Non-hodgkin Lymphoma
Conditions
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.
Interventions
DRUGGS-0189
GS-0189 will be administered intravenously.
DRUGRituximab
Rituximab will be administered intravenously.
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events | Up to 11 months | Adverse events as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) Parameter: AUClast of GS-0189 | Up to 11 months | AUClast is defined as the concentration of drug from time zero to the last observable concentration. |
| PK Parameter: AUCtau of GS-0189 | 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). |
| PK Parameter: Cmax of GS-0189 | Up to 11 months | Cmax is defined as the maximum observed concentration of drug. |
| PK Parameter: Accumulation Ratio (AR) of GS-0189 | Up to 11 months | AR is defined as ratio based on Cmax and AUCtau after first dose and after multiple doses. |
| PK Parameter: Tmax of GS-0189 | Up to 11 months | Tmax is defined as the time (observed time point) of Cmax. |
| PK Parameter: AUC0-tau/D Dose-normalized AUCtau of GS-0189 | 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. |
| Percentage of Signal Regulatory Protein Alpha (SIRPα) Receptor Occupancy in the Blood | Up to 11 months | — |
| Percentage of Participants Experiencing Laboratory Abnormalities | Up to 11 months | — |
| Rate of Anti-GS-0189 Antibody Positivity | Up to 11 months | — |
| Objective response rate (ORR) | 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. |
| Duration of Response (DOR) | 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. |
| Progression-free Survival (PFS) | 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. |
| Overall Survival (OS) | Up to 2 years | OS is defined as the interval from the first dose date of drug to death from any cause. |
| Time to Progression (TTP) | 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. |
| Serum Concentration of GS-0189 | Up to 11 months | — |
Countries
United States
Outcome results
None listed