Clinical Trials /

Study of 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 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:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of FSI-189 as Monotherapy and in Combination With Rituximab in Participants With Relapsed/Refractory Non-Hodgkin Lymphoma
  • Official Title: A Phase 1 Study of 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
FSI-189FSI-189 (Monotherapy Dose Escalation)
RituximabFSI-189 + Rituximab (Combination Dose Escalation)

Purpose

The primary objective of this study is to determine the safety and tolerability of 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 4 parts: 1) an initial Monotherapy Dose Escalation part, 2) a
      Combination Dose Escalation part, 3) a Pharmacokinetic (PK) Evaluation part, and 4) a diffuse
      large B-cell lymphoma (DLBCL) Expansion part.
    

Trial Arms

NameTypeDescriptionInterventions
FSI-189 (Monotherapy Dose Escalation)ExperimentalParticipants will receive FSI-189 doses of 10, 30, or 100 mg every 2 weeks for 9 months.
  • FSI-189
FSI-189 + Rituximab (Combination Dose Escalation)ExperimentalParticipants will receive FSI-189 doses of 100, 200, 400, or 800 mg every 2 weeks in combination with rituximab at 375 mg/m^2 for 9 months.
  • FSI-189
  • Rituximab
FSI-189 + Rituximab (Pharmacokinetic (PK) Evaluation)ExperimentalParticipants will either receive FSI-189 3 mg at Cycle 1 Day 1, followed by FSI-189 100 mg from Cycle 1 Day 15 onward every 2 weeks or FSI-189 10 mg at Cycle 1 Day 1, followed by FSI-189 200 mg from Cycle 1 Day 15 onward every 2 weeks in combination with rituximab at 375 mg/m^2 for 9 months
  • FSI-189
  • Rituximab
FSI-189 + Rituximab (DLBCL Expansion)ExperimentalDiffuse large B-cell lymphoma (DLBCL) participants will receive FSI-189 and rituximab with the recommended dose and schedule based on the Monotherapy Dose Escalation, Combination Dose Escalation, and PK Evaluation data.
  • FSI-189
  • Rituximab

Eligibility Criteria

        Key Inclusion Criteria:

          -  B-cell non-Hodgkin's lymphoma (NHL) expressing CD20 by immunohistochemistry (IHC) or
             flow cytometry, relapsed/refractory (R/R) to at least 2 prior lines of therapy,
             including individuals with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma
             (FL), and marginal zone lymphomas (MZL). Prior autologous hematopoietic cell
             transplantation and individuals with transformed lymphomas are permitted. 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.

          -  Disease that is measurable or assessable for response per Lugano criteria for
             lymphomas

          -  Laboratory measurements, blood counts:

               -  a. Absolute neutrophil count ≥ 1.0 × 10^9/mL.

               -  b. Platelets ≥ 75 × 10^9/mL.

          -  Laboratory measurements, hepatic function:

               -  a. aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ≤ 2.5 × upper
                  limit of normal (ULN).

               -  b. Bilirubin ≤ 1.5 × or 3.0 × ULN and primarily unconjugated if individual has a
                  documented history of Gilbert's syndrome or a genetic equivalent.

          -  Laboratory measurements, renal function: Serum creatinine ≤ 1.5 × ULN or calculated
             glomerular filtration rate > 40 mL/min/1.73 m^2 using the Cockcroft-Gault formula.

        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.

          -  Prior anticancer therapy including chemotherapy, hormonal therapy, and investigational
             agents within the last 4 weeks.

          -  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.

        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:First dose date up 9 months plus 30 days
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:First dose date up 9 months plus 30 days
Safety Issue:
Description:The percentage of participants experiencing any clinically significant laboratory abnormality will be summarized.
Measure:Pharmacokinetic (PK) Parameter: AUClast of FSI-189
Time Frame:Days 1, 2, 8, 15, and 22 pre-infusion and within 1 hour post-infusion (Cycles 1-2); Day 1 pre-infusion (Cycles 3-5, 6, 8, 10, 13 and Safety Follow-up Visit); infusion duration: 60 mins; each cycle = 28 days
Safety Issue:
Description:AUClast is defined as the concentration of drug from time zero to the last observable concentration. For the monotherapy dose escalation (MDE), combination dose escalation (CDE), and PK evaluation (PKE) cohorts: On Cycle 1 Day 1, an additional 6 hour post-infusion sample will be taken. For the diffuse large B-cell lymphoma (DLBCL) expansion cohort: Samples will not be taken on Cycle 1 Day 2 and Cycle 2 Days 2, 8, and 22. On Cycle 1 Day 8, sample will only be taken pre-infusion. Safety Follow-up Visit will occur within 30 days after the last dose.
Measure:PK Parameter: AUCtau of FSI-189
Time Frame:Days 1, 2, 8, 15, and 22 pre-infusion and within 1 hour post-infusion (Cycles 1-2); Day 1 pre-infusion (Cycles 3-5, 6, 8, 10, 13 and Safety Follow-up Visit); infusion duration: 60 mins; each cycle = 28 days
Safety Issue:
Description:AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). For the MDE, CDE, and PKE cohorts: On Cycle 1 Day 1, an additional 6 hour post-infusion sample will be taken. For the DLBCL expansion cohort: Samples will not be taken on Cycle 1 Day 2 and Cycle 2 Days 2, 8, and 22. On Cycle 1 Day 8, sample will only be taken pre-infusion. Safety Follow-up Visit will occur within 30 days after the last dose.
Measure:PK Parameter: Cmax of FSI-189
Time Frame:Days 1, 2, 8, 15, and 22 pre-infusion and within 1 hour post-infusion (Cycles 1-2); Day 1 pre-infusion (Cycles 3-5, 6, 8, 10, 13 and Safety Follow-up Visit); infusion duration: 60 mins; each cycle = 28 days
Safety Issue:
Description:Cmax is defined as the maximum observed concentration of drug. For the MDE, CDE, and PKE cohorts: On Cycle 1 Day 1, an additional 6 hour post-infusion sample will be taken. For the DLBCL expansion cohort: Samples will not be taken on Cycle 1 Day 2 and Cycle 2 Days 2, 8, and 22. On Cycle 1 Day 8, sample will only be taken pre-infusion. Safety Follow-up Visit will occur within 30 days after the last dose.
Measure:PK Parameter: Accumulation Ratio (AR) of FSI-189
Time Frame:Days 1, 2, 8, 15, and 22 pre-infusion and within 1 hour post-infusion (Cycles 1-2); Day 1 pre-infusion (Cycles 3-5, 6, 8, 10, 13 and Safety Follow-up Visit); infusion duration: 60 mins; each cycle = 28 days
Safety Issue:
Description:AR is defined as ratio based on Cmax and AUCtau after first dose and after multiple doses. For the MDE, CDE, and PKE cohorts: On Cycle 1 Day 1, an additional 6 hour post-infusion sample will be taken. For the DLBCL expansion cohort: Samples will not be taken on Cycle 1 Day 2 and Cycle 2 Days 2, 8, and 22. On Cycle 1 Day 8, sample will only be taken pre-infusion. Safety Follow-up Visit will occur within 30 days after the last dose.
Measure:PK Parameter: Tmax of FSI-189
Time Frame:Days 1, 2, 8, 15, and 22 pre-infusion and within 1 hour post-infusion (Cycles 1-2); Day 1 pre-infusion (Cycles 3-5, 6, 8, 10, 13 and Safety Follow-up Visit); infusion duration: 60 mins; each cycle = 28 days
Safety Issue:
Description:Tmax is defined as the time (observed time point) of Cmax. For the MDE, CDE, and PKE cohorts: On Cycle 1 Day 1, an additional 6 hour post-infusion sample will be taken. For the DLBCL expansion cohort: Samples will not be taken on Cycle 1 Day 2 and Cycle 2 Days 2, 8, and 22. On Cycle 1 Day 8, sample will only be taken pre-infusion. Safety Follow-up Visit will occur within 30 days after the last dose.
Measure:PK Parameter: AUC0-tau/D Dose-normalized AUCtau of FSI-189
Time Frame:Days 1, 2, 8, 15, and 22 pre-infusion and within 1 hour post-infusion (Cycles 1-2); Day 1 pre-infusion (Cycles 3-5, 6, 8, 10, 13 and Safety Follow-up Visit); infusion duration: 60 mins; each cycle = 28 days
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. For the MDE, CDE, and PKE cohorts: On Cycle 1 Day 1, an additional 6 hour post-infusion sample will be taken. For the DLBCL expansion cohort: Samples will not be taken on Cycle 1 Day 2 and Cycle 2 Days 2, 8, and 22. On Cycle 1 Day 8, sample will only be taken pre-infusion. Safety Follow-up Visit will occur within 30 days after the last dose.
Measure:Percentage of Signal Regulatory Protein Alpha (SIRPα) Receptor Occupancy in the Blood
Time Frame:Days 1, 8, 15, and 22 pre-infusion (Cycle 1); Days 1 and 15 pre-infusion (Cycle 2); Day 1 pre-infusion (Cycles 3-5, 6, 8, 10, 13 and Safety Follow-up Visit); infusion duration: 60 mins; each cycle = 28 days
Safety Issue:
Description:For the MDE, CDE, and PKE cohorts: On Days 1 and 15 Cycle 1 & Cycle 2 an additional 1 hour post-infusion sample will be taken. Safety Follow-up Visit will occur within 30 days after the last dose.
Measure:Serum Concentration of FSI-189
Time Frame:Days 1, 2, 8, 15, & 22 (Cycle 1); Day 1 (Cycles 2-13, and Safety Follow-up Visit): 72 hours before study drug administration prior to first dose of FSI-189 and 24 hours before study drug administration with subsequent FSI-189 doses; each cycle = 28 days
Safety Issue:
Description:Safety Follow-up Visit will occur within 30 days after the last dose.
Measure:Rate of Anti-FSI-189 Antibody Positivity
Time Frame:Days 1 and 15 (Cycles 1-2); Day 1 (Cycles 3-5, 6, 8, 10, 13, and Safety Follow-up Visit): pre-infusion; infusion duration: 60 mins; each cycle = 28 days
Safety Issue:
Description:Safety Follow-up Visit will occur within 30 days after the last dose.
Measure:Objective response rate (ORR)
Time Frame:Up to 9 months
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 9 months
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 9 months
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 9 months
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:Not yet recruiting
Lead Sponsor:Gilead Sciences

Last Updated

August 4, 2020