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).
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).
Recruiting
Phase 1
Drug | Synonyms | Arms |
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GS-0189 | FSI-189 | GS-0189 (Monotherapy Dose Escalation, MDE) |
Rituximab | GS-0189 + Rituximab (Alternate Schedule Evaluation, ASE) |
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.
Name | Type | Description | Interventions |
---|---|---|---|
GS-0189 (Monotherapy Dose Escalation, MDE) | Experimental | Relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) participants will receive GS-0189 doses of 10, 30, or 100 mg every 2 weeks. |
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GS-0189 + Rituximab (Combination Dose Escalation, CDE) | Experimental | R/R NHL participants will receive GS-0189 doses of 100, 200, 400, or 800 mg in combination with rituximab at 375 mg/m^2. |
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GS-0189 + Rituximab (Pharmacokinetic (PK) Evaluation) | Experimental | R/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. |
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GS-0189 + Rituximab (Alternate Schedule Evaluation, ASE) | Experimental | 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. |
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GS-0189 + Rituximab (DLBCL Expansion) | Experimental | 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. |
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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 |
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 |
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. |
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Gilead Sciences |
July 20, 2021