Solid Tumor
Conditions
Keywords
Relapsed and/or Refractory, Metastatic Cancer, Advanced Tumors, Incurable
Brief summary
This study is a first-in-human (FIH), Phase 1, multicenter, open-label study to evaluate the safety, tolerability, and PK of IGM-7354 in participants with relapsed and/or refractory tumors. The study design consists of a dose-escalation stage and dose-expansion stage. Study participation will consist of a 28-day screening period, a treatment period, and a safety follow-up period 90-days after the last dose.
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-7354 safety and tolerability in patients with relapsed and/or refractory solid tumors. The dose expansion serial biopsy cohort will assess the intra-tumoral PD changes related to the activity of IGM-7354. IGM-7354 will be administered intravenously (IV).
Interventions
DRUGIGM-7354
IGM-7354 is a PD-L1-targeted cytokine that is designed to regulate T and natural killer cell activation, proliferation and promote their anti-tumor effects
Sponsors
IGM Biosciences, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Age \> 18 years at time of signing ICF * ECOG Performance Status of 0 or 1 * Histologic or cytologic documentation of incurable, locally advanced or metastatic solid tumors for which standard therapies are not available, are no longer effective, are not tolerated, or have been declined by the participant * Participants with either measurable or evaluable disease * Adequate organ function * At least 2 weeks prior to Day 1 or 5 half-lives, whichever is shorter, must have elapsed from the use of anti-tumor therapy, including chemotherapy, biologic, experimental, or hormonal therapy * Participants must be willing to have pre-treatment and on-treatment tumor biopsies for biomarker evaluation Key
Exclusion criteria
* Inability to comply with study and follow-up procedures * Prior IL-15, IL-2, synthetic IL-2, or IL-2v based therapy * History of severe allergic or anaphylactic reactions to monoclonal antibody therapy * Palliative radiation to bone metastases within 2 weeks prior to Day 1 * Major surgical procedure within 4 weeks prior to Day 1 * Untreated or active central nervous system (CNS) metastases. Patients with a history of treated CNS metastases are eligible. * Active autoimmune disease that has required systemic treatment in the past 2 years. * Diagnosis of immunodeficiency * Current Grade \>1 toxicity from prior therapy. Participants with current Grade 2 chronic toxicities that are well-controlled by medications may be enrolled after discussion with medical monitor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the safety and tolerability of IGM-7354 in participants with cancer including estimation of the MTD or MAD | At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 12 months (each cycle is 28 days) | Incidence of treatment-emergent AEs, SAEs, and DLT per NCI CTCAE v5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clearance (CL) of IGM-7354 | At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 12 months (each cycle is 28 days) | Clearance (CL) of IGM-7354 as a single agent |
| Volume of distribution (V) of IGM-7354 | At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 12 months (each cycle is 28 days) | Volume of distribution (V) of IGM-7354 as a single agent |
| Maximum Plasma Concentration (Cmax) of IGM-7354 | At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 12 months (each cycle is 28 days) | Maximum Plasma Concentration (Cmax) of IGM-7354 as a single agent |
| Area Under the Curve (AUC) of IGM-7354 | At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 12 months (each cycle is 28 days) | Area Under the Curve (AUC) of IGM-7354 as a single agent |
| Duration of Response (DoR) | Study duration of approximately 29 months | For participants who demonstrate confirmed CR or PR, duration of response is defined as the time from the first documented CR or PR to the first documented disease progression or death, whichever occurs first. |
| Progression-Free Survival (PFS) | Study duration of approximately 29 months | PFS is defined as the time from first dose to the first documented disease progression per RECIST 1.1 by investigator or death, whichever occurs first. |
| Anti-drug antibodies (ADAs) of IGM-7354 | At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 12 months (each cycle is 28 days) | Immunogenicity of IGM-7354 |
| Objective Response Rate (ORR) | Study duration of approximately 29 months | The ORR is defined as the percentage of participants who achieve a confirmed complete response (CR) or partial response (PR) per RECIST 1.1 as assessed by investigators |
Countries
United States
Outcome results
None listed