<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03037645</url>
  </required_header>
  <id_info>
    <org_study_id>062-HEM-102</org_study_id>
    <nct_id>NCT03037645</nct_id>
  </id_info>
  <brief_title>Safety, PK, PD, and Antitumor Activity of Vecabrutinib (SNS-062) in B Lymphoid Cancers</brief_title>
  <official_title>A Phase 1b/2 Dose-Escalation and Cohort-Expansion Study of the Noncovalent, Reversible Bruton's Tyrosine Kinase Inhibitor, SNS-062, in Patients With B-Lymphoid Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sunesis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sunesis Pharmaceuticals</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label Phase 1b/2 study in patients with chronic lymphocytic leukemia/small&#xD;
      lymphocytic lymphoma (CLL/SLL)or non hodgkin's lymphoma (NHL) who have failed prior standard&#xD;
      of care therapies including a BTK inhibitor where one is approved for the indication.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study includes 2 parts: phase 1 (dose escalation) and phase 2 (cohort expansion) in&#xD;
      patients with CLL/SLL or NHL who have failed prior standard of care therapies including a BTK&#xD;
      inhibitor where one is approved for the indication. NHL indications include&#xD;
      lymphoplasmacytoid lymphoma/Waldenström's macroglobulinemia (LPL/WM), mantle cell lymphoma&#xD;
      (MCL), marginal zone lymphoma (MZL), diffuse large B-cell lymphoma of the activated B-cell&#xD;
      subtype (DLBCL-ABC), and follicular lymphoma (FL). In Phase 1b, cohorts of 3 to 6 patients&#xD;
      are studied at each dose level, starting with 25 mg vecabrutnib BID in oral capsule form.&#xD;
      Following identification of the MTD and/or recommended dose, in Phase 2 only CLL/SLL patients&#xD;
      will be enrolled to expansion cohorts to further characterize the clinical activity, safety,&#xD;
      and pharmacology of vecabrutinib. Cycle length is 4 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Phase 1b portion completed. Sponsor decided not to proceed with P2 portion of study.&#xD;
    Vecabrutinib was very well tolerated, there was insufficient evidence of activity at the doses&#xD;
    tested in the Phase 1b to advance to Phase 2.&#xD;
  </why_stopped>
  <start_date type="Actual">April 28, 2017</start_date>
  <completion_date type="Actual">August 31, 2020</completion_date>
  <primary_completion_date type="Actual">August 31, 2020</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum tolerated dose and/or Recommended dose of SNS-062 (Phase 1b)</measure>
    <time_frame>Up to approximately 21 months</time_frame>
    <description>To determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD)within the tested SNS-062 dose range. The MTD is the highest tested dose level at which ≥6 subjects have been treated and which is associated with a Cycle 1 dose limiting toxicity (DLT) in &lt;33% of the subjects. The RD may be the MTD or may be a lower dose.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Objective Response Rate (ORR) (Phase 2)</measure>
    <time_frame>Up to approximately 36 months</time_frame>
    <description>Phase 2 portion of study measuring ORR and corresponding 90% confidence intervals by cohort. ORR will be defined by disease subtype as the proportion of subjects who achieve CLL/SLL: a CR, CRi, or PR.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety as assessed through reported AEs, SAEs, DLTs and abnormal lab findings (Phase 1b and Phase 2)</measure>
    <time_frame>Up to approximately 36 months</time_frame>
    <description>Type, severity, timing of onset, duration, and relationship to study drug of any TEAEs or abnormalities of laboratory tests, SAEs, DLTs, or AEs leading to study discontinuation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Characterization of Pharmacokinetics (AUC) (Phase 1b and Phase 2)</measure>
    <time_frame>Up to approximately 36 months</time_frame>
    <description>Area Under the Curve (AUC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Characterization of Pharmacokinetics (Cmin,ss) (Phase 1b and Phase 2)</measure>
    <time_frame>Up to approximately 36 months</time_frame>
    <description>Minimum Plasma Concentration During Dosing Interval at Steady-State (Cmin,ss)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Characterization of Pharmacokinetics (Cmax) (Phase 1b and Phase 2)</measure>
    <time_frame>Up to approximately 36 months</time_frame>
    <description>Maximum Plasma Concentration (Cmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Characterization of Pharmacokinetics (Tmax) (Phase 1b and Phase 2)</measure>
    <time_frame>Up to approximately 36 months</time_frame>
    <description>Time of Maximum Plasma Concentration (Tmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preliminary evidence of anti-tumor activity, in terms of Time to Response (TTR) as assessed by the Investigator. (Phase 2)</measure>
    <time_frame>Up to approximately 36 months</time_frame>
    <description>Measure of Time to Response (TTR) as evaluated by standard response and progression criteria for CLL/SLL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preliminary evidence of anti-tumor activity, in terms of Duration of Response (DOR) as assessed by the Investigator. (Phase 2)</measure>
    <time_frame>Up to approximately 36 months</time_frame>
    <description>Measure of Duration of Response (DOR) as evaluated by standard response and progression criteria for CLL/SLL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preliminary evidence of anti-tumor activity, in terms of Response Rate (RR) as assessed by the Investigator. (Phase 2)</measure>
    <time_frame>Up to approximately 36 months</time_frame>
    <description>Measure of Response Rate (RR) as evaluated by standard response and progression criteria for CLL/SLL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preliminary evidence of anti-tumor activity, in terms of Disease Control Rate (DCR) as assessed by the Investigator. (Phase 2)</measure>
    <time_frame>Up to approximately 36 months</time_frame>
    <description>Measure of Disease Control Rate (DCR) as evaluated by standard response and progression criteria for CLL/SLL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preliminary evidence of anti-tumor activity, in terms of Progression-Free Survival (PFS) as assessed by the Investigator. (Phase 2)</measure>
    <time_frame>Up to approximately 36 months</time_frame>
    <description>Measure of Progression-Free Survival (PFS) as evaluated by standard response and progression criteria for CLL/SLL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preliminary evidence of anti-tumor activity, in terms of Overall Survival (OS) as assessed by the Investigator. (Phase 2)</measure>
    <time_frame>Up to approximately 36 months</time_frame>
    <description>Measure of Overall Survival (OS) as evaluated by standard response and progression criteria for CLL/SLL.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">39</enrollment>
  <condition>Chronic Lymphocytic Leukemia</condition>
  <condition>Small Lymphocytic Lymphoma</condition>
  <condition>Lymphoplasmacytoid Lymphoma</condition>
  <condition>Mantle-Cell Lymphoma</condition>
  <condition>Waldenstrom Macroglobulinemia</condition>
  <condition>Diffuse Large B Cell Lymphoma</condition>
  <condition>Follicular Lymphoma</condition>
  <condition>Marginal Zone Lymphoma</condition>
  <arm_group>
    <arm_group_label>Dose escalating cohorts of SNS-062</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sequential groups, 25, 50, 100, 200, 300, 400 and 500 mg twice daily to determine maximum tolerated dose and recommended dose (RD) in the treatment of various hematological cancers followed by expansion of the recommended dose cohort in Phase 2 of the study treating hematological cancers.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SNS-062</intervention_name>
    <description>SNS-062 will be orally administered twice daily and available in capsules containing either 25 mg or 100 mg of active ingredient.</description>
    <arm_group_label>Dose escalating cohorts of SNS-062</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria (Key factors listed):&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group Performance Status of ≤2.&#xD;
&#xD;
          -  Confirmed malignancy with relapsed/refractory disease after ≥2 lines of standard&#xD;
             systemic therapy including prior BTK inhibitor therapy having CLL, LPL/WM, MCL or MZL&#xD;
             and for DLBCL-ABC and FL, after ≥2 lines of standard systemic therapy (Phase 1b). For&#xD;
             Phase 2, CLL/SLL patients with confirmed malignancy with relapsed/refractory disease&#xD;
             after ≥1 line of standard systemic therapy including prior BTK inhibitor therapy&#xD;
&#xD;
          -  Presence of measurable disease through various assessments depending on specific&#xD;
             cancer type.&#xD;
&#xD;
          -  Current medical need for therapy of the B-lymphoid malignancy.&#xD;
&#xD;
        Exclusion Criteria (Key factors listed):&#xD;
&#xD;
          -  Active central nervous system involvement.&#xD;
&#xD;
          -  History of second primary malignancy that has progressed or required systemic&#xD;
             treatment in the past 2 years. Exceptions include: local cancers of the skin, cervix&#xD;
             or breast cancers, non-invasive bladder cancer, hormone sensitive prostate cancer with&#xD;
             stable PSA ≥3 months, and other localized solid tumors in situ/other low risk cancers.&#xD;
&#xD;
          -  Significant cardiovascular disease or electrocardiogram (ECG) abnormalities&#xD;
&#xD;
          -  Ongoing risk for bleeding due to bleeding diathesis, platelet function disorder,&#xD;
             uncontrolled peptic ulcer disease, oral anticoagulation medications.&#xD;
&#xD;
          -  Evidence of uncontrolled systemic bacterial, fungal or viral infections at the start&#xD;
             of drug therapy.&#xD;
&#xD;
          -  Demonstrated intolerance to BTK inhibitor as shown by discontinuation due to adverse&#xD;
             effects.&#xD;
&#xD;
          -  Use of a moderate or strong inhibitor or inducer of CYP3A4 within 7 days prior to&#xD;
             start of study therapy (e.g., some antibiotics, antifungals, anticonvulsants,&#xD;
             grapefruit).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gary Acton, MD</last_name>
    <role>Study Director</role>
    <affiliation>Sunesis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California Irvine Medical Center</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868-3201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC San Diego Moores Cancer Center</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Moffitt Cancer Center and Research Institute</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weill Cornell Medicine</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Willamette Valley Cancer Institute and Research Center</name>
      <address>
        <city>Eugene</city>
        <state>Oregon</state>
        <zip>97401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - Tyler</name>
      <address>
        <city>Tyler</city>
        <state>Texas</state>
        <zip>75702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Swedish Cancer Institute</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fred Hutchinson Cancer Research Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>January 25, 2017</study_first_submitted>
  <study_first_submitted_qc>January 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 31, 2017</study_first_posted>
  <last_update_submitted>October 15, 2020</last_update_submitted>
  <last_update_submitted_qc>October 15, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CLL</keyword>
  <keyword>hematological diseases</keyword>
  <keyword>relapsed</keyword>
  <keyword>cancer</keyword>
  <keyword>malignancy</keyword>
  <keyword>SNS-062</keyword>
  <keyword>B-lymphoid</keyword>
  <keyword>chronic lymphocytic leukemia</keyword>
  <keyword>small lymphocytic lymphoma</keyword>
  <keyword>lymphoplasmacytoid lymphoma</keyword>
  <keyword>Waldenström's macrogloulinemia</keyword>
  <keyword>mantle cell lymphoma</keyword>
  <keyword>SLL</keyword>
  <keyword>LPL</keyword>
  <keyword>WM</keyword>
  <keyword>MCL</keyword>
  <keyword>refractory</keyword>
  <keyword>DLBCL-ABC</keyword>
  <keyword>DLBCL</keyword>
  <keyword>follicular lymphoma</keyword>
  <keyword>diffuse large B-cell lymphoma</keyword>
  <keyword>CLL/SLL</keyword>
  <keyword>MZL</keyword>
  <keyword>marginal zone lymphoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Follicular</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
    <mesh_term>Lymphoma, Mantle-Cell</mesh_term>
    <mesh_term>Lymphoma, B-Cell, Marginal Zone</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
    <mesh_term>Waldenstrom Macroglobulinemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03037645
org study id: 062-HEM-102
nct id: NCT03037645
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is an open-label Phase 1b/2 study in patients with chronic lymphocytic leukemia/small
      lymphocytic lymphoma (CLL/SLL)or non hodgkin's lymphoma (NHL) who have failed prior standard
      of care therapies including a BTK inhibitor where one is approved for the indication.
This study includes 2 parts: phase 1 (dose escalation) and phase 2 (cohort expansion) in
      patients with CLL/SLL or NHL who have failed prior standard of care therapies including a BTK
      inhibitor where one is approved for the indication. NHL indications include
      lymphoplasmacytoid lymphoma/Waldenström's macroglobulinemia (LPL/WM), mantle cell lymphoma
      (MCL), marginal zone lymphoma (MZL), diffuse large B-cell lymphoma of the activated B-cell
      subtype (DLBCL-ABC), and follicular lymphoma (FL). In Phase 1b, cohorts of 3 to 6 patients
      are studied at each dose level, starting with 25 mg vecabrutnib BID in oral capsule form.
      Following identification of the MTD and/or recommended dose, in Phase 2 only CLL/SLL patients
      will be enrolled to expansion cohorts to further characterize the clinical activity, safety,
      and pharmacology of vecabrutinib. Cycle length is 4 weeks.
allocation: N/A
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose and/or Recommended dose of SNS-062 (Phase 1b)
time frame: Up to approximately 21 months
description: To determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD)within the tested SNS-062 dose range. The MTD is the highest tested dose level at which ≥6 subjects have been treated and which is associated with a Cycle 1 dose limiting toxicity (DLT) in <33% of the subjects. The RD may be the MTD or may be a lower dose.
measure: Objective Response Rate (ORR) (Phase 2)
time frame: Up to approximately 36 months
description: Phase 2 portion of study measuring ORR and corresponding 90% confidence intervals by cohort. ORR will be defined by disease subtype as the proportion of subjects who achieve CLL/SLL: a CR, CRi, or PR.
measure: Safety as assessed through reported AEs, SAEs, DLTs and abnormal lab findings (Phase 1b and Phase 2)
time frame: Up to approximately 36 months
description: Type, severity, timing of onset, duration, and relationship to study drug of any TEAEs or abnormalities of laboratory tests, SAEs, DLTs, or AEs leading to study discontinuation.
measure: Characterization of Pharmacokinetics (AUC) (Phase 1b and Phase 2)
time frame: Up to approximately 36 months
description: Area Under the Curve (AUC)
measure: Characterization of Pharmacokinetics (Cmin,ss) (Phase 1b and Phase 2)
time frame: Up to approximately 36 months
description: Minimum Plasma Concentration During Dosing Interval at Steady-State (Cmin,ss)
measure: Characterization of Pharmacokinetics (Cmax) (Phase 1b and Phase 2)
time frame: Up to approximately 36 months
description: Maximum Plasma Concentration (Cmax)
measure: Characterization of Pharmacokinetics (Tmax) (Phase 1b and Phase 2)
time frame: Up to approximately 36 months
description: Time of Maximum Plasma Concentration (Tmax)
measure: Preliminary evidence of anti-tumor activity, in terms of Time to Response (TTR) as assessed by the Investigator. (Phase 2)
time frame: Up to approximately 36 months
description: Measure of Time to Response (TTR) as evaluated by standard response and progression criteria for CLL/SLL.
measure: Preliminary evidence of anti-tumor activity, in terms of Duration of Response (DOR) as assessed by the Investigator. (Phase 2)
time frame: Up to approximately 36 months
description: Measure of Duration of Response (DOR) as evaluated by standard response and progression criteria for CLL/SLL.
measure: Preliminary evidence of anti-tumor activity, in terms of Response Rate (RR) as assessed by the Investigator. (Phase 2)
time frame: Up to approximately 36 months
description: Measure of Response Rate (RR) as evaluated by standard response and progression criteria for CLL/SLL.
measure: Preliminary evidence of anti-tumor activity, in terms of Disease Control Rate (DCR) as assessed by the Investigator. (Phase 2)
time frame: Up to approximately 36 months
description: Measure of Disease Control Rate (DCR) as evaluated by standard response and progression criteria for CLL/SLL.
measure: Preliminary evidence of anti-tumor activity, in terms of Progression-Free Survival (PFS) as assessed by the Investigator. (Phase 2)
time frame: Up to approximately 36 months
description: Measure of Progression-Free Survival (PFS) as evaluated by standard response and progression criteria for CLL/SLL.
measure: Preliminary evidence of anti-tumor activity, in terms of Overall Survival (OS) as assessed by the Investigator. (Phase 2)
time frame: Up to approximately 36 months
description: Measure of Overall Survival (OS) as evaluated by standard response and progression criteria for CLL/SLL.
arm group label: Dose escalating cohorts of SNS-062
arm group type: Experimental
description: Sequential groups, 25, 50, 100, 200, 300, 400 and 500 mg twice daily to determine maximum tolerated dose and recommended dose (RD) in the treatment of various hematological cancers followed by expansion of the recommended dose cohort in Phase 2 of the study treating hematological cancers.
intervention type: Drug
intervention name: SNS-062
description: SNS-062 will be orally administered twice daily and available in capsules containing either 25 mg or 100 mg of active ingredient.
arm group label: Dose escalating cohorts of SNS-062
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gary Acton, MD
role: Study Director
affiliation: Sunesis Pharmaceuticals
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Follicular
mesh term: Leukemia, Lymphoid
mesh term: Lymphoma, B-Cell
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Lymphoma, Mantle-Cell
mesh term: Lymphoma, B-Cell, Marginal Zone
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Waldenstrom Macroglobulinemia
sharing ipd: No