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Study of SRF617 in Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04336098
Recruitment Status : Recruiting
First Posted : April 7, 2020
Last Update Posted : October 14, 2020
Sponsor:
Information provided by (Responsible Party):
Surface Oncology

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Drug: SRF617 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 56 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of SRF617 in Patients With Advanced Solid Tumors
Actual Study Start Date : March 16, 2020
Estimated Primary Completion Date : October 31, 2022
Estimated Study Completion Date : November 30, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
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.

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.
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.




Primary Outcome Measures :
  1. Dose Limiting Toxicity of SRF617 [ Time Frame: Assessed during first 28 days of treatment ]
    Evaluation of dose-limiting toxicity (DLT)


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. Pharmacodynamics of SRF617 [ Time Frame: Up to 24 months ]
    Pharmacodynamics of SRF617 will be evaluated via serum target occupancy.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04336098


Contacts
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Contact: Kristin Brosofsky, MPH 617-714-4096 ext 193 kbrosofsky@surfaceoncology.com

Locations
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United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Tuhin Salam    626-218-6937    tsalam@coh.org   
Principal Investigator: Yan Xing, MD         
The Angeles Clinic and Research Institute Recruiting
Los Angeles, California, United States, 90025
Contact: Saba Mukarram    310-231-2181    smukarram@theangelesclinic.org   
Principal Investigator: Inderjit Mehmi, M.D.         
United States, Texas
South Texas Accelerated Research Therapeutics Recruiting
San Antonio, Texas, United States, 78229
Contact: Angela Galindo    210-593-5202    angela.galindo@startsa.com   
Principal Investigator: Amita Patnaik, MD         
Canada, Ontario
University Health Network-Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Tongtong Chen    (416) 946-4501, ext 2596    tongtong.chen@uhn.ca   
Principal Investigator: Anna Spreafico, MD, PhD         
Sponsors and Collaborators
Surface Oncology
Investigators
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Study Chair: Alison O'Neill, MD Surface Oncology
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Responsible Party: Surface Oncology
ClinicalTrials.gov Identifier: NCT04336098    
Other Study ID Numbers: SRF617-101
First Posted: April 7, 2020    Key Record Dates
Last Update Posted: October 14, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Surface Oncology:
metastatic solid tumors
advanced solid tumors
Phase 1
SRF617
CD39
safety
efficacy
immunotherapy
adenosine pathway
cancer
immuno-oncology
pancreatic cancer
gastric cancer
Additional relevant MeSH terms:
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Neoplasms