Clinical Trials /

Study of SRF388 in Patients With Advanced Solid Tumors

NCT04374877

Description:

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

Related Conditions:
  • Clear Cell Renal Cell Carcinoma
  • Hepatocellular Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of SRF388 in Patients With Advanced Solid Tumors
  • Official Title: A Phase 1 Study of SRF388 in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: SRF388-101
  • NCT ID: NCT04374877

Conditions

  • Advanced Solid Tumor
  • Clear Cell Renal Cell Carcinoma
  • Hepatocellular Carcinoma

Interventions

DrugSynonymsArms
SRF388Part A Monotherapy Expansion

Purpose

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

Detailed Description

      This is a Phase 1, open-label, first-in-human (FIH), dose-escalation monotherapy, safety, and
      expansion study of SRF388, a monoclonal antibody targeting IL-27, that will be conducted in 3
      parts:

        -  Part A: SRF388 monotherapy dose-escalation cohort in patients with advanced solid
           tumors.

        -  Part B: SRF388 monotherapy clear cell renal cell carcinoma (ccRCC) expansion cohort is a
           safety, efficacy, and tumor biopsy expansion portion of the study in patients with
           advanced or metastatic ccRCC to further examine the safety, pharmacokinetics (PK),
           pharmacodynamics, and efficacy of SRF388 as a monotherapy.

        -  Part C: SRF388 monotherapy hepatocellular carcinoma (HCC) safety expansion cohort is a
           safety expansion portion of the study in patients with advanced or metastatic HCC to
           further examine the safety, PK, pharmacodynamics, and preliminary efficacy of SRF388 as
           a monotherapy.
    

Trial Arms

NameTypeDescriptionInterventions
Part A Monotherapy ExpansionExperimentalThe Part A monotherapy dose escalation portion of the study will evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary efficacy of SRF388 as monotherapy in up to 42 patients with advanced solid tumors.
  • SRF388
Part B Monotherapy ccRCC ExpansionExperimentalPart B monotherapy ccRCC expansion will evaluate the safety, tolerability, PK, pharmacodynamics, and efficacy of SRF388 monotherapy at the recommended phase 2 dose (RP2D) in up to 40 patients with ccRCC (any clear cell component in the histologic definition).
  • SRF388
Part C SRF388 Monotherapy HCC Safety ExpansionExperimentalPart C montherapy HCC expansion will evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary efficacy of SRF388 in approximately 10 patients with HCC.
  • SRF388

Eligibility Criteria

        Abbreviated Inclusion Criteria:

          1. ≥ 18 years of age

          2. Locally advanced or metastatic (Stage IV) solid tumor which has progressed during or
             after standard therapy, and for whom no appropriate therapies are available (based on
             investigator judgment)

          3. For patients in Part B, must have metastatic ccRCC with at least 1 measurable lesion
             per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

          4. For patients in Part C, patients must have unresectable HCC, Barcelona Clinic Liver
             Cancer (BCLC1) Stage B (not eligible for transcatheter arterial chemoembolization
             [TACE]) or Stage C with at least 1 measurable lesion per RECIST 1.1

          5. For patients in Part B, demonstrated 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 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.

          6. For patients in Part C, demonstrated PD during or after the most recent treatment
             regimen. Prior treatment history must include progression during or after treatment
             with a tyrosine kinase inhibitor.

          7. Appropriate candidate for and willing to undergo pretreatment and on-treatment tumor
             biopsies (Part A and Part B only, if in the applicable group)

          8. Serum creatinine clearance ≥ 50 mL/min per Cockcroft-Gault formula or serum creatinine
             ≤ 2.0 x the upper limit of normal (ULN)

          9. Total bilirubin ≤ 1.5 x ULN (≤ 3 x ULN if elevated because of Gilbert's syndrome and ≤
             2 x ULN for patients in Part C)

         10. Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) < 2.5 x
             ULN (< 5 x ULN if liver metastasis or for patients in Part C)

         11. For patients in Part C, Child-Pugh class A or B7 with a serum albumin ≥ 2.8 g/dL (≥ 28
             g/L)

         12. Adequate hematologic function, defined as ANC ≥ 1.0 x 109/L, hemoglobin ≥ 9.0 g/dL,
             and platelet count ≥ 100 x 109/L

         13. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

        Abbreviated Exclusion Criteria:

          1. Previously received an anti-IL27 antibody or anti-IL27 targeted therapy

          2. For patients in Part B, non-clear cell RCC histology

          3. For patients in Part C, fibrolamellar or mixed hepatocellular cholangiocarcinoma

          4. History of ≥ Grade 4 allergic or anaphylactic reaction to any monoclonal antibody
             therapy or any excipient in the study drugs

          5. Major surgery within 4 weeks prior to Screening

          6. 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:[Part A] Dose Limiting Toxicity of SRF388
Time Frame:Assessed during first 28 days of treatment
Safety Issue:
Description:Evaluation of dose-limiting toxicity (DLT)

Secondary Outcome Measures

Measure:[Part A, Part B] Safety Analysis: Summary of adverse events (AEs) and based on treatment-emergent AEs (TEAEs)
Time Frame:Up to 24 months
Safety Issue:
Description:Safety and tolerability of SRF388 will be assessed by summarizing adverse events (AEs) and will be based on treatment-emergent AEs (TEAEs). A TEAE is an AE that emerges or worsens in the period from the first dose of study treatment to 30 days after the last dose of study drug assessed by per CTCAE version 5.0 or higher.
Measure:[Part A, Part B, Part C] Pharmocokinetics (PK) of SRF388
Time Frame:Up to 24 months
Safety Issue:
Description:Serum concentrations of SRF388 will be collected and analyzed to evaluate the PK of SRF388.
Measure:[Part A, Part B, Part C] Pharmacodynamics of SRF388 (pSTAT levels)
Time Frame:Up to 24 months
Safety Issue:
Description:Pharmacodynamics of SRF388 will be evaluated in immune cell subsets via whole blood.
Measure:[Part A, Part C] Objective response rate (ORR)
Time Frame:Up to 24 months
Safety Issue:
Description:ORR will be estimated by the percentage of patients achieving a best overall response of CR or PR per iRECIST.
Measure:[Part A, Part B, Part C] Duration of response (DoR)
Time Frame:Up to 24 months
Safety Issue:
Description:DoR is defined as the time from the first documented response (CR or PR) to documented disease progression as determined by applicable disease criteria, or documented death due to any cause, whichever occurs first.
Measure:[Part A, Part B, Part C] Disease control rate (DCR)
Time Frame:Up to 24 months
Safety Issue:
Description:DCR is defined as the percentage of patients with CR, partial PR, or stable disease lasting a minimum of 12 weeks.
Measure:[Part A, Part B, Part C] Progression-free survival (PFS)
Time Frame:Up to 24 months
Safety Issue:
Description:PFS is defined as the time from the first treatment on study with study drug to documented disease progression as determined by applicable disease criteria or death.
Measure:[Part B] Effect of SRF388 on intratumoral cytokine expression
Time Frame:Up to 24 months
Safety Issue:
Description:Levels of intratumoral cytokine expression will be evaluated in patients undergoing pretreatment and on-treatment tumor biopsies via serum.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Surface Oncology

Trial Keywords

  • metastatic solid tumors
  • advanced solid tumors
  • Phase 1
  • SRF388
  • IL-27
  • safety
  • efficacy
  • immunotherapy
  • cancer
  • immuno-oncology
  • kidney cancer
  • renal cell carcinoma
  • liver cancer
  • hepatocellular carcinoma

Last Updated

April 30, 2020