This is a Phase 1, open-label, first-in-human, dose-escalation and expansion study of CHS-114, a monoclonal antibody that targets CCR8, as a monotherapy in patients with solid tumors.
This is a Phase 1, open-label, first-in-human, dose-escalation and expansion study of CHS-114, a monoclonal antibody that targets CCR8, as a monotherapy in participants with advanced solid tumors, that will be conducted in 3 parts: * Arm 1a: CHS-114 monotherapy dose-escalation portion of the study will enroll approximately 25 participants with advanced solid tumors. * Arm 1b: CHS-114 monotherapy expansion cohort(s) will evaluate the safety, efficacy, tolerability, pharmacokinetics, and pharmacodynamics of CHS-114 in indication specific cohort(s). Up to approximately 10 participants will be enrolled. * Arm 2: CHS-114 + toripalimab combination dose-escalation portion of the study will evaluate the safety, efficacy, tolerability, pharmacokinetics, and pharmacodynamics of CHS-114 in combination with toripalimab in indication specific cohort(s). Up to approximately 6-12 participants will be enrolled. * Arm 3: CHS-114 + toripalimab combination dose-expansion portion of the study will evaluate the safety, efficacy, tolerability, pharmacokinetics, and pharmacodynamics of CHS-114 in combination with toripalimab in indication specific cohort(s). Up to approximately 40 participants will be randomized to two dosing arms.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
87
CHS-114
toripalimab-tpzi
Stanford Cancer Center
Palo Alto, California, United States
Emory Winship Cancer Institute
Atlanta, Georgia, United States
University of Louisville
Louisville, Kentucky, United States
[Arms 1a, 1b, and 2] Rate of Dose Limiting Toxicity (DLT)
Evaluation of rate of DLT of CHS-114 as a monotherapy, or in combination with toripalimab
Time frame: Assessed during first 21 days of treatment
[Arm 2] Summary of adverse events (AEs) based on treatment emergent AEs (TEAEs), anti-drug antibodies (ADA), and laboratory values.
Safety and tolerability of CHS-114 in combination with toripalimab,
Time frame: Up to 24 months
[Arm 3] Safety and tolerability of CHS-114 in combination with toripalimab will be assessed by summarizing AEs and will be based on TEAEs as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 or higher.
Safety and tolerability of CHS-114 in combination with toripalimab
Time frame: Up to 24 months
[Arms 1a and 1b] Summary of AEs based on TEAEs.
Safety and tolerability of CHS-114 as monotherapy will be assessed by summarizing AEs and will be based on TEAEs as assessed by CTCAE v5.0 or higher.
Time frame: Up to 24 months
[Arms 1a and 1b] ADAs to CHS-114
Serum will be collected and assessed for the development of ADAs to CHS-114
Time frame: Up to 24 months
[Arms 1a, 1b, 2, and 3] PK of CHS-114
Serum concentrations of CHS-114 will be collected and analyzed to evaluate the PK of CHS-114 and in Arms 2 and 3, toripalimab.
Time frame: Up to 24 months
[Arms 1a, 1b, 2, and 3] Confirmed objective response rate (ORR)
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University of Maryland Greenebaum Comprehensive Cancer Center
Baltimore, Maryland, United States
University of Michigan
Ann Arbor, Michigan, United States
Barbara Ann Karmanos Cancer Institute - Karmanos Cancer Center
Detroit, Michigan, United States
Washington University
St Louis, Missouri, United States
University of Cincinnati
Cincinnati, Ohio, United States
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States
START- San Antonio
San Antonio, Texas, United States
...and 2 more locations
Confirmed objective response rate (ORR) based on RECIST v1.1
Time frame: Up to 24 months
[Arms 1a, 1b, 2, and 3] Duration of response (DoR)
Duration of response (DoR) based on RECIST v1.1. DoR is defined as the time from the first documented response (CR or PR) to documented disease progression as determined by RECIST v1.1 or death.
Time frame: Up to 24 months
[Arms 1a, 1b, 2, and 3] Disease control rate (DCR)
DCR based on RECIST v1.1. DCR is defined as the percentage of patients with CR, partial PR, or stable disease lasting a minimum of 12 weeks.
Time frame: Up to 24 months
[Arms 1a, 1b, 2, and 3] Progression-free survival (PFS)
PFS based on RECIST v1.1. PFS is defined as the time from the first treatment on study with study drug to documented disease progression as determined by RECIST v1.1 or death.
Time frame: Up to 24 months
[Arms 1a, 1b, 2, and 3] Changes in FOXP3 levels in participants undergoing pretreatment and on-treatment tumor biopsies
Cellular FOX3P expression within the tumor will be collected and analyzed in participants who are undergoing pretreatment and on-treatment biopsies
Time frame: Up to 24 months