Study of CHS-114 in Participants With Advanced Solid Tumors

A Phase 1 Study of CHS-114 in Participants With Advanced Solid Tumors

This is a Phase 1, open-label, first-in-human, dose-escalation and expansion study of SRF114, a monoclonal antibody that targets CCR8, as a monotherapy in patients with solid tumors.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor; Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: CHS-114; Drug: toripaliamab

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.

• Study Type: Interventional
• Enrollment (Estimated): 47
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Hillary O'Kelly; Phone Number: 805551-1699; Email: hokelly@coherus.com

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University
      • Contact: Samuel Williams; Phone Number: 314-747-2626; Email: wsamuel@wustl.edu
      • Contact: Douglas Adkins, MD; Phone Number: 314.747.2626; Email: dadkins@wustl.edu
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • START- San Antonio
      • Contact: Amita Patnaik
  • Utah
    • West Valley City, Utah, United States, 84119
      • Recruiting
      • START Mountain
      • Contact: Marianne Herden; Phone Number: 801-907-4753; Email: marianne.herndon@startthecure.com
      • Contact: Justin Call, MD; Phone Number: 801-907-4753; Email: justin.call@startthecure.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria - Arms 1a, 1b, and 2

• Participants must be ≥ 18 years of age.
• For Arm 1a only, locally advanced or metastatic (Stage IV) solid tumor that has progressed during or after standard therapy and for whom no available therapies are appropriate (based on the judgment of the Investigator).
• At least 1 measurable lesion per RECIST 1.1.
• Lesions previously treated with radiation or other forms of locoregional therapy must show radiographic evidence of disease progression to be used as a target lesion.
• Washout period from the last dose of previous anticancer therapy (chemotherapy, biologic, or other investigational agent) to the initiation of study drug must be > 5 times the half-life of the agent or > 21 days (whichever is shorter).
• Resolution of non-immune-related AEs secondary to prior anticancer therapy (excluding alopecia and peripheral neuropathy) to ≤ Grade 1 per NCI-CTCAE version 5.0 or higher, and complete resolution of immune-related AEs secondary to prior checkpoint inhibitor therapy.
• Serum creatinine clearance ≥ 30 mL/min per Cockcroft-Gault formula.
• Total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN if elevated because of Gilbert's syndrome and ≤ 2 × ULN for patients with hepatocellular carcinoma [HCC] or patients with known liver metastases).
• Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) < 2.5 × ULN or < 5 × ULN for patients with known liver metastases.
• Adequate hematologic function, defined as absolute neutrophil count ≥ 1.0 × 109/L, hemoglobin ≥ 9.0 g/dL, and platelet count ≥ 75 × 109/L.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Ejection fraction ≥ 50%, as measured by echocardiogram, multigated acquisition scan, nuclear stress test, or equivalent modality.
• Willingness of male and female patients who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control for the duration of the study treatment period, including 90 days after the last dose of CHS-114, 4 months after the last dose of toripalimab; male patients must refrain from donating sperm during this period. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception. Azoospermic male patients and WCBP who are continuously not heterosexually active are exempt from contraceptive requirements.

Additional Inclusion Criteria - Arms 1b and 2 only

• Histologically or cytologically confirmed advanced or metastatic HNSCC that has progressed during or after a platinum-based chemotherapy and/or a programmed cell death receptor (PD)-1 or PD ligand 1 (PD-L1) targeting agent (separately or in combination therapy).
• Metastatic or locoregionally recurrent HNSCC malignancy that is incurable by surgery or radiotherapy.
• Arm 1b only, participants must have tumor tissue that is accessible for pretreatment and on-treatment tumor biopsy in the opinion of the Investigator and be willing and consent to undergo pretreatment and on-treatment biopsies per protocol.

Key Exclusion Criteria - Arms 1a, 1b, and 2

• Previously received an anti-CCR8 antibody or anti-CCR8 targeted therapy.
• History of Grade 4 allergic or anaphylactic reaction to any monoclonal antibody therapy or any excipient in the study drugs.
• Major surgery within 4 weeks prior to Screening.
• Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition including pneumonitis and/or interstitial lung disease, uncontrolled diabetes, symptomatic fistula) or any important medical illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the risk to the patient associated with his or her participation in the study.

Additional Exclusion Criteria - Arms 1b and 2 only

• Received > 4 prior systemic regimens for advanced/metastatic disease.
• Nasopharyngeal carcinoma or nasal cavity malignancies other than HNSCC (eg, adenocarcinoma and variants, neuroendocrine tumors, mucosal melanoma).
• Receiving chronic anti-coagulation therapy (eg, warfarin, enoxaparin) that cannot be safely discontinued temporarily for the required biopsies (only for patients who provide tumor biopsies).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1a: CHS-114 Dose Escalation; Arm 1 monotherapy dose escalation portion of the study will evaluate the safety, tolerability, pharmacokinetics, 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).	Drug: CHS-114; CHS-114
Experimental: Arm 1b: CHS-114 Dose Expansion; Arm 1b monotherapy expansion will evaluate the safety, tolerability, pharmacokinetics, 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).	Drug: CHS-114; CHS-114
Experimental: Arm 2: CHS-114 + toripalimab Dose Expansion; Arm 2 combination dose expansion will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of CHS-114 in combination with toripalimab at 2 dose recommended Phase 2 dose [RDE] levels in up to 6 participants in each dose level with Head and Neck Squamous Cell Carcinoma (HNSCC).	Drug: CHS-114; CHS-114; Drug: toripaliamab; toripalimab-tpzi; Other Names: Loqtorzi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[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	Assessed during first 21 days of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[Arms 1a and 1b] Summary of adverse events (AEs) based on treatment emergent AEs (TEAEs).	Safety and tolerability of CHS-114 as monotherapy, and in combination with toripalimab, will be assessed by summarizing adverse events (AEs) and will be based on treatment-emergent adverse events (TEAEs) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 or higher.	Up to 24 months
Anti-drug Antibodies (ADAs) to CHS-114	Serum will be collected and assessed for the development of ADAs to CHS-114	Up to 24 months
[Arms 1a, 1b, and 2] Pharmacokinetics (PK) of CHS-114	Serum concentrations of CHS-114 will be collected and analyzed to evaluate the PK of CHS-114 and in Arm 2 toripalimab.	Up to 24 months
[Arms 1a, 1b, and 2] Confirmed objective response rate (ORR)	Confirmed objective response rate (ORR) based on RECIST v1.1	Up to 24 months
[Arms 1a, 1b, and 2] 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.	Up to 24 months
[Arms 1a, 1b, and 2] Disease control rate (DCR)	Disease control rate (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.	Up to 24 months
[Arms 1a, 1b, and 2] Progression-free survival (PFS)	Progression-free survival (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.	Up to 24 months
[Arms 1a and 1b] 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	Up to 24 months

Collaborators and Investigators

• Sponsor: Coherus Biosciences, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2022
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: November 14, 2022
• First Submitted That Met QC Criteria: November 22, 2022
• First Posted (Actual): December 2, 2022

Study Record Updates

• Last Update Posted (Actual): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: safety; immunotherapy; cancer; Phase 1; efficacy; advanced solid tumors; metastatic solid tumors; immuno-oncology; SRF114; CCR8; CHS-114
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: SRF114-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No