This is a Phase 1/2a open-label, multicenter, dose escalation and dose expansion trial in which IMT-009 will be administered by the intravenous (IV) route to participants with solid tumors or lymphomas. The main goals of this study are to: * Find the recommended dose of IMT-009 that can be safely given to participants * Learn more about the side effects of IMT-009 * Learn more about pharmacokinetics of IMT-009 * Learn more about the effectiveness of IMT-009 * Learn more about different pharmacokinetic biomarkers and how they might change in the presence of IMT-009
IMT-009 is an Fc-attenuated monoclonal antibody that binds with high affinity and selectivity to CD161, a receptor that is broadly expressed on NK and a subset of memory T cells, blocking interactions between the receptor and its cognate ligand, CLEC2D, which is expressed on the surface of both cancer cells and immune cells. Preclinical data confirm that CD161 blockade with IMT-009 results in enhanced anti-tumor activity. This is a Phase 1/2a, open label dose escalation study of IMT-009, a fully human monoclonal antibody targeting CD161, given as a single agent in Phase 1 and potentially in combination with other antineoplastic agents in Phase 2.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
67
Participants will receive an IV infusion of IMT-009 on Day 1 during each 21-day cycle.
Fruquintinib will be administered according to the FDA-approved United States Prescribing Information (USPI).
Site 9618
Tucson, Arizona, United States
Site 5000
Denver, Colorado, United States
Site 4100
Orlando, Florida, United States
Site 4060
Sarasota, Florida, United States
Site 4500
Oklahoma City, Oklahoma, United States
Site 9280
Portland, Oregon, United States
Site 3000
Nashville, Tennessee, United States
Site 9384
Austin, Texas, United States
Site 9112
Fairfax, Virginia, United States
Dose Escalation - number of participants with dose limiting toxicities (DLTs) from IMT-009 monotherapy
Time frame: 21 days (Cycle 1 Day 1- Cycle 1 Day 21)
Dose Escalation- Number of participants with adverse events following administration of IMT-009
Time frame: From informed consent (Cycle 0 Day -28) to 90 days after the last dose of IMT-009. Each cycle is 21 days
Phase 1b Cohort(s) number of participants with dose limiting toxicities (DLTs) from IMT-009 in combination with fruiquintinib
Time frame: 28 days (Cycle 1 Day 1- Cycle 1 Day 28)
Phase 1b Cohort(s) - Number of participants with adverse events following administration of IMT-009 in combination with fruiquintinib
Time frame: From informed consent (Cycle 0 Day -28) through 90 days after last dose of IMT-009. Each cycle is 28 days
Phase 2a Cohort(s) Overall Response Rate (ORR) based on RECIST 1.1 or Lugano criteria (lymphomas only) to assess anti-tumor activity of IMT-009 in each cohort
Time frame: Every 6 weeks from Cycle 1 Day 1, until disease progression or death or start of a new anti-cancer therapy, up to 2 years. Each cycle is 21 days.
Dose Escalation, PDE, Phase 1b and Phase 2a Cohort(s) - Pharmacokinetic Analysis: Area under the plasma concentration-time curve (AUC) of IMT-009 when given as monotherapy or in combination.
Time frame: Cycle 1 Day 1 to 90 days after treatment discontinuation, up to 2 years. Dose Escalation, PDE and Phase 2a cycles are 21 days. Phase 1b cycles are 28 days.
Dose Escalation, PDE, Phase 1b and Phase 2a Cohort(s) - Pharmacokinetic Analysis: Maximum plasma concentration (Cmax) of IMT-009 when given as monotherapy or in combination.
Time frame: Cycle 1 Day 1 to 90 days after treatment discontinuation, up to 2 years. Dose Escalation, PDE and Phase 2a cycles are 21 days. Phase 1b cycles are 28 days.
Dose Escalation, PDE, Phase 1b and Phase 2a Cohort(s) - Pharmacokinetic Analysis: Minimum plasma concentration (Cmin) of IMT-009 when given as monotherapy or in combination.
Time frame: Cycle 1 Day 1 to 90 days after treatment discontinuation, up to 2 years. Dose Escalation, PDE and Phase 2a cycles are 21 days. Phase 1b cycles are 28 days.
Dose Escalation, PDE, Phase 1b and Phase 2a Cohort(s) - Pharmacokinetic Analysis: Volume of distribution (Vd) of IMT-009 when given as monotherapy or in combination.
Time frame: Cycle 1 Day 1 to 90 days after treatment discontinuation, up to 2 years. Dose Escalation, PDE and Phase 2a cycles are 21 days. Phase 1b cycles are 28 days.
Dose Escalation, PDE, Phase 1b and Phase 2a Cohort(s) - Pharmacokinetic Analysis: Apparent volume of distribution at steady state determined after intravenous administration (Vss) of IMT-009 when given as monotherapy or in combination.
Time frame: Cycle 1 Day 1 to 90 days after treatment discontinuation, up to 2 years.Dose Escalation, PDE and Phase 2a cycles are 21 days. Phase 1b cycles are 28 days.
Dose Escalation, PDE, Phase 1b and Phase 2a Cohort(s) - Pharmacokinetic Analysis: Terminal half-life (t1/2) of IMT-009 when given as monotherapy or in combination.
Time frame: Cycle 1 Day 1 to 90 days after treatment discontinuation, up to 2 years. Dose Escalation, PDE and Phase 2a cycles are 21 days. Phase 1b cycles are 28 days.
Dose Escalation, PDE, Phase 1b and Phase 2a Cohort(s) - Pharmacokinetic Analysis: Time to maximum plasma concentration (Tmax) of IMT-009 when given as monotherapy or in combination
Time frame: Cycle 1 Day 1 to 90 days after treatment discontinuation, up to 2 years. Dose Escalation, PDE and Phase 2a cycles are 21 days. Phase 1b cycles are 28 days.
Dose Escalation, PDE, Phase 1b and Phase 2a Cohort(s) - Pharmacokinetic Analysis: Clearance of IMT-009 when given as monotherapy or in combination.
Clearance is the volume of plasma cleared of IMT-009 by the body per unit time.
Time frame: Cycle 1 Day 1 to 90 days after treatment discontinuation, up to 2 years. Dose Escalation, PDE and Phase 2a cycles are 21 days. Phase 1b cycles are 28 days.
Dose Escalation, PDE, Phase 1b and Phase 2a Cohort(s) - Number of participants who develop detectable anti-drug antibodies.
Time frame: Cycle 1 Day 1 to 90 days after treatment discontinuation, up to 2 years.Dose Escalation, PDE and Phase 2a cycles are 21 days. Phase 1b cycles are 28 days.
Dose Escalation, PDE and Phase 1b Cohort(s) - Receptor Occupancy (RO) to determine the target engagement of IMT-009.
Time frame: Cycle 1 Day 1 to treatment discontinuation, up to 2 years. Dose Escalation and PDE cycles are 21 days. Phase 1b cycles are 28 days.
Dose Escalation, PDE and Phase 1b Cohort(s) - Overall Response Rate (ORR) based on RECIST 1.1 or Lugano criteria (lymphomas only) to assess anti-tumor activity of IMT-009.
Time frame: Every 6 weeks from Cycle 1 Day 1, until disease progression or death or start of a new anti-cancer therapy, up to 2 years. Dose Escalation and PDE cycles are 21 days. Phase 1b cycles are 28 days.
Dose Escalation, PDE, Phase 1b and Phase 2a Cohort(s) - Clinical benefit rate (CBR) based on RECIST 1.1 or Lugano criteria (lymphomas only) to assess preliminary anti-tumor activity of IMT-009.
Time frame: Every 6 weeks from Cycle 1 Day 1, until disease progression or death or start of a new anti-cancer therapy, up to 2 years. Dose Escalation, PDE and Phase 2a cycles are 21 days. Phase 1b cycles are 28 days.
Dose Escalation, PDE, Phase 1b and Phase 2a Cohort(s) - Duration of Response (DOR) based on RECIST 1.1 or Lugano criteria (lymphomas only) to assess preliminary anti-tumor activity of IMT-009.
Time frame: Every 6 weeks from Cycle 1 Day 1, until disease progression or death or start of a new anti-cancer therapy, up to 2 years. Dose Escalation, PDE and Phase 2a cycles are 21 days. Phase 1b cycles are 28 days.
Dose Escalation, PDE, Phase 1b and Phase 2a Cohort(s) - Progression-free survival (PFS) based on RECIST 1.1 or Lugano criteria (lymphomas only) to assess preliminary anti-tumor activity of IMT-009.
Time frame: Every 6 weeks from Cycle 1 Day 1, until disease progression or death or start of a new anti-cancer therapy, up to 2 years. Dose Escalation, PDE and Phase 2a cycles are 21 days. Phase 1b cycles are 28 days.
Dose Escalation, PDE, Phase 1b and Phase 2a Cohort(s) - Overall survival (OS) to assess preliminary anti-tumor activity of IMT-009.
Time frame: Cycle 1 Day to discontinuation of study drug, then every 3 months for up to 2 years.
Phase 2a Cohort(s)- Number of participants with adverse events following administration of IMT-009.
Time frame: From informed consent (Cycle 0 Day -28) to 30 days after the last dose of IMT-009. Each cycle is 21 days.
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