Study of SRF114 in Patients With Advanced Solid Tumors
Study of SRF114 in Patients With Advanced Solid Tumors
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.
SRF114, a monoclonal antibody that targets CCR8, as a monotherapy in patients with solid
tumors.
Not Available
Phase I
Adults
Not Available
Not Available
Choe, Jennifer
National
Vanderbilt University
12-17-2024
Eligibility
18 Years
BOTH
YES
Inclusion Criteria:
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).
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).
