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
- Study HIC#:2000028780
- Last Updated:07/15/2021
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.
- Start Date03/05/2021
- End Date08/01/2023
Trial Purpose and 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.
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.