Clinical Trials /

Study of IGM-8444 as a Single Agent and in Combination With Chemotherapy-based Regimens in Subjects With 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 with a chemotherapy-based regimen in patients with relapsed and/or refractory solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of IGM-8444 as a Single Agent and in Combination With Chemotherapy-based Regimens in Subjects With Solid Cancers
  • Official Title: An Open-label, Multicenter, Phase I Study of IGM-8444 as a Single Agent and in Combination With Chemotherapy-based Regimens 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's Lymphoma
  • Non-Small Cell Lung Cancer
  • Sarcoma

Interventions

DrugSynonymsArms
IGM-8444IGM-8444 + FOLFIRI + Bevacizumab Expansion
FOLFIRIFluorouracil or 5-FU, Leucovorin, IrinotecanIGM-8444 + FOLFIRI + Bevacizumab Expansion
BevacizumabAvastinIGM-8444 + FOLFIRI + Bevacizumab Expansion

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 with a chemotherapy-based regimen in patients with relapsed and/or refractory solid tumors.

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 and
      IGM-8444 in combination with FOLFIRI for colorectal carcinoma patients. The IGM-8444 single
      agent expansion cohort will enroll the following tumor types: colorectal carcinoma, gastric,
      non-small cell lung cancer, sarcoma, and an all-comers cohort which will include
      relapsed/refractory non-hodgkins lymphoma patients. The IGM-8444 + FOLFIRI with or without
      bevacizumab combination expansion cohorts will enroll colorectal carcinoma patients. 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 ExpansionExperimentalIGM-8444 will be administered intravenously in combination with FOLFIRI with bevacizumab.
  • IGM-8444
  • FOLFIRI
  • Bevacizumab

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.

        Key Exclusion Criteria:

          -  Prior DR5 agonist therapy.

          -  Prior Bcl-family inhibitor therapy

          -  Concomitant use of agents well-known to cause liver toxicity.

          -  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.
      
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.
Time Frame:8 weeks
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
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
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
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 Colorectal Carcinoma
  • Advanced Tumor

Last Updated

September 11, 2020