Study of CHS-114 in Participants With Advanced Solid Tumors

Coherus BioSciences

Status and phase: Enrolling; Phase 1

Conditions: Advanced Solid Tumor; Head and Neck Squamous Cell Carcinoma

Treatments: Drug: CHS-114; Drug: toripalimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05635643

SRF114-101

Details and patient eligibility

About

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.

Full 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.

Enrollment: 87 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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87 participants in 4 patient groups

Arm 1a: CHS-114 Dose Escalation

Experimental group

Description:

Arm 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).

Treatment:

Drug: CHS-114

Arm 1b: CHS-114 Dose Expansion

Experimental group

Description:

Arm 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).

Treatment:

Drug: CHS-114

Arm 2: CHS-114 + toripalimab Dose Escalation

Experimental group

Description:

Arm 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.

Treatment:

Drug: toripalimab

Drug: CHS-114

Arm 3: CHS-114 + toripalimab Dose Expansion

Experimental group

Description:

Arm 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.

Treatment:

Drug: toripalimab

Drug: CHS-114