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Study of CHS-114 in Participants With Advanced Solid Tumors

Phase 1
Recruiting
Conditions
Advanced Solid Tumor
Head and Neck Squamous Cell Carcinoma
Interventions
Registration Number
NCT05635643
Lead Sponsor
Coherus Biosciences, Inc.
Brief Summary

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.

Detailed Description

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
87
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 1a: CHS-114 Dose EscalationCHS-114Arm 1 monotherapy dose escalation portion of the study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of CHS-114 as monotherapy in up to 25 participants with advanced solid tumors, to determine the recommended dose for expansion (RDE).
Arm 1b: CHS-114 Dose ExpansionCHS-114Arm 1b monotherapy expansion will evaluate the safety, tolerability, PK, pharmacodynamics, and efficacy of CHS-114 monotherapy at 2 dose levels (potential recommended dose for expansion RDE in up to 5 participants in each dose level with Head and Neck Squamous Cell Carcinoma (HNSCC).
Arm 2: CHS-114 + toripalimab Dose EscalationCHS-114Arm 2 dose escalation will evaluate the safety, tolerability, PK, pharmacodynamics, and efficacy of CHS-114 in combination with toripalimab at 2 RDE levels in up to 6 participants in each dose level with HNSCC.
Arm 2: CHS-114 + toripalimab Dose EscalationtoripalimabArm 2 dose escalation will evaluate the safety, tolerability, PK, pharmacodynamics, and efficacy of CHS-114 in combination with toripalimab at 2 RDE levels in up to 6 participants in each dose level with HNSCC.
Arm 3: CHS-114 + toripalimab Dose ExpansionCHS-114Arm 3 dose expansion will evaluate the safety, tolerability, PK, pharmacodynamics, and efficacy of CHS-114 in combination with toripalimab at 2 RDE levels in up to 20 participants in each dose level with HNSCC.
Arm 3: CHS-114 + toripalimab Dose ExpansiontoripalimabArm 3 dose expansion will evaluate the safety, tolerability, PK, pharmacodynamics, and efficacy of CHS-114 in combination with toripalimab at 2 RDE levels in up to 20 participants in each dose level with HNSCC.
Primary Outcome Measures
NameTimeMethod
[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.Up to 24 months

Safety and tolerability of CHS-114 in combination with toripalimab

[Arms 1a, 1b, and 2] Rate of Dose Limiting Toxicity (DLT)Assessed during first 21 days of treatment

Evaluation of rate of DLT of CHS-114 as a monotherapy, or in combination with toripalimab

[Arm 2] Summary of adverse events (AEs) based on treatment emergent AEs (TEAEs), anti-drug antibodies (ADA), and laboratory values.Up to 24 months

Safety and tolerability of CHS-114 in combination with toripalimab,

Secondary Outcome Measures
NameTimeMethod
[Arms 1a, 1b, 2, and 3] Duration of response (DoR)Up to 24 months

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.

[Arms 1a, 1b, 2, and 3] Disease control rate (DCR)Up to 24 months

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.

[Arms 1a, 1b, 2, and 3] Progression-free survival (PFS)Up to 24 months

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.

[Arms 1a, 1b, 2, and 3] Changes in FOXP3 levels in participants undergoing pretreatment and on-treatment tumor biopsiesUp to 24 months

Cellular FOX3P expression within the tumor will be collected and analyzed in participants who are undergoing pretreatment and on-treatment biopsies

[Arms 1a and 1b] Summary of AEs based on TEAEs.Up to 24 months

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.

[Arms 1a and 1b] ADAs to CHS-114Up to 24 months

Serum will be collected and assessed for the development of ADAs to CHS-114

[Arms 1a, 1b, 2, and 3] PK of CHS-114Up to 24 months

Serum concentrations of CHS-114 will be collected and analyzed to evaluate the PK of CHS-114 and in Arms 2 and 3, toripalimab.

[Arms 1a, 1b, 2, and 3] Confirmed objective response rate (ORR)Up to 24 months

Confirmed objective response rate (ORR) based on RECIST v1.1

Trial Locations

Locations (14)

FOMAT Medical Research

🇺🇸

Oxnard, California, United States

Stanford Cancer Center

🇺🇸

Palo Alto, California, United States

SCRI Lake Nona DDU (FL Cancer Specialists)

🇺🇸

Orlando, Florida, United States

Emory Winship Cancer Institute

🇺🇸

Atlanta, Georgia, United States

Hope & Healing Cancer Services

🇺🇸

Hinsdale, Illinois, United States

University of Louisville

🇺🇸

Louisville, Kentucky, United States

University of Michigan

🇺🇸

Ann Arbor, Michigan, United States

Barbara Ann Karmanos Cancer Institute - Karmanos Cancer Center

🇺🇸

Detroit, Michigan, United States

Washington University

🇺🇸

Saint 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

START Mountain

🇺🇸

West Valley City, Utah, United States

University of Washington/Fred Hutchinson Cancer Center

🇺🇸

Seattle, Washington, United States

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