab, IGM-8444 in combination with birinapant, and IGM-8444 in combination with venetoclax
Measure:Immunogenicity
Time Frame:through end of treatment at approximately 6 months
Safety Issue:
Description:Immunogenicity as assessed by detection of anti-drug antibodies (ADAs) to IGM-8444
Measure:Objective Response Rate (ORR)
Time Frame:Study duration of approximately 36 months
Safety Issue:
Description:Preliminary efficacy of objective response rate (ORR)
Measure:Duration of Response (DoR)
Time Frame:Study duration of approximately 36 months
Safety Issue:
Description:Preliminary efficacy of duration of response (DoR)
Measure:Progression-Free Survival (PFS)
Time Frame:Study duration of approximately 36 months
Safety Issue:
Description:Preliminary efficacy of progression-free survival (PFS)

Details

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

Trial Keywords

  • Relapsed and/or Refractory
  • Metastatic Cancer
  • Advanced Tumors

Last Updated

August 20, 2021