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Trial record 1 of 1 for:    SRF617-101
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Study of SRF617 in Patients With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT04336098
Recruitment Status : Recruiting
First Posted : April 7, 2020
Last Update Posted : February 21, 2022
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Surface Oncology

Brief Summary:
A Phase 1, first-in-human, monotherapy and combination dose escalation and expansion study of SRF617.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Drug: SRF617 Drug: Gemcitabine Drug: Albumin-Bound Paclitaxel Drug: Pembrolizumab Phase 1

Detailed Description:
A Phase 1, open-label, first-in-human, study of SRF617, consisting of a monotherapy dose escalation, a monotherapy tumor biopsy expansion, combination dose escalations, and combination safety and efficacy expansions that will enroll patients with advanced solid tumors. The monotherapy dose escalation portion of the study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), 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. The combination therapy dose escalation portion of the study will evaluate the safety, tolerability, PK, and preliminary efficacy of SRF617 in combination with gemcitabine + albumin-bound paclitaxel, or SRF617 in combination with pembrolizumab, in patients with locally advanced or metastatic solid tumors. Once the SRF617 combination recommended Phase 2 doses are established, additional patients with select solid tumors may be enrolled in the respective combination expansion arm of the study. An additional quadruplet combination will also be explored in patients with advanced first line (1L) PDAC (i.e., SRF617 + pembrolizumab + gemcitabine + albumin-bound paclitaxel).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 177 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.

Experimental: Combination Therapy - SRF617 with Gemcitabine + Albumin-bound Paclitaxel Dose Escalation
This portion of the study will evaluate the safety, tolerability, PK, and preliminary efficacy of SRF617 in combination with gemcitabine + albumin-bound paclitaxel in patients with locally advanced or metastatic 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.

Drug: Gemcitabine
Gemcitabine as an intravenous (IV) infusion

Drug: Albumin-Bound Paclitaxel
Albumin-bound paclitaxel as an IV infusion
Other Name: Abraxane®

Experimental: Combination Therapy - SRF617 with Pembrolizumab Dose Escalation
This portion of the study will evaluate the safety, tolerability, PK, and preliminary efficacy of SRF617 in combination with pembrolizumab (Keytruda®) in patients with locally advanced or metastatic 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.

Drug: Pembrolizumab
Pembrolizumab as an IV infusion .
Other Name: Keytruda®

Experimental: Combination Therapy - SRF617 with Gemcitabine + Albumin-bound Paclitaxel Dose Expansion
Enrollment at the recommended phase 2 combination dose may be expanded to include approximately 10 additional patients with advanced pancreatic ductal adenocarcinoma (PDAC) to further evaluate safety with SRF617 and gemcitabine + albumin-bound paclitaxel combination therapy.
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.

Drug: Gemcitabine
Gemcitabine as an intravenous (IV) infusion

Drug: Albumin-Bound Paclitaxel
Albumin-bound paclitaxel as an IV infusion
Other Name: Abraxane®

Experimental: Combination Therapy - SRF617 with Pembrolizumab Dose Expansion GC/GEJ
Enrollment at the recommended phase 2 combination dose may be expanded to include approximately 28 additional patients with 2 anti-PD-(L) 1 naive HER2 negative gastric cancer (GC) or gastroesophageal junction (GEJ) adenocarcinoma to further evaluate safety with SRF617 and pembrolizumab combination therapy.
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.

Drug: Pembrolizumab
Pembrolizumab as an IV infusion .
Other Name: Keytruda®

Experimental: SRF617 + Pembrolizumab + Gemcitabine + Albumin-bound Paclitaxel Quadruplet Dose Expansion
Enrollment at the recommended phase 2 combination dose established in the combination dose escalation arms (if recommended phase 2 combination doses differ, the lower of the starting 2 doses will be used) may be expanded to include up to approximately 30 additional patients with advanced 1L PDAC.
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.

Drug: Gemcitabine
Gemcitabine as an intravenous (IV) infusion

Drug: Albumin-Bound Paclitaxel
Albumin-bound paclitaxel as an IV infusion
Other Name: Abraxane®

Drug: Pembrolizumab
Pembrolizumab as an IV infusion .
Other Name: Keytruda®

Experimental: Combination Therapy - SRF617 with Pembrolizumab Dose Expansion anti-PD-L1 GC/GEJ, PD-L1+ NSCLC
Enrollment at the recommended phase 2 combination dose may be expanded to include approximately 29 additional patients with anti-PD-(L) 1 relapsed/refractory PD-L1+ HER2 negative gastric cancer (GC) or gastroesophageal junction (GEJ) adenocarcinoma or advanced PD-L1+ NSCLC to further evaluate safety with SRF617 and pembrolizumab combination therapy.
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.

Drug: Pembrolizumab
Pembrolizumab as an IV infusion .
Other Name: Keytruda®




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 and combination therapy 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 drug 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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. Be ≥ 18 years of age on day of signing the informed consent
  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). (Exception: PDAC patients in 1L combination expansion arms.)
  3. Histological or cytological evidence of advanced, relapsed, or refractory solid tumor cancer that is not a candidate for curative therapy
  4. For all patients in the combination expansion arms, have at least 1 lesion that is measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by local site Investigator/radiology. The measurable lesion must be outside of a radiation field if the participant received prior radiation. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  5. 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 arm only).
  6. Adequate renal function
  7. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (≤ 3 x ULN if elevated because of Gilbert's syndrome); patients to be treated with SRF617 in combination with albumin-bound paclitaxel must have total bilirubin ≤ 1.5 × ULN)
  8. Aspartate aminotransferase and alanine aminotransferase < 2.5 x ULN (< 5 x ULN if liver metastasis is present)
  9. 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
  10. Prothrombin time (PT) or international normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless the patient is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
  11. Eastern Cooperative Oncology Group performance status of 0 to 1
  12. For the SRF617 + gemcitabine + albumin-bound paclitaxel expansion arm and SRF617 + pembrolizumab + gemcitabine + albumin-bound paclitaxel quadruplet expansion arm enrolling patients with 1L PDAC only:

    1. Patients with confirmed advanced PDAC naive to any prior systemic treatment
    2. Prior neoadjuvant or adjuvant therapy for PDAC is permitted if neoadjuvant or adjuvant therapy was completed at least 6 months prior to study enrollment. Prior pembrolizumab treatment is not allowed if patient is enrolling in the quadruplet expansion arm.
    3. Patients initially diagnosed with locally advanced PDAC who have undergone chemotherapy then resection and had no evidence of disease are eligible if relapsed or metastatic disease has occurred and if the last dose of chemotherapy was received more than 6 months before study entry
  13. For the anti-PD-(L) 1 naïve SRF617+ pembrolizumab combination expansion arm only:

    1. Patients with unresectable locally advanced or metastatic HER2 GEJ who have received a maximum of 2 prior lines of anticancer therapy
    2. Patients must be anti PD(L)-1 treatment naïve
  14. For the anti-PD-(L) 1 relapsed/refractor SRF617 + pembrolizumab expansion arm only:

    1. Patients with unresectable locally advanced or metastatic HER2- GC or GEJ adenocarcinoma or unresectable advanced or metastatic NSCLC whose disease is PD-L1+ (defined as CPS ≥ 1 or TPS ≥ 1%).
    2. Must have received at least 1 prior line of systemic anticancer therapy and no more than 4 prior lines of systemic anticancer therapy
    3. Must have anti-PD-(L) 1 relapsed/refractory diseased defined as having progressed on treatment and with anti-PD-(L)1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other immune checkpoint inhibitors or other therapies.
  15. 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 treatment period (or beginning 14 days before the initiation of pembrolizumab for oral contraception), including 30 days after the last dose of SRF617, or 120 days after the last dose of pembrolizumab for patients in the pembrolizumab combination arms; 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 women of child-bearing potential (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.

Abbreviated Exclusion Criteria:

  1. Previously received an anti-CD39 antibody or anti-CD39 targeted therapy. In combination expansion arms, patients cannot have previously received agents that inhibit CD73, A2AR, or A2BR.
  2. History of Grade 3 allergic or anaphylactic reaction to any monoclonal antibody therapy (mAb), 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
  5. For patients in the anti-PD-(L) 1 naïve SRF617 + pembrolizumab combination expansion arm only:

    1. Discontinuation from previous therapy with an anti programmed cell death ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40, CD137) due to a ≥ Grade 3 immune-related AE
    2. Prior therapy with anti-PD-1 or anti-PD-L1 agents is not permitted
  6. Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 21 days before the first dose of study drug Note: Patients who have entered the follow-up phase of an investigational study may participate if it has been at least 21 days after the last dose of the previous investigational agent
  7. Received prior radiotherapy within 2 weeks of start of study treatment. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-central nervous system disease.
  8. Has received radiation therapy to the lung that is >30Gy within 6 months of the first dose of study treatment
  9. Current pneumonitis or history of (non-infectious) pneumonitis requiring steroids

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: Roger Lis 339-337-4213 rlis@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, Colorado
University of Colorado Recruiting
Aurora, Colorado, United States, 80045-2517
Contact: Ciara D'Amico    720-848-4604    ciara.damico@cuanschutz.edu   
Principal Investigator: Sunnie Kim, MD         
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Lauren Ponto       Lauren.Ponto@moffitt.org   
Principal Investigator: Rutika Mehta, MD         
United States, Texas
Mary Crowley Cancer Research Recruiting
Dallas, Texas, United States, 75251
Contact: Terrell Martinez    214-658-1946    tmartinez@marycrowley.org   
Principal Investigator: James Strauss, M.D.         
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         
United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22903
Contact: DeJuana Coleman    434-924-9199    evq9yw@hscmail.mcc.virginia.edu   
Principal Investigator: Matthew Reilley, MD         
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98109-1023
Contact: Erin Shaw       eshaw@seattlecca.org   
Principal Investigator: Andrew Coveler, 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         
Canada, Quebec
Universite de Montreal - Centre Hospitalier de l'Universite de Montreal (CHUM) - Hopital Notre-Dame Recruiting
Montréal, Quebec, Canada, H2X 0C1
Contact: Arnaud Villier    514-890-8000 ext 26047    arnaud.villier.chum@ssss.gouv.qc.ca   
Principal Investigator: Rahima Jamal, MD         
Sponsors and Collaborators
Surface Oncology
Merck Sharp & Dohme LLC
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
KEYNOTE-A62 ( Other Identifier: Merck Sharp & Dohme Corp. )
First Posted: April 7, 2020    Key Record Dates
Last Update Posted: February 21, 2022
Last Verified: February 2022
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
pembrolizumab
Keytruda®
gemcitabine
albumin-bound paclitaxel
Abraxane®
nab-paclitaxel
gastroesophageal junction adenocarcinoma
GEJ
PD-1
NSCLC
lung cancer
Additional relevant MeSH terms:
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Neoplasms
Gemcitabine
Paclitaxel
Pembrolizumab
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological