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

Gilead Sciences

Status and phase: Terminated; Phase 1

Conditions: Non-hodgkin Lymphoma

Treatments: Drug: GS-0189; Drug: Rituximab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04502706

SRP001

Details and patient eligibility

About

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).

Full 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.

Enrollment: 9 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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9 participants in 5 patient groups

GS-0189 (Monotherapy Dose Escalation, MDE)

Experimental group

Description:

Relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) participants will receive GS-0189 doses of 10, 30, or 100 mg every 2 weeks.

Treatment:

Drug: GS-0189

GS-0189 + Rituximab (Combination Dose Escalation, CDE)

Experimental group

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.

Treatment:

Drug: Rituximab

Drug: GS-0189

GS-0189 + Rituximab (Pharmacokinetic (PK) Evaluation)

Experimental group

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.

Treatment:

Drug: Rituximab

Drug: GS-0189

GS-0189 + Rituximab (Alternate Schedule Evaluation, ASE)

Experimental group

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.

Treatment:

Drug: Rituximab

Drug: GS-0189

GS-0189 + Rituximab (DLBCL Expansion)

Experimental group

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.

Treatment:

Drug: Rituximab

Drug: GS-0189