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

NCT04502706 | Terminated Phase 1 FDA Drug

• 1 other identifier: SRP001
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 5

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).

Conditions

Non-hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (15)

• Percentage of Participants Experiencing Laboratory Abnormalities

  Up to 11 months

• Pharmacokinetic (PK) Parameter: AUClast of GS-0189

  Up to 11 months

• PK Parameter: AUCtau of GS-0189

  Up to 11 months

• PK Parameter: Cmax of GS-0189

  Up to 11 months

• PK Parameter: Accumulation Ratio (AR) of GS-0189

  Up to 11 months

Study Arms (5)

GS-0189 (Monotherapy Dose Escalation, MDE)

EXPERIMENTAL

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 + Rituximab (Combination Dose Escalation, CDE)

EXPERIMENTAL

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; Drug: Rituximab

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

EXPERIMENTAL

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; Drug: Rituximab

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

EXPERIMENTAL

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; Drug: Rituximab

GS-0189 + Rituximab (DLBCL Expansion)

EXPERIMENTAL

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; Drug: Rituximab

Interventions

GS-0189 DRUG

GS-0189 will be administered intravenously.

Also known as: FSI-189

GS-0189 (Monotherapy Dose Escalation, MDE); GS-0189 + Rituximab (Alternate Schedule Evaluation, ASE); GS-0189 + Rituximab (Combination Dose Escalation, CDE); GS-0189 + Rituximab (DLBCL Expansion); GS-0189 + Rituximab (Pharmacokinetic (PK) Evaluation)

Rituximab DRUG

Rituximab will be administered intravenously.

GS-0189 + Rituximab (Alternate Schedule Evaluation, ASE); GS-0189 + Rituximab (Combination Dose Escalation, CDE); GS-0189 + Rituximab (DLBCL Expansion); GS-0189 + Rituximab (Pharmacokinetic (PK) Evaluation)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (5)

University of Alabama Comprehensive Cancer Center

Birmingham, Alabama, 35233, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2020
• First Posted: August 6, 2020
• Study Start: November 17, 2020
• Primary Completion: March 31, 2022
• Study Completion: March 31, 2022
• Last Updated: June 5, 2023

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)