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.
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
Drug | Synonyms | Arms |
---|
IGM-8444 | | IGM-8444 + FOLFIRI + Bevacizumab Expansion |
FOLFIRI | Fluorouracil or 5-FU, Leucovorin, Irinotecan | IGM-8444 + FOLFIRI + Bevacizumab Expansion |
Bevacizumab | Avastin | IGM-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
Name | Type | Description | Interventions |
---|
IGM-8444 Single Agent Escalation | Experimental | IGM-8444 will be administered intravenously as a single agent. | |
IGM-8444 Single Agent Alternate Dosing Escalation | Experimental | IGM-8444 will be administered intravenously as a single agent on an alternate dosing schedule. | |
IGM-8444 + FOLFIRI Escalation | Experimental | IGM-8444 will be administered intravenously in combination with FOLFIRI. | |
IGM-8444 Single Agent Expansion | Experimental | IGM-8444 will be administered intravenously as a single agent in disease specific cohorts. | |
IGM-8444 + FOLFIRI Expansion | Experimental | IGM-8444 will be administered intravenously in combination with FOLFIRI. | |
IGM-8444 + FOLFIRI + Bevacizumab Expansion | Experimental | IGM-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