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 Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04502706
• Other study ID #: SRP001
• Status: Terminated
• Phase: Phase 1
• Start date: November 17, 2020
• Est. completion date: March 31, 2022

Study information

• Verified date: May 2022
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: March 31, 2022
• Est. primary completion date: March 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (SIRPa)-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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin
• Non-hodgkin Lymphoma

Intervention

Drug:
• GS-0189
GS-0189 will be administered intravenously.
• Rituximab
Rituximab will be administered intravenously.

Locations

Country	Name	City	State
United States	University of Alabama Comprehensive Cancer Center	Birmingham	Alabama
United States	City of Hope	Duarte	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Florida Cancer Specialists	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Experiencing Treatment-Emergent Adverse Events	Adverse events as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0	Up to 11 months
Secondary	Percentage of Participants Experiencing Laboratory Abnormalities		Up to 11 months
Secondary	Pharmacokinetic (PK) Parameter: AUClast of GS-0189	AUClast is defined as the concentration of drug from time zero to the last observable concentration.	Up to 11 months
Secondary	PK Parameter: AUCtau of GS-0189	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).	Up to 11 months
Secondary	PK Parameter: Cmax of GS-0189	Cmax is defined as the maximum observed concentration of drug.	Up to 11 months
Secondary	PK Parameter: Accumulation Ratio (AR) of GS-0189	AR is defined as ratio based on Cmax and AUCtau after first dose and after multiple doses.	Up to 11 months
Secondary	PK Parameter: Tmax of GS-0189	Tmax is defined as the time (observed time point) of Cmax.	Up to 11 months
Secondary	PK Parameter: AUC0-tau/D Dose-normalized AUCtau of GS-0189	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.	Up to 11 months
Secondary	Percentage of Signal Regulatory Protein Alpha (SIRPa) Receptor Occupancy in the Blood		Up to 11 months
Secondary	Serum Concentration of GS-0189		Up to 11 months
Secondary	Rate of Anti-GS-0189 Antibody Positivity		Up to 11 months
Secondary	Objective response rate (ORR)	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.	Up to 2 years
Secondary	Duration of Response (DOR)	DOR is defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of disease progression.	Up to 2 years
Secondary	Progression-free Survival (PFS)	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.	Up to 2 years
Secondary	Overall Survival (OS)	OS is defined as the interval from the first dose date of drug to death from any cause.	Up to 2 years
Secondary	Time to Progression (TTP)	TTP is defined as the interval from the first dose date of drug to the earlier of the first documentation of definitive disease progression.	Up to 2 years

External Links

•   Gilead Clinical Trials Website