Back to resultsStudy of GS-0189 (Formerly FSI-189) as Monotherapy and in Combination With Rituximab in Participants With Relapsed/Refractory Non-Hodgkin Lymphoma
Primary Purpose
Non-hodgkin Lymphoma
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
GS-0189
Rituximab
Sponsored by
About this trial
This is an interventional treatment trial for Non-hodgkin Lymphoma
Eligibility Criteria
Key Inclusion Criteria:
- DLBCL, follicular lymphoma (FL), mantle cell lymphoma (MCL), or marginal zone lymphoma (MZL) 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: DLBCL 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 ≤ 90 days from first dose of study drug.
- 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.
- Rituximab-containing cohorts only: Receipt of live/attenuated vaccines within 30 days of rituximab dosing
- Has persisting toxicity related to prior therapy of Grade > 1 in severity per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Sites / Locations
- University of Alabama Comprehensive Cancer Center
- City of Hope
- Florida Cancer Specialists
- Washington University School of Medicine
- University of Oklahoma Health Sciences Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
GS-0189 (Monotherapy Dose Escalation, MDE)
GS-0189 + Rituximab (Combination Dose Escalation, CDE)
GS-0189 + Rituximab (Pharmacokinetic (PK) Evaluation)
GS-0189 + Rituximab (Alternate Schedule Evaluation, ASE)
GS-0189 + Rituximab (DLBCL Expansion)
Arm Description
Relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) participants will receive GS-0189 doses of 10, 30, or 100 mg every 2 weeks.
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Adverse events as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0
Secondary Outcome Measures
Percentage of Participants Experiencing Laboratory Abnormalities
Pharmacokinetic (PK) Parameter: AUClast of GS-0189
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
PK Parameter: AUCtau of GS-0189
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
PK Parameter: Cmax of GS-0189
Cmax is defined as the maximum observed concentration of drug.
PK Parameter: Accumulation Ratio (AR) of GS-0189
AR is defined as ratio based on Cmax and AUCtau after first dose and after multiple doses.
PK Parameter: Tmax of GS-0189
Tmax is defined as the time (observed time point) of Cmax.
PK Parameter: AUC0-tau/D Dose-normalized AUCtau of GS-0189
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.
Percentage of Signal Regulatory Protein Alpha (SIRPα) Receptor Occupancy in the Blood
Serum Concentration of GS-0189
Rate of Anti-GS-0189 Antibody Positivity
Objective response rate (ORR)
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.
Duration of Response (DOR)
DOR is defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of disease progression.
Progression-free Survival (PFS)
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.
Overall Survival (OS)
OS is defined as the interval from the first dose date of drug to death from any cause.
Time to Progression (TTP)
TTP is defined as the interval from the first dose date of drug to the earlier of the first documentation of definitive disease progression.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04502706
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Terminated
Why Stopped
Sponsor's decision to discontinue development of this molecule
Study Start Date
November 17, 2020 (Actual)
Primary Completion Date
March 31, 2022 (Actual)
Study Completion Date
March 31, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-hodgkin Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GS-0189 (Monotherapy Dose Escalation, MDE)
Arm Type
Experimental
Arm 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 Title
GS-0189 + Rituximab (Combination Dose Escalation, CDE)
Arm Type
Experimental
Arm 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 Title
GS-0189 + Rituximab (Pharmacokinetic (PK) Evaluation)
Arm Type
Experimental
Arm 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 Title
GS-0189 + Rituximab (Alternate Schedule Evaluation, ASE)
Arm Type
Experimental
Arm 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 Title
GS-0189 + Rituximab (DLBCL Expansion)
Arm Type
Experimental
Arm 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(s)
GS-0189
Other Intervention Name(s)
FSI-189
Intervention Description
GS-0189 will be administered intravenously.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
Rituximab will be administered intravenously.
Primary Outcome Measure Information:
Title
Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Description
Adverse events as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0
Time Frame
Up to 11 months
Secondary Outcome Measure Information:
Title
Percentage of Participants Experiencing Laboratory Abnormalities
Time Frame
Up to 11 months
Title
Pharmacokinetic (PK) Parameter: AUClast of GS-0189
Description
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Time Frame
Up to 11 months
Title
PK Parameter: AUCtau of GS-0189
Description
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Time Frame
Up to 11 months
Title
PK Parameter: Cmax of GS-0189
Description
Cmax is defined as the maximum observed concentration of drug.
Time Frame
Up to 11 months
Title
PK Parameter: Accumulation Ratio (AR) of GS-0189
Description
AR is defined as ratio based on Cmax and AUCtau after first dose and after multiple doses.
Time Frame
Up to 11 months
Title
PK Parameter: Tmax of GS-0189
Description
Tmax is defined as the time (observed time point) of Cmax.
Time Frame
Up to 11 months
Title
PK Parameter: AUC0-tau/D Dose-normalized AUCtau of GS-0189
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.
Time Frame
Up to 11 months
Title
Percentage of Signal Regulatory Protein Alpha (SIRPα) Receptor Occupancy in the Blood
Time Frame
Up to 11 months
Title
Serum Concentration of GS-0189
Time Frame
Up to 11 months
Title
Rate of Anti-GS-0189 Antibody Positivity
Time Frame
Up to 11 months
Title
Objective response rate (ORR)
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.
Time Frame
Up to 2 years
Title
Duration of Response (DOR)
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.
Time Frame
Up to 2 years
Title
Progression-free Survival (PFS)
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.
Time Frame
Up to 2 years
Title
Overall Survival (OS)
Description
OS is defined as the interval from the first dose date of drug to death from any cause.
Time Frame
Up to 2 years
Title
Time to Progression (TTP)
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.
Time Frame
Up to 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
DLBCL, follicular lymphoma (FL), mantle cell lymphoma (MCL), or marginal zone lymphoma (MZL) 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: DLBCL 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 ≤ 90 days from first dose of study drug.
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.
Rituximab-containing cohorts only: Receipt of live/attenuated vaccines within 30 days of rituximab dosing
Has persisting toxicity related to prior therapy of Grade > 1 in severity per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama Comprehensive Cancer Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Florida Cancer Specialists
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34232
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://www.gileadclinicaltrials.com/study/?id=SRP001
Description
Gilead Clinical Trials Website
Learn more about this trial
Study of GS-0189 (Formerly FSI-189) as Monotherapy and in Combination With Rituximab in Participants With Relapsed/Refractory Non-Hodgkin Lymphoma
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