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

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

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).

Study Overview

• Status: Terminated
• Conditions: Non-hodgkin Lymphoma
• Intervention / Treatment: Drug: GS-0189; Drug: Rituximab

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama Comprehensive Cancer Center
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • Florida
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: GS-0189; GS-0189 will be administered intravenously.; Other Names: FSI-189
Experimental: 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.	Drug: GS-0189; GS-0189 will be administered intravenously.; Other Names: FSI-189; Drug: Rituximab; Rituximab will be administered intravenously.
Experimental: 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.	Drug: GS-0189; GS-0189 will be administered intravenously.; Other Names: FSI-189; Drug: Rituximab; Rituximab will be administered intravenously.
Experimental: 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.	Drug: GS-0189; GS-0189 will be administered intravenously.; Other Names: FSI-189; Drug: Rituximab; Rituximab will be administered intravenously.
Experimental: 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.	Drug: GS-0189; GS-0189 will be administered intravenously.; Other Names: FSI-189; Drug: Rituximab; Rituximab will be administered intravenously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Experiencing Laboratory Abnormalities		Up to 11 months
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
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
PK Parameter: Cmax of GS-0189	Cmax is defined as the maximum observed concentration of drug.	Up to 11 months
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
PK Parameter: Tmax of GS-0189	Tmax is defined as the time (observed time point) of Cmax.	Up to 11 months
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
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
Rate of Anti-GS-0189 Antibody Positivity		Up to 11 months
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2020
• Primary Completion (Actual): March 31, 2022
• Study Completion (Actual): March 31, 2022

Study Registration Dates

• First Submitted: July 16, 2020
• First Submitted That Met QC Criteria: August 4, 2020
• First Posted (Actual): August 6, 2020

Study Record Updates

• Last Update Posted (Actual): June 5, 2023
• Last Update Submitted That Met QC Criteria: June 1, 2023
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: SRP001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No