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