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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04502706
Recruitment Status : Terminated (Sponsor's decision to discontinue development of this molecule)
First Posted : August 6, 2020
Last Update Posted : May 20, 2022
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

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).

Condition or disease Intervention/treatment Phase
Non-hodgkin Lymphoma Drug: GS-0189 Drug: Rituximab Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 17, 2020
Actual Primary Completion Date : March 31, 2022
Actual Study Completion Date : March 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Rituximab

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 Name: 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 Name: 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 Name: 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 Name: 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 Name: FSI-189

Drug: Rituximab
Rituximab will be administered intravenously.




Primary Outcome Measures :
  1. Percentage of Participants Experiencing Treatment-Emergent Adverse Events [ Time Frame: Up to 11 months ]
    Adverse events as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0


Secondary Outcome Measures :
  1. Percentage of Participants Experiencing Laboratory Abnormalities [ Time Frame: Up to 11 months ]
  2. Pharmacokinetic (PK) Parameter: AUClast of GS-0189 [ Time Frame: Up to 11 months ]
    AUClast is defined as the concentration of drug from time zero to the last observable concentration.

  3. PK Parameter: AUCtau of GS-0189 [ Time Frame: Up to 11 months ]
    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

  4. PK Parameter: Cmax of GS-0189 [ Time Frame: Up to 11 months ]
    Cmax is defined as the maximum observed concentration of drug.

  5. PK Parameter: Accumulation Ratio (AR) of GS-0189 [ Time Frame: Up to 11 months ]
    AR is defined as ratio based on Cmax and AUCtau after first dose and after multiple doses.

  6. PK Parameter: Tmax of GS-0189 [ Time Frame: Up to 11 months ]
    Tmax is defined as the time (observed time point) of Cmax.

  7. PK Parameter: AUC0-tau/D Dose-normalized AUCtau of GS-0189 [ Time Frame: Up to 11 months ]
    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.

  8. Percentage of Signal Regulatory Protein Alpha (SIRPα) Receptor Occupancy in the Blood [ Time Frame: Up to 11 months ]
  9. Serum Concentration of GS-0189 [ Time Frame: Up to 11 months ]
  10. Rate of Anti-GS-0189 Antibody Positivity [ Time Frame: Up to 11 months ]
  11. Objective response rate (ORR) [ Time Frame: Up to 2 years ]
    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.

  12. Duration of Response (DOR) [ Time Frame: Up to 2 years ]
    DOR is defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of disease progression.

  13. Progression-free Survival (PFS) [ Time Frame: Up to 2 years ]
    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.

  14. Overall Survival (OS) [ Time Frame: Up to 2 years ]
    OS is defined as the interval from the first dose date of drug to death from any cause.

  15. Time to Progression (TTP) [ Time Frame: Up to 2 years ]
    TTP is defined as the interval from the first dose date of drug to the earlier of the first documentation of definitive disease progression.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04502706


Locations
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United States, Alabama
University of Alabama Comprehensive Cancer Center
Birmingham, Alabama, United States, 35233
United States, California
City of Hope
Duarte, California, United States, 91010
United States, Florida
Florida Cancer Specialists
Sarasota, Florida, United States, 34232
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
Additional Information:
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT04502706    
Other Study ID Numbers: SRP001
First Posted: August 6, 2020    Key Record Dates
Last Update Posted: May 20, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents