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
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 5
- 主要终点
- Percentage of Participants Experiencing Treatment-Emergent Adverse Events
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- •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.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
GS-0189 (Monotherapy Dose Escalation, MDE)
Relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) participants will receive GS-0189 doses of 10, 30, or 100 mg every 2 weeks.
干预措施: GS-0189 (Drug)
GS-0189 + Rituximab (Combination Dose Escalation, CDE)
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.
干预措施: GS-0189 (Drug)
GS-0189 + Rituximab (Combination Dose Escalation, CDE)
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.
干预措施: Rituximab (Drug)
GS-0189 + Rituximab (Pharmacokinetic (PK) Evaluation)
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.
干预措施: GS-0189 (Drug)
GS-0189 + Rituximab (Pharmacokinetic (PK) Evaluation)
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.
干预措施: Rituximab (Drug)
GS-0189 + Rituximab (Alternate Schedule Evaluation, ASE)
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.
干预措施: GS-0189 (Drug)
GS-0189 + Rituximab (Alternate Schedule Evaluation, ASE)
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.
干预措施: Rituximab (Drug)
GS-0189 + Rituximab (DLBCL Expansion)
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.
干预措施: GS-0189 (Drug)
GS-0189 + Rituximab (DLBCL Expansion)
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.
干预措施: Rituximab (Drug)
结局指标
主要结局
Percentage of Participants Experiencing Treatment-Emergent Adverse Events
时间窗: Up to 11 months
Adverse events as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0
次要结局
- Pharmacokinetic (PK) Parameter: AUClast of GS-0189(Up to 11 months)
- Percentage of Participants Experiencing Laboratory Abnormalities(Up to 11 months)
- PK Parameter: AUCtau of GS-0189(Up to 11 months)
- PK Parameter: Tmax of GS-0189(Up to 11 months)
- Rate of Anti-GS-0189 Antibody Positivity(Up to 11 months)
- PK Parameter: Cmax of GS-0189(Up to 11 months)
- PK Parameter: Accumulation Ratio (AR) of GS-0189(Up to 11 months)
- PK Parameter: AUC0-tau/D Dose-normalized AUCtau of GS-0189(Up to 11 months)
- Percentage of Signal Regulatory Protein Alpha (SIRPα) Receptor Occupancy in the Blood(Up to 11 months)
- Serum Concentration of GS-0189(Up to 11 months)
- Objective response rate (ORR)(Up to 2 years)
- Progression-free Survival (PFS)(Up to 2 years)
- Overall Survival (OS)(Up to 2 years)
- Duration of Response (DOR)(Up to 2 years)
- Time to Progression (TTP)(Up to 2 years)