Clinical Trials /

Study of SRF617 in Patients With Advanced Solid Tumors

NCT04336098

Description:

A Phase 1, first-in-human, dose escalation, safety, and tumor biopsy expansion study of SRF617, an antibody that inhibits CD39 activity, in patients with advanced solid tumors. Inhibition of CD39 activity may improve the ability to mount an immune response against tumor cells.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of SRF617 in Patients With Advanced Solid Tumors
  • Official Title: A Phase 1 Study of SRF617 in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: SRF617-101
  • NCT ID: NCT04336098

Conditions

  • Advanced Solid Tumor

Interventions

DrugSynonymsArms
SRF617Monotherapy Dose Escalation

Purpose

A Phase 1, first-in-human, dose escalation, safety, and tumor biopsy expansion study of SRF617, an antibody that inhibits CD39 activity, in patients with advanced solid tumors. Inhibition of CD39 activity may improve the ability to mount an immune response against tumor cells.

Detailed Description

      A Phase 1, open-label, first-in-human, monotherapy dose escalation, safety, and tumor biopsy
      expansion study of SRF617 in patients with advanced solid tumors. The monotherapy dose
      escalation portion of the study will evaluate the safety, tolerability, pharmacokinetics
      (PK), pharmacodynamics, and preliminary efficacy of SRF617 as monotherapy in patients with
      advanced solid tumors. The monotherapy tumor biopsy expansion portion of the study will
      further evaluate the safety and intratumoral pharmacodynamics of SRF617 monotherapy.
    

Trial Arms

NameTypeDescriptionInterventions
Monotherapy Dose EscalationExperimentalThe monotherapy dose escalation portion of the study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of SRF617 as monotherapy in up to 36 patients with advanced solid tumors.
  • SRF617
Monotherapy Tumor Biopsy ExpansionExperimentalThe monotherapy tumor biopsy expansion portion of the study will further evaluate the safety and intratumoral pharmacodynamics of SRF617 monotherapy in up to 20 patients at cleared and recommended phase 2 dose levels.
  • SRF617

Eligibility Criteria

        Abbreviated Inclusion Criteria:

          1. ≥ 18 years of age

          2. Experienced disease progression during or after standard therapy or were intolerant of
             standard therapy, and for whom no appropriate therapies are available (based on the
             judgment of the Investigator)

          3. Histological or cytological evidence of advanced, relapsed, or refractory solid tumor
             cancer that is not a candidate for curative therapy

          4. Have tumor tissue that is accessible for pretreatment and on treatment biopsy in the
             opinion of the Investigator and be willing to undergo pretreatment and on-treatment
             biopsies per protocol (for patients in the monotherapy tumor biopsy expansion cohort
             only)

          5. Adequate renal function, defined as serum creatinine clearance ≥ 30 mL/min per
             Cockcroft-Gault formula

          6. Total bilirubin ≤ 1.5 x ULN (≤ 3 x ULN if elevated because of Gilbert's syndrome)

          7. Aspartate aminotransferase and alanine aminotransferase < 2.5 x ULN (< 5 x ULN if
             liver metastasis is present)

          8. Adequate hematologic function, defined as absolute neutrophil count (ANC) ≥ 1.0 x
             109/L, hemoglobin ≥ 8.0 g/dL, and platelet count ≥ 75 x 109/L. Blood cell transfusion
             to meet enrollment criteria is not allowed.

          9. Eastern Cooperative Oncology Group performance status of 0 to 1

        Abbreviated Exclusion Criteria:

          1. Previously received an anti-CD39 antibody or anti-CD39 targeted therapy

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

          3. Major surgery within 4 weeks before Screening

          4. 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:Dose Limiting Toxicity of SRF617
Time Frame:Assessed during first 28 days of treatment
Safety Issue:
Description:Evaluation of dose-limiting toxicity (DLT)

Secondary Outcome Measures

Measure: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 SRF617 monotherapy 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:Pharmocokinetics (PK) of SRF617
Time Frame:Up to 24 months
Safety Issue:
Description:Serum concentrations of SRF617 will be collected and analyzed to evaluate the PK of SRF617.
Measure:Pharmacodynamics of SRF617
Time Frame:Up to 24 months
Safety Issue:
Description:Pharmacodynamics of SRF617 will be evaluated via serum target occupancy.
Measure:Objective response rate (ORR)
Time Frame:Up to 24 momths
Safety Issue:
Description:ORR will be estimated by the percentage of patients achieving a best overall response of CR or PR per iRECIST.
Measure: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: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: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:Landmark PFS rate
Time Frame:Up to 24 months
Safety Issue:
Description:Landmark PFS is defined as the percentage of patients who have not developed PFS events (ie, death or documented disease progression as determined by applicable disease criteria) at 6 months, 1 year, 1.5 years, and 2 years.
Measure:Effect of SRF617 on intratumoral CD39 enzymatic activity
Time Frame:Up to 24 months
Safety Issue:
Description:Levels of intratumoral CD39 enzymatic activity will be evaluated in patients receiving pretreatment and on-treatment tumor biopsies via an in situ ATPase histochemistry assay.

Details

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

Trial Keywords

  • metastatic solid tumors
  • advanced solid tumors
  • Phase 1
  • SRF617
  • CD39
  • safety
  • efficacy
  • immunotherapy
  • adenosine pathway
  • cancer
  • immuno-oncology
  • pancreatic cancer
  • gastric cancer

Last Updated

April 2, 2020