The purpose of this Phase 1a/1b clinical trial is to test the safety of an investigational drug called IMGS-001 and to determine how well it can work in treating patients with advanced solid tumors that have come back or are not improving after receiving other drugs that are commonly used for their cancer. Phase 1a (Part 1) will test the safety of five different doses of IMGS-001 to use in further studies. Patients with cancer that have advanced or spread to other parts of the body following treatment with other available therapies will be treated in Part 1. Phase 1b (Part 2) will test two doses of IMGS-001 identified in Part 1 to further determine the safety and potential effectiveness in select cancer types.
Part 1 is a Phase 1a, first-in-human, open-label dose-escalation study to determine the safety, tolerability, and maximum tolerated dose (MTD) of IMGS-001. The safety, tolerability, PK parameters, and preliminary antitumor activity of IMGS-001 will be assessed in adult patients with advanced solid tumors refractory to appropriate standard of care (SOC) treatments. Based on the MTD and other information (e.g., tolerability, PK, PD, target engagement), multiple doses of IMGS-001 will be selected for further evaluation. Additional subjects may be backfilled across Phase 1a doses (or other intermediate doses at or below the MAD/MTD) to assure adequate clinical data to support dose optimization and selection of appropriate doses for use in the Phase 1b. Approximately 35 total subjects will be enrolled in Phase 1a. Part 2 is a Phase 1b, open-label, dose-expansion study of five prespecified tumor cohorts to assess preliminary antitumor activity of IMGS-001 in patients that are refractory or intolerant to other appropriate prior standard therapies. Stage 1 will consist of two separate cohort designs: 4 single-dose cohorts and 1 tumor specific dose optimization cohort in NSCLC. The 4 single dose Stage 1 cohorts will initially enroll approximately 10 subjects in each of the following cohorts treated with IMGS-001: * Cohort 1: Ovarian cancer (high-grade epithelial, fallopian tube, or primary peritoneal; PD-L1 positive \[CPS ≥1\]) * Cohort 2: 9p24.1 lymphomas (classic Hodgkin's, PMBCL) * Cohort 3: Nasopharyngeal cancer (non-keratinizing) * Cohort 4: Head and neck squamous cell carcinoma (HPV+, PD-L1 positive \[CPS ≥1\]) Each cohort will be assessed to meet efficacy criteria to continue into a randomized dose-optimization. Within each cohort that meets prespecified efficacy criteria, the expanded cohorts will have randomly assigned (1:1) subjects to receive one of two doses used in the Phase 1a. Within each Arm, 20 eligible subjects will be treated with the assigned dose of IMGS-001. For the Stage 1 dose optimization in the NSCLC cohort, approximately 20 subjects will initially be randomized 1:1 to one of two dose arms. If efficacy criteria are met, the cohort may be expanded to randomize approximately 20 additional subjects across these two doses.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
105
Every 2 weeks
Banner MD Anderson Cancer Center
Gilbert, Arizona, United States
RECRUITINGUC Irvine
Orange, California, United States
RECRUITINGSarcoma Oncology Center
Santa Monica, California, United States
RECRUITINGMoffitt Cancer Center
Tampa, Florida, United States
RECRUITINGSt. Elizabeth Healthcare
Edgewood, Kentucky, United States
RECRUITINGOchsner Clinic Foundation
New Orleans, Louisiana, United States
RECRUITINGWashU
St Louis, Missouri, United States
RECRUITINGFox Chase Cancer Center
Philadelphia, Pennsylvania, United States
RECRUITINGUPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, United States
RECRUITINGMD Anderson Cancer Center
Houston, Texas, United States
RECRUITING...and 3 more locations
Phase 1a- Safety and tolerability of IMGS-001 by dose-limiting toxicities and adverse events
Frequency and severity of dose limiting toxicities and adverse events
Time frame: 21 days
Phase 1b- Recommended Phase 2 dose (RP2D) of IMGS-001 for specified tumor-specific cohorts as a pharmacologically optimal dose (POD)
RP2D will be defined by pooling all available PK, PD, target engagement, efficacy, safety, and tolerability data from Part 1 and Part 2
Time frame: 12 months
Phase 1a- Maximum tolerable dose (MTD) of IMGS-001
Time frame: 12 months
Pharmacokinetics (PK) of IMGS-001 by terminal half life (t1/2)
Time frame: 12 months
Pharmacokinetics of IMGS-001 by Area Under the Curve (AUC)
Time frame: 12 months
Pharmacokinetics of IMGS-001 by Maximum Observed Concentration (Cmax)
Time frame: 12 months
Pharmacokinetics of IMGS-001 by Minimum Observed Concentration (Cmin)
Time frame: 12 months
Potential immunogenicity of IMGS-001 by measurement of positive anti-drug antibody (ADA) levels
Time frame: 12 months
Efficacy of IMGS-001 by Objective Response Rate (ORR) via RECIST 1.1 and iRECIST; Lugano Criteria (2014) will be used for the lymphoma arm.
Time frame: 12 months
Efficacy of IMGS-001 by Progression Free Survival (PFS)
Time frame: 12 months
Efficacy of IMGS-001 by Duration of Response (DOR)
Time frame: 12 months
Efficacy of IMGS-001 by Clinical Benefit Rate (CBR)
Time frame: 12 months
Phase 1b- Safety and tolerability of IMGS-001 by frequency and severity of Adverse Events
Time frame: 12 months
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