Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCSF
Dates
study started
estimated completion
Principal Investigator
by Kate Kelley (ucsf)

Description

Summary

This is a Phase 1/1b, open-label, first-in-human, dose-escalation and expansion study of SRF388, a monoclonal antibody that targets IL-27, as a monotherapy and in combination in patients with solid tumors.

Official Title

A Phase 1/1b Study of SRF388 in Patients With Advanced Solid Tumors

Details

This is a Phase 1/1b, open-label, first-in-human (FIH), dose-escalation and expansion study of SRF388, a monoclonal antibody targeting IL-27, as a monotherapy and in combination in patients with solid tumors that will be conducted in 3 parts: - Part A: SRF388 monotherapy dose-escalation portion of the study will evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary efficacy of SRF388 as monotherapy in patients with advanced solid tumors. - Part B: SRF388 monotherapy expansion cohorts will evaluate the safety, efficacy, tolerability, PK, and pharmacodynamics of SRF388 monotherapy in patients with advanced or metastatic ccRCC (any clear cell component in the histologic definition) and advanced or metastatic HCC in indication specific cohorts. - Part C will evaluate the safety, preliminary efficacy, tolerability, and PK of SRF388 in combination with pembrolizumab in patients with advanced RCC or HCC.

Keywords

Advanced Solid Tumor Clear Cell Renal Cell Carcinoma Hepatocellular Carcinoma metastatic solid tumors advanced solid tumors Phase 1 SRF388 IL-27 safety efficacy immunotherapy cancer immuno-oncology kidney cancer renal cell carcinoma liver cancer Carcinoma Neoplasms Carcinoma, Hepatocellular Carcinoma, Renal Cell Pembrolizumab

Eligibility

For people ages 18 years and up

Part A and Part B Abbreviated Inclusion Criteria:

  • ≥ 18 years of age
  • 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 investigator judgment)
  • Patients in Part B with advance or metastatic ccRCC or HCC must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Patients with HCC in Part B must have at least 1 measurable target lesion according to modified RECIST (mRECIST)
  • Patients with HCC must have unresectable disease, Barcelona Clinic Liver Cancer (BCLC1) Stage B (not eligible for transcatheter arterial chemoembolization [TACE]) or Stage C
  • For patients in Part B with ccRCC, demonstrated progressive disease (PD) during or after the most recent treatment regimen. Prior treatment history must include progression during or after treatment with regimen(s) that have included a vascular endothelial growth growth factor (VEGF)-targeted agent and an immune checkpoint inhibitor. Patients who did not progress on but discontinued the VEGF-targeted agent for toxicity or intolerability are permitted.
  • For patients in Part B with HCC, demonstrated PD during or after the most recent treatment regimen. Prior treatment history must include progression during or after treatment with a VEGF-targeted agent. Patients who did not progress on but discontinued the VEGF-targeted agent for toxicity or intolerability are permitted.
  • For Part B patients in the tumor biopsy subsets only, must have tumor tissue that is accessible for pretreatment and on-treatment tumor biopsy in the opinion of the Investigator and be willing to undergo pretreatment and on-treatment biopsies per protocol
  • Serum creatinine clearance ≥ 30 mL/min per Cockcroft-Gault formula or serum creatinine ≤ 2.0 x the upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 x ULN (≤ 3 x ULN if elevated because of Gilbert's syndrome and ≤ 2 x ULN for patients with HCC or patients with known liver metastases)
  • Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) < 2.5 x ULN (< 5 x ULN if liver metastasis or for patients with HCC)
  • For patients with HCC, Child-Pugh class A or B7 with a serum albumin ≥ 2.8 g/dL (≥ 28 g/L)
  • Adequate hematologic function, defined as absolute neutrophil count (ANC) ≥ 1.0 x 109/L, hemoglobin ≥ 9.0 g/dL, and platelet count ≥ 100 x 109/L. For patients with HCC, platelet count ≥ 75 x 109/L without transfusion
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1

Part C Abbreviated Inclusion Criteria:

  • Advanced RCC of any histology or advanced HCC previously treated with at least one systemic anticancer therapy
  • Patients with HCC must have unresectable disease, Barcelona Clinic Liver Cancer (BCLC) Stage B (not eligible for transcatheter arterial chemoembolization) or Stage C
  • At least 1 measurable lesion per RECIST 1.1
  • Patients with HCC must have at least 1 measurable target lesion according to modified RECIST (mRECIST)
  • ANC ≥1000/µL (1.0 x 109/L)
  • Platelets ≥100 000/µL (≥ 100 x 109/L)
  • Hemoglobin for participants with RCC: ≥9.0 g/dL1; for participants with HCC: ≥8.5 g/dL1
  • Creatinine OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN
  • Total bilirubin ≤1.5 × ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN
  • AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
  • International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
  • For patients with HCC, Child-Pugh class A or B7 with a serum albumin ≥ 2.8 g/dL (≥ 28 g/L)
  • 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 drug period (or beginning 14 days before the initiation of pembrolizumab for oral contraception), including 75 days after the last dose of SRF388 or 120 days after the last dose of pembrolizumab; male patients must refrain from donating sperm during this period. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception with spermicide. Azoospermic male patients and WCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, female patients must still undergo pregnancy testing as described in this section.

Part C Abbreviated Inclusion Criteria Specific to Patients with RCC or HCC from Part A or

Part B:

  • Progressed on SRF388 by RECIST 1.1
  • Did not experience prior Grade ≥ 3 toxicity related to SRF388
  • Willingness to undergo pretreatment core or excisional biopsy if deemed safe and tumor is accessible, in the opinion of the Investigator
  • Has received no systemic anticancer therapies between SRF388 doses

Part A and Part B Abbreviated Exclusion Criteria:

  • Previously received an anti-IL-27 antibody or anti-IL-27 targeted therapy
  • For patients in Part B with renal cell carcinoma (RCC), non-clear cell RCC histology
  • For patients with HCC, fibrolamellar or mixed hepatocellular cholangiocarcinoma
  • 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) 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

Part C Abbreviated Exclusion Criteria:

  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study drug
  • Previously received an anti-IL 27 antibody or anti-IL 27 targeted therapy (exception to patients who received SRF388 in Part A or Part B)
  • No prior systemic therapy for unresectable or metastatic disease
  • Received > 5 prior systemic regimens for unresectible or metastatic disease (prior PD-(L)1 inhibitors are allowed if the patient did not discontinue therapy due to ≥ Grade 3 drug-related toxicity)
  • For patients with HCC, fibrolamellar histology or mixed hepatocellular cholangiocarcinoma
  • For patients with HCC, moderate or severe ascites
  • For patients with HCC, inability to undergo disease evaluation with triphasic computed tomography or magnetic resonance imaging because of contrast allergy or other contraindication
  • For patients with HCC, imaging findings consistent with ≥ 50% liver occupation by HCC tumors
  • History of Grade 4 allergic or anaphylactic reaction to any monoclonal antibody therapy or any excipient in the study drugs
  • Surgeries that required general anesthesia must be completed at least 2 weeks before first study drug administration
  • Prior autologous stem cell transplant ≤ 3 months before the first dose
  • Prior allogeneic hematopoietic cell transplant within 6 months of the first dose or with a history of or current clinical Graft-Versus-Host Disease
  • Has had an allogenic tissue/solid organ transplant
  • Other unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition, uncontrolled diabetes) 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

Locations

  • UCSF Medical Center - Helen Diller Family Comprehensive Cancer Center accepting new patients
    San Francisco California 94143 United States
  • City of Hope accepting new patients
    Duarte California 91010 United States

Lead Scientist at UC Cancer

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Surface Oncology
ID
NCT04374877
Phase
Phase 1
Study Type
Interventional
Last Updated