Study of SRF114 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a Phase 1/2, 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.

Detailed Description
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This is a Phase 1/2, open-label, first-in-human, dose-escalation and expansion study of SRF114, a monoclonal antibody that targets CCR8, as a monotherapy in patients with advanced solid tumors, that will be conducted in 2 parts: Part A: SRF114 monotherapy dose-escalation portion of the study will enroll approximately 30 patients with advanced solid tumors. Part B: SRF114 monotherapy expansion cohort(s) will evaluate the safety, efficacy, tolerability, pharmacokinetics, and pharmacodynamics of SRF114 in indication specific cohort(s). Up to approximately 40 patients will be enrolled.

Official Title
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A Phase 1/2 Study of SRF114 in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumor, Head and Neck Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: SRF114


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria - Parts A and B Patients must be ≥ 18 years of age. For Part A 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 30 days after the last dose of SRF114; 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 - Part B 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. Part B patients who agree to provide optional tumor biopsies 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 - Parts A and B 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 - Part B 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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A Monotherapy Dose Escalation<br>The Part A monotherapy dose escalation portion of the study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of SRF114 as monotherapy in up to 30 patients with advanced solid tumors, to determine the recommended phase 2 dose (RP2D) . | Drug: SRF114<br>* SRF114<br>|
| Experimental: Part B Monotherapy Expansion<br>The Part B monotherapy expansion will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of SRF114 monotherapy at the recommended phase 2 dose (RP2D) in up to 40 patients with Head and Neck Squamous Cell Carcinoma (HNSCC). | Drug: SRF114<br>* SRF114<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| [Part A] Rate of Dose Limiting Toxicity (DLT) | Evaluation of rate of DLT of SRF114 as a monotherapy. | Assessed during first 21 days of treatment | 
| [Part B] Confirmed objective response rate (ORR) | Confirmed objective response rate (ORR) based on RECIST v1.1 | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| [Part A, Part B] Summary of adverse events (AEs) based on treatment emergent AEs (TEAEs) | Safety and tolerability of SRF114 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 SRF114 | Serum will be collected and assessed for the development of ADAs to SRF114 | Up to 24 monthss | 
| [Part A, Part B] Pharmacokinetics (PK) of SRF114 | Serum concentrations of SRF114 will be collected and analyzed to evaluate the PK of SRF114 | Up to 24 months | 
| [Part A] Confirmed objective response rate (ORR) | Confirmed objective response rate (ORR) based on RECIST v1.1 | Up to 24 months | 
| [Part A, Part B] 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 | 
| [Part A, Part B] 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 | 
| [Part A, Part B] 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic solid tumors, advanced solid tumors, Phase 1, SRF114, CCR8, safety, efficacy, immunotherapy, cancer, immuno-oncology