Study of IGM-8444 as a Single Agent and in Combination With Chemotherapy-based Regimens in Subjects With Solid Cancers

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

Sponsors

Lead Sponsor: IGM Biosciences, Inc.

Source IGM Biosciences, Inc.
Brief Summary

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.

Overall Status Recruiting
Start Date September 23, 2020
Completion Date October 2023
Primary Completion Date August 2023
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Adverse Events of IGM-8444 as a single agent as single agent and in combination with FOLFIRI +/- bevacizumab. 8 weeks
Recommended Phase 2 Dose (RP2D) of IGM-8444 as a single agent as single agent and in combination with FOLFIRI +/- bevacizumab. 4 weeks
Secondary Outcome
Measure Time Frame
Area Under the Curve (AUC) of IGM-8444 At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
Clearance (CL) of IGM-8444 At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
Volume of distribution (V) of IGM-8444 At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
Immunogenicity through end of treatment at approximately 6 months
Objective Response Rate (ORR) Study duration of approximately 36 months
Duration of Response (DoR) Study duration of approximately 36 months
Progression-Free Survival (PFS) Study duration of approximately 36 months
Enrollment 230
Condition
Intervention

Intervention Type: Drug

Intervention Name: IGM-8444

Description: DR5 Agonist Investigational Drug

Intervention Type: Drug

Intervention Name: FOLFIRI

Description: Chemotherapy Regimen

Intervention Type: Drug

Intervention Name: Bevacizumab

Description: Targeted Therapy

Arm Group Label: IGM-8444 + FOLFIRI + Bevacizumab Expansion

Other Name: Avastin

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Eric Humke, MD, PhD Study Director IGM Biosciences
Overall Contact

Last Name: Clinical Trials

Phone: 650 265 6428

Email: [email protected]

Location
Facility: Status: Contact:
Florida Cancer Specialists | Sarasota, Florida, 34232, United States Recruiting Clinical Trials [email protected]
SCRI - Tennessee | Nashville, Tennessee, 37203, United States Recruiting Clinical Trials [email protected]
Location Countries

United States

Verification Date

October 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 6
Arm Group

Label: IGM-8444 Single Agent Escalation

Type: Experimental

Description: IGM-8444 will be administered intravenously as a single agent.

Label: IGM-8444 Single Agent Alternate Dosing Escalation

Type: Experimental

Description: IGM-8444 will be administered intravenously as a single agent on an alternate dosing schedule.

Label: IGM-8444 + FOLFIRI Escalation

Type: Experimental

Description: IGM-8444 will be administered intravenously in combination with FOLFIRI.

Label: IGM-8444 Single Agent Expansion

Type: Experimental

Description: IGM-8444 will be administered intravenously as a single agent in disease specific cohorts.

Label: IGM-8444 + FOLFIRI Expansion

Type: Experimental

Description: IGM-8444 will be administered intravenously in combination with FOLFIRI.

Label: IGM-8444 + FOLFIRI + Bevacizumab Expansion

Type: Experimental

Description: IGM-8444 will be administered intravenously in combination with FOLFIRI with bevacizumab.

Study Design Info

Allocation: Non-Randomized

Intervention Model: Sequential Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov