<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/NCT04502706</url>
  </required_header>
  <id_info>
    <org_study_id>SRP001</org_study_id>
    <nct_id>NCT04502706</nct_id>
  </id_info>
  <brief_title>Study of GS-0189 (Formerly FSI-189) as Monotherapy and in Combination With Rituximab in Participants With Relapsed/Refractory Non-Hodgkin Lymphoma</brief_title>
  <official_title>A Phase 1 Study of GS-0189 (Formerly FSI-189) as Monotherapy and in Combination With Rituximab in Patients With Relapsed/Refractory Non-Hodgkin Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Gilead Sciences</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>
      The primary objective of this study is to determine the safety and tolerability of GS-0189&#xD;
      (formerly FSI-189) as monotherapy and in combination with rituximab in participants with&#xD;
      relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will consist of 5 parts: 1) an initial Monotherapy Dose Escalation (MDE) part, 2) a&#xD;
      Combination Dose Escalation (CDE) part, 3) a Pharmacokinetic (PK) Evaluation part, 4) an&#xD;
      Alternate Schedule Evaluation (ASE) part and 5) a diffuse large B-cell lymphoma (DLBCL)&#xD;
      Expansion part.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Sponsor's decision to discontinue development of this molecule&#xD;
  </why_stopped>
  <start_date type="Actual">November 17, 2020</start_date>
  <completion_date type="Actual">March 31, 2022</completion_date>
  <primary_completion_date type="Actual">March 31, 2022</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants Experiencing Treatment-Emergent Adverse Events</measure>
    <time_frame>Up to 11 months</time_frame>
    <description>Adverse events as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Experiencing Laboratory Abnormalities</measure>
    <time_frame>Up to 11 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic (PK) Parameter: AUClast of GS-0189</measure>
    <time_frame>Up to 11 months</time_frame>
    <description>AUClast is defined as the concentration of drug from time zero to the last observable concentration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK Parameter: AUCtau of GS-0189</measure>
    <time_frame>Up to 11 months</time_frame>
    <description>AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK Parameter: Cmax of GS-0189</measure>
    <time_frame>Up to 11 months</time_frame>
    <description>Cmax is defined as the maximum observed concentration of drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK Parameter: Accumulation Ratio (AR) of GS-0189</measure>
    <time_frame>Up to 11 months</time_frame>
    <description>AR is defined as ratio based on Cmax and AUCtau after first dose and after multiple doses.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK Parameter: Tmax of GS-0189</measure>
    <time_frame>Up to 11 months</time_frame>
    <description>Tmax is defined as the time (observed time point) of Cmax.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK Parameter: AUC0-tau/D Dose-normalized AUCtau of GS-0189</measure>
    <time_frame>Up to 11 months</time_frame>
    <description>AUC0-tau/D is defined dose normalized area under the concentration-time curve from time zero (pre dose time point of the infusion) to the end of the dosing interval.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Signal Regulatory Protein Alpha (SIRPα) Receptor Occupancy in the Blood</measure>
    <time_frame>Up to 11 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Concentration of GS-0189</measure>
    <time_frame>Up to 11 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Anti-GS-0189 Antibody Positivity</measure>
    <time_frame>Up to 11 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) as assessed by Lugano Classification response criteria for lymphomas.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>DOR is defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of disease progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>PFS is defined as the interval from the first dose date of drug to the earlier of the first documentation of definitive disease progression or death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>OS is defined as the interval from the first dose date of drug to death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Progression (TTP)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>TTP is defined as the interval from the first dose date of drug to the earlier of the first documentation of definitive disease progression.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Non-hodgkin Lymphoma</condition>
  <arm_group>
    <arm_group_label>GS-0189 (Monotherapy Dose Escalation, MDE)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) participants will receive GS-0189 doses of 10, 30, or 100 mg every 2 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GS-0189 + Rituximab (Combination Dose Escalation, CDE)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>R/R NHL participants will receive GS-0189 doses of 100, 300, 1000, 2000, and 3000 mg in combination with rituximab at 375 mg/m^2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GS-0189 + Rituximab (Pharmacokinetic (PK) Evaluation)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>R/R NHL participants will receive GS-0189 dose of up to 30 mg followed by the highest designated safe dose from the Combination Dose Escalation cohort (CDE) in combination with rituximab at 375 mg/m^2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GS-0189 + Rituximab (Alternate Schedule Evaluation, ASE)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>R/R NHL participants will receive GS-0189 every 4 weeks in combination with rituximab 375 mg/m^2. The GS-0189 dose will be determined based on the totality of safety, PK, and pharmacodynamic (PD) data from the preceding cohorts.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GS-0189 + Rituximab (DLBCL Expansion)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Diffuse large B-cell lymphoma (DLBCL) participants will receive GS-0189 in combination with rituximab 375 mg/m^2. The GS-0189 dose will be determined based on the totality of safety, PK, and PD data from the preceding cohorts.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GS-0189</intervention_name>
    <description>GS-0189 will be administered intravenously.</description>
    <arm_group_label>GS-0189 (Monotherapy Dose Escalation, MDE)</arm_group_label>
    <arm_group_label>GS-0189 + Rituximab (Alternate Schedule Evaluation, ASE)</arm_group_label>
    <arm_group_label>GS-0189 + Rituximab (Combination Dose Escalation, CDE)</arm_group_label>
    <arm_group_label>GS-0189 + Rituximab (DLBCL Expansion)</arm_group_label>
    <arm_group_label>GS-0189 + Rituximab (Pharmacokinetic (PK) Evaluation)</arm_group_label>
    <other_name>FSI-189</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rituximab</intervention_name>
    <description>Rituximab will be administered intravenously.</description>
    <arm_group_label>GS-0189 + Rituximab (Alternate Schedule Evaluation, ASE)</arm_group_label>
    <arm_group_label>GS-0189 + Rituximab (Combination Dose Escalation, CDE)</arm_group_label>
    <arm_group_label>GS-0189 + Rituximab (DLBCL Expansion)</arm_group_label>
    <arm_group_label>GS-0189 + Rituximab (Pharmacokinetic (PK) Evaluation)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  DLBCL, follicular lymphoma (FL), mantle cell lymphoma (MCL), or marginal zone lymphoma&#xD;
             (MZL) relapsed/refractory (R/R) to at least 2 prior lines of therapy. Prior autologous&#xD;
             hematopoietic cell transplantation and individuals with transformed lymphomas are&#xD;
             permitted. Individuals must be at least 3 months out from prior autologous&#xD;
             hematopoietic cell transplantation. Individuals with indolent lymphomas must be&#xD;
             candidates for systemic treatment in the judgment of the treating physician.&#xD;
&#xD;
          -  In the DLBCL Expansion part: DLBCL that is relapsed or refractory to at least 2 prior&#xD;
             lines of therapy. Prior autologous hematopoietic cell transplantation and individuals&#xD;
             with transformed lymphomas are permitted.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) score of 0 to 2.&#xD;
&#xD;
          -  For the DLBCL expansion cohort, disease must be measurable for response per Lugano&#xD;
             criteria. For all other cohorts, disease must be measurable or assessable for response&#xD;
             per Lugano criteria.&#xD;
&#xD;
          -  Exhibit acceptable hematopoietic, liver, renal, and coagulation function as assessed&#xD;
             by laboratory tests.&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Individuals with active brain metastases (Individuals with stable treated central&#xD;
             nervous system (CNS) lesions who are off corticosteroid therapy for at least 3 weeks&#xD;
             are not considered active.&#xD;
&#xD;
          -  Individuals with Burkitt's lymphoma.&#xD;
&#xD;
          -  Prior treatment with a chimeric antigen receptor (CAR) T-cell therapy ≤ 90 days from&#xD;
             first dose of study drug.&#xD;
&#xD;
          -  Prior allogeneic stem cell transplant.&#xD;
&#xD;
          -  Previous anticancer therapy including chemotherapy, hormonal therapy, and&#xD;
             investigational agents within 3 weeks or at least 4 half-lives (up to a maximum of 4&#xD;
             weeks), whichever is longer, prior to first dose of study drug.&#xD;
&#xD;
          -  Known active or chronic hepatitis B or C infection or human immunodeficiency virus.&#xD;
&#xD;
          -  Prior treatment with CD47 or signal regulatory protein alpha (SIRPα)-targeting agents.&#xD;
&#xD;
          -  Hypersensitivity to the active substance, to murine proteins, or to any of the other&#xD;
             excipients of rituximab&#xD;
&#xD;
          -  Significant medical diseases or conditions, as assessed by the Investigator and&#xD;
             Sponsor, that would substantially increase the risk:benefit ratio of participating in&#xD;
             the study.&#xD;
&#xD;
          -  Rituximab-containing cohorts only: Receipt of live/attenuated vaccines within 30 days&#xD;
             of rituximab dosing&#xD;
&#xD;
          -  Has persisting toxicity related to prior therapy of Grade &gt; 1 in severity per National&#xD;
             Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version&#xD;
             5.0.&#xD;
&#xD;
        Note: Other protocol defined Inclusion/Exclusion criteria may apply.&#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>Gilead Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Gilead Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama Comprehensive Cancer Center</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35233</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City of Hope</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists</name>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Oklahoma Health Sciences Center</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.gileadclinicaltrials.com/study/?id=SRP001</url>
    <description>Gilead Clinical Trials Website</description>
  </link>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>July 16, 2020</study_first_submitted>
  <study_first_submitted_qc>August 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <last_update_submitted>June 1, 2023</last_update_submitted>
  <last_update_submitted_qc>June 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 5, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rituximab</mesh_term>
  </intervention_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/NCT04502706
org study id: SRP001
nct id: NCT04502706
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The primary objective of this study is to determine the safety and tolerability of GS-0189
      (formerly FSI-189) as monotherapy and in combination with rituximab in participants with
      relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL).
The study will consist of 5 parts: 1) an initial Monotherapy Dose Escalation (MDE) part, 2) a
      Combination Dose Escalation (CDE) part, 3) a Pharmacokinetic (PK) Evaluation part, 4) an
      Alternate Schedule Evaluation (ASE) part and 5) a diffuse large B-cell lymphoma (DLBCL)
      Expansion part.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events
time frame: Up to 11 months
description: Adverse events as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0
measure: Percentage of Participants Experiencing Laboratory Abnormalities
time frame: Up to 11 months
measure: Pharmacokinetic (PK) Parameter: AUClast of GS-0189
time frame: Up to 11 months
description: AUClast is defined as the concentration of drug from time zero to the last observable concentration.
measure: PK Parameter: AUCtau of GS-0189
time frame: Up to 11 months
description: AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
measure: PK Parameter: Cmax of GS-0189
time frame: Up to 11 months
description: Cmax is defined as the maximum observed concentration of drug.
measure: PK Parameter: Accumulation Ratio (AR) of GS-0189
time frame: Up to 11 months
description: AR is defined as ratio based on Cmax and AUCtau after first dose and after multiple doses.
measure: PK Parameter: Tmax of GS-0189
time frame: Up to 11 months
description: Tmax is defined as the time (observed time point) of Cmax.
measure: PK Parameter: AUC0-tau/D Dose-normalized AUCtau of GS-0189
time frame: Up to 11 months
description: AUC0-tau/D is defined dose normalized area under the concentration-time curve from time zero (pre dose time point of the infusion) to the end of the dosing interval.
measure: Percentage of Signal Regulatory Protein Alpha (SIRPα) Receptor Occupancy in the Blood
time frame: Up to 11 months
measure: Serum Concentration of GS-0189
time frame: Up to 11 months
measure: Rate of Anti-GS-0189 Antibody Positivity
time frame: Up to 11 months
measure: Objective response rate (ORR)
time frame: Up to 2 years
description: ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) as assessed by Lugano Classification response criteria for lymphomas.
measure: Duration of Response (DOR)
time frame: Up to 2 years
description: DOR is defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of disease progression.
measure: Progression-free Survival (PFS)
time frame: Up to 2 years
description: PFS is defined as the interval from the first dose date of drug to the earlier of the first documentation of definitive disease progression or death from any cause.
measure: Overall Survival (OS)
time frame: Up to 2 years
description: OS is defined as the interval from the first dose date of drug to death from any cause.
measure: Time to Progression (TTP)
time frame: Up to 2 years
description: TTP is defined as the interval from the first dose date of drug to the earlier of the first documentation of definitive disease progression.
arm group label: GS-0189 (Monotherapy Dose Escalation, MDE)
arm group type: Experimental
description: Relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) participants will receive GS-0189 doses of 10, 30, or 100 mg every 2 weeks.
arm group label: GS-0189 + Rituximab (Combination Dose Escalation, CDE)
arm group type: Experimental
description: R/R NHL participants will receive GS-0189 doses of 100, 300, 1000, 2000, and 3000 mg in combination with rituximab at 375 mg/m^2.
arm group label: GS-0189 + Rituximab (Pharmacokinetic (PK) Evaluation)
arm group type: Experimental
description: R/R NHL participants will receive GS-0189 dose of up to 30 mg followed by the highest designated safe dose from the Combination Dose Escalation cohort (CDE) in combination with rituximab at 375 mg/m^2.
arm group label: GS-0189 + Rituximab (Alternate Schedule Evaluation, ASE)
arm group type: Experimental
description: R/R NHL participants will receive GS-0189 every 4 weeks in combination with rituximab 375 mg/m^2. The GS-0189 dose will be determined based on the totality of safety, PK, and pharmacodynamic (PD) data from the preceding cohorts.
arm group label: GS-0189 + Rituximab (DLBCL Expansion)
arm group type: Experimental
description: Diffuse large B-cell lymphoma (DLBCL) participants will receive GS-0189 in combination with rituximab 375 mg/m^2. The GS-0189 dose will be determined based on the totality of safety, PK, and PD data from the preceding cohorts.
intervention type: Drug
intervention name: GS-0189
description: GS-0189 will be administered intravenously.
arm group label: GS-0189 (Monotherapy Dose Escalation, MDE)
arm group label: GS-0189 + Rituximab (Alternate Schedule Evaluation, ASE)
arm group label: GS-0189 + Rituximab (Combination Dose Escalation, CDE)
arm group label: GS-0189 + Rituximab (DLBCL Expansion)
arm group label: GS-0189 + Rituximab (Pharmacokinetic (PK) Evaluation)
other name: FSI-189
intervention type: Drug
intervention name: Rituximab
description: Rituximab will be administered intravenously.
arm group label: GS-0189 + Rituximab (Alternate Schedule Evaluation, ASE)
arm group label: GS-0189 + Rituximab (Combination Dose Escalation, CDE)
arm group label: GS-0189 + Rituximab (DLBCL Expansion)
arm group label: GS-0189 + Rituximab (Pharmacokinetic (PK) Evaluation)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gilead Study Director
role: Study Director
affiliation: Gilead Sciences
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: https://www.gileadclinicaltrials.com/study/?id=SRP001
description: Gilead Clinical Trials Website
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Non-Hodgkin
mesh term: Rituximab
sharing ipd: No