Study of SRF617 in Patients With Advanced Solid Tumors

Overview

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.

Full Title of Study: “A Phase 1 Study of SRF617 in Patients With Advanced Solid Tumors”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: October 31, 2022

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.

Interventions

  • Drug: SRF617
    • SRF617 prevents CD39 mediated conversion of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) to adenosine monophosphate (AMP) and phosphate, leading to an increase in extracellular ATP and a reduction in adenosine levels within the tumor microenvironment (TME). There is an important role for extracellular ATP and adenosine in cancer maintenance and progression, and maintaining high levels of ATP (and low levels of adenosine) in the TME may have anticancer therapeutic activity.

Arms, Groups and Cohorts

  • Experimental: Monotherapy Dose Escalation
    • The 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.
  • Experimental: Monotherapy Tumor Biopsy Expansion
    • The 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.

Clinical Trial Outcome Measures

Primary Measures

  • Dose Limiting Toxicity of SRF617
    • Time Frame: Assessed during first 28 days of treatment
    • Evaluation of dose-limiting toxicity (DLT)

Secondary Measures

  • Safety Analysis: Summary of adverse events (AEs) and based on treatment-emergent AEs (TEAEs)
    • Time Frame: Up to 24 months
    • 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.
  • Pharmacokinetics (PK) of SRF617
    • Time Frame: Up to 24 months
    • Serum concentrations of SRF617 will be collected and analyzed to evaluate the PK of SRF617.
  • Pharmacodynamics of SRF617
    • Time Frame: Up to 24 months
    • Pharmacodynamics of SRF617 will be evaluated via serum target occupancy.
  • Objective response rate (ORR)
    • Time Frame: Up to 24 months
    • ORR will be estimated by the percentage of patients achieving a best overall response of CR or PR per iRECIST.
  • Duration of response (DoR)
    • Time Frame: Up to 24 months
    • 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.
  • Disease control rate (DCR)
    • Time Frame: Up to 24 months
    • DCR is defined as the percentage of patients with CR, partial PR, or stable disease lasting a minimum of 12 weeks.
  • Progression-free survival (PFS)
    • Time Frame: Up to 24 months
    • 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.
  • Landmark PFS rate
    • Time Frame: Up to 24 months
    • 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.
  • Effect of SRF617 on intratumoral CD39 enzymatic activity
    • Time Frame: Up to 24 months
    • 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.

Participating in This Clinical Trial

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 upper limit of normal (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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Surface Oncology
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Alison O’Neill, MD, Study Chair, Surface Oncology
  • Overall Contact(s)
    • Kristin Brosofsky, MPH, 617-714-4096, kbrosofsky@surfaceoncology.com

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