Clinical Trials /

Study of GS-0189 (Formerly FSI-189) as Monotherapy and in Combination With Rituximab in Participants With Relapsed/Refractory Non-Hodgkin Lymphoma

NCT04502706

Description:

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).

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • Indolent Non-Hodgkin Lymphoma
  • Marginal Zone Lymphoma
  • Transformed Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of GS-0189 (Formerly FSI-189) as Monotherapy and in Combination With Rituximab in Participants With Relapsed/Refractory Non-Hodgkin Lymphoma
  • 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

Clinical Trial IDs

  • ORG STUDY ID: SRP001
  • NCT ID: NCT04502706

Conditions

  • Non-hodgkin Lymphoma

Interventions

DrugSynonymsArms
GS-0189FSI-189GS-0189 (Monotherapy Dose Escalation, MDE)
RituximabGS-0189 + Rituximab (Alternate Schedule Evaluation, ASE)

Purpose

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).

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
GS-0189 (Monotherapy Dose Escalation, MDE)ExperimentalRelapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) participants will receive GS-0189 doses of 10, 30, or 100 mg every 2 weeks.
  • GS-0189
GS-0189 + Rituximab (Combination Dose Escalation, CDE)ExperimentalR/R NHL participants will receive GS-0189 doses of 100, 200, 400, or 800 mg in combination with rituximab at 375 mg/m^2.
  • GS-0189
  • Rituximab
GS-0189 + Rituximab (Pharmacokinetic (PK) Evaluation)ExperimentalR/R NHL participants will receive GS-0189 dose of up to 30 mg followed by 100mg or 200mg in combination with rituximab at 375 mg/m^2.
  • GS-0189
  • Rituximab
GS-0189 + Rituximab (Alternate Schedule Evaluation, ASE)ExperimentalR/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.
  • GS-0189
  • Rituximab
GS-0189 + Rituximab (DLBCL Expansion)ExperimentalDiffuse 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.
  • GS-0189
  • Rituximab

Eligibility Criteria

        Key Inclusion Criteria:

          -  DLBCL, follicular lymphoma (FL), or marginal zone lymphoma (MZL) expressing CD20 by
             immunohistochemistry (IHC) or flow cytometry, relapsed/refractory (R/R) to at least 2
             prior lines of therapy. Prior autologous hematopoietic cell transplantation and
             individuals with transformed lymphomas are permitted. Individuals must be at least 3
             months out from prior autologous hematopoietic cell transplantation. Individuals with
             indolent lymphomas must be candidates for systemic treatment in the judgment of the
             treating physician.

          -  In the DLBCL Expansion part: Individuals must have de novo or transformed DLBCL
             expressing CD20 by IHC or flow cytometry, that is relapsed or refractory to at least 2
             prior lines of therapy. Prior autologous hematopoietic cell transplantation and
             individuals with transformed lymphomas are permitted.

          -  Eastern Cooperative Oncology Group (ECOG) score of 0 to 2.

          -  For the DLBCL expansion cohort, disease must be measurable for response per Lugano
             criteria. For all other cohorts, disease must be measurable or assessable for response
             per Lugano criteria.

          -  Exhibit acceptable hematopoietic, liver, renal, and coagulation function as assessed
             by laboratory tests.

        Key Exclusion Criteria:

          -  Individuals with active brain metastases (Individuals with stable treated central
             nervous system (CNS) lesions who are off corticosteroid therapy for at least 3 weeks
             are not considered active.

          -  Individuals with Burkitt's lymphoma.

          -  Prior treatment with a chimeric antigen receptor (CAR) T-cell therapy.

          -  Prior allogeneic stem cell transplant.

          -  Previous anticancer therapy including chemotherapy, hormonal therapy, and
             investigational agents within 3 weeks or at least 4 half-lives (up to a maximum of 4
             weeks), whichever is longer, prior to first dose of study drug.

          -  Known active or chronic hepatitis B or C infection or human immunodeficiency virus.

          -  Prior treatment with CD47 or signal regulatory protein alpha (SIRPα)-targeting agents.

          -  Hypersensitivity to the active substance, to murine proteins, or to any of the other
             excipients of rituximab

          -  Significant medical diseases or conditions, as assessed by the Investigator and
             Sponsor, that would substantially increase the risk:benefit ratio of participating in
             the study. This includes, but is not limited to, acute myocardial infarction within
             the last 6 months, unstable angina, uncontrolled diabetes mellitus, significant active
             infections, severely immunocompromised state, and congestive heart failure New York
             Heart Association Classes II to IV.

          -  Rituximab-containing cohorts only: Receipt of live/attenuated vaccines within 30 days
             of rituximab dosing

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Time Frame:Up to 11 months
Safety Issue:
Description:Adverse events as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0

Secondary Outcome Measures

Measure:Percentage of Participants Experiencing Laboratory Abnormalities
Time Frame:Up to 11 months
Safety Issue:
Description:
Measure:Pharmacokinetic (PK) Parameter: AUClast of GS-0189
Time Frame:Up to 11 months
Safety Issue:
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
Safety Issue:
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
Safety Issue:
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
Safety Issue:
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
Safety Issue:
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
Safety Issue:
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
Safety Issue:
Description:
Measure:Serum Concentration of GS-0189
Time Frame:Up to 11 months
Safety Issue:
Description:
Measure:Rate of Anti-GS-0189 Antibody Positivity
Time Frame:Up to 11 months
Safety Issue:
Description:
Measure:Objective response rate (ORR)
Time Frame:Up to 2 years
Safety Issue:
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
Safety Issue:
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
Safety Issue:
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
Safety Issue:
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
Safety Issue:
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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Gilead Sciences

Last Updated

June 30, 2021