Clinical trial NCT05635643: Study of CHS-114 in Participants With Advanced Solid Tumors
Official title: A Phase 1 Study of CHS-114 in Participants With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Head and Neck Squamous Cell Carcinoma
Keywords: metastatic solid tumors
advanced solid tumors
Phase 1
SRF114
CCR8
safety
efficacy
immunotherapy
cancer
immuno-oncology
CHS-114
Lead sponsor: Coherus Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2022-12-02
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Key Inclusion Criteria - Arms 1a, 1b, 2, and 3

* 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.
* For Arms 1a, 1b, and 2 only, 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 liver metastases or documented Gilbert's syndrome).
* 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 × 10\^9/L, hemoglobin ≥ 8.0 g/dL, and platelet count ≥ 75 × 10\^9/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 women of childbearing potential 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.

Additional Inclusion Criteria - Arm 3 only

* Histologically or cytologically confirmed locally advanced or metastatic HNSCC (primary tumor location of oral cavity, oropharynx, hypopharynx, or larynx). Participants may not have a primary tumor site of nasopharynx (any histology).
* Participants should have been treated with anti-PD-1/PD-L1-directed systemic therapy for incurable recurrent, advanced, or metastatic disease and experienced progressive disease. targeting agent (separately or in combination therapy).
* Metastatic or locoregionally recurrent HNSCC malignancy that is incurable by surgery or radiotherapy.
* Consent to provide HPV status assessed by p16 and results from baseline PD-L1 IHC assay score.
* Consent to provide tumor tissue samples is required for enrollment.

Key Exclusion Criteria - Arms 1a, 1b, 2, and 3

* 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).

Additional Exclusion Criteria - Arm 3

• Received ≥ 2 prior systemic regimens for advanced/metastatic disease.

Primary outcomes:
measure: [Arms 1a, 1b, and 2] Rate of Dose Limiting Toxicity (DLT)
timeFrame: Assessed during first 21 days of treatment
measure: [Arm 2] Summary of adverse events (AEs) based on treatment emergent AEs (TEAEs), anti-drug antibodies (ADA), and laboratory values.
timeFrame: Up to 24 months
measure: [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.
timeFrame: Up to 24 months
Secondary outcomes:
measure: [Arms 1a and 1b] Summary of AEs based on TEAEs.
timeFrame: Up to 24 months
measure: [Arms 1a and 1b] ADAs to CHS-114
timeFrame: Up to 24 months
measure: [Arms 1a, 1b, 2, and 3] PK of CHS-114
timeFrame: Up to 24 months
measure: [Arms 1a, 1b, 2, and 3] Confirmed objective response rate (ORR)
timeFrame: Up to 24 months
measure: [Arms 1a, 1b, 2, and 3] Duration of response (DoR)
timeFrame: Up to 24 months
measure: [Arms 1a, 1b, 2, and 3] Disease control rate (DCR)
timeFrame: Up to 24 months
measure: [Arms 1a, 1b, 2, and 3] Progression-free survival (PFS)
timeFrame: Up to 24 months
measure: [Arms 1a, 1b, 2, and 3] Changes in FOXP3 levels in participants undergoing pretreatment and on-treatment tumor biopsies
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Oxnard
country: United States
facility: FOMAT Medical Research
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Center
state: California
city: Orlando
country: United States
facility: SCRI Lake Nona DDU (FL Cancer Specialists)
state: Florida
city: Atlanta
country: United States
facility: Emory Winship Cancer Institute
state: Georgia
city: Hinsdale
country: United States
facility: Hope & Healing Cancer Services
state: Illinois
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute - Karmanos Cancer Center
state: Michigan
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: San Antonio
country: United States
facility: START- San Antonio
state: Texas
city: West Valley City
country: United States
facility: START Mountain
state: Utah
city: Seattle
country: United States
facility: University of Washington/Fred Hutchinson Cancer Center
state: Washington
Study officials:
affiliation: Coherus BioSciences
name: Koho Izuka, MD
role: STUDY_DIRECTOR
References: