Clinical trial NCT04502706: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Non-hodgkin Lymphoma
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2020-08-06
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events
timeFrame: Up to 11 months
Secondary outcomes:
measure: Percentage of Participants Experiencing Laboratory Abnormalities
timeFrame: Up to 11 months
measure: Pharmacokinetic (PK) Parameter: AUClast of GS-0189
timeFrame: Up to 11 months
measure: PK Parameter: AUCtau of GS-0189
timeFrame: Up to 11 months
measure: PK Parameter: Cmax of GS-0189
timeFrame: Up to 11 months
measure: PK Parameter: Accumulation Ratio (AR) of GS-0189
timeFrame: Up to 11 months
measure: PK Parameter: Tmax of GS-0189
timeFrame: Up to 11 months
measure: PK Parameter: AUC0-tau/D Dose-normalized AUCtau of GS-0189
timeFrame: Up to 11 months
measure: Percentage of Signal Regulatory Protein Alpha (SIRPα) Receptor Occupancy in the Blood
timeFrame: Up to 11 months
measure: Serum Concentration of GS-0189
timeFrame: Up to 11 months
measure: Rate of Anti-GS-0189 Antibody Positivity
timeFrame: Up to 11 months
measure: Objective response rate (ORR)
timeFrame: Up to 2 years
measure: Duration of Response (DOR)
timeFrame: Up to 2 years
measure: Progression-free Survival (PFS)
timeFrame: Up to 2 years
measure: Overall Survival (OS)
timeFrame: Up to 2 years
measure: Time to Progression (TTP)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Comprehensive Cancer Center
state: Alabama
city: Duarte
country: United States
facility: City of Hope
state: California
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: