A Phase 1b Study Evaluating GS-9820 in Subjects With Lymphoid Malignancies

Study Overview
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Brief Summary
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This study is to determine the appropriate dosing regimen of GS-9820 in subjects with lymphoid malignancies. This is a Phase 1b, open-label, dose-escalation and expansion study evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of GS-9820.

Official Title
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A Phase 1b Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of GS-9820 in Subjects With Lymphoid Malignancies

Conditions
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Lymphoid Malignancies

Intervention / Treatment
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* Drug: GS-9820


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously treated recurrent B-cell iNHL, DLBCL, MCL, HL or CLL Measurable lymphadenopathy Requires therapy Exclusion Criteria: Recent history of a major non-lymphoid malignancy Evidence of ongoing infection Concurrent participation in another therapeutic clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GS-9820<br>Participants will be sequentially enrolled at progressively higher dose levels to receive GS-9820 administered twice a day. Escalation will proceed to the maximum tolerated dose (MTD), defined as the highest tested dose associated with a rate of dose-limiting toxicities (DLT) of < 33% during the first 4 weeks of therapy. | Drug: GS-9820<br>* GS-9820 tablets containing 200 mg of GS-9820 administered orally<br>* Other names: CAL-120;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) | MTD will be assessed to determine the appropriate dosing regimens for use in future clinical trials of GS-9820 in subjects with lymphoid malignancies. | Up to 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall safety | Overall safety will be assessed by overall safety profile, enumeration and description of any dose-limiting toxicities, serious adverse events, or adverse events leading to discontinuation of study drug. | Up to 5 years | 
| Pharmacokinetic parameters of GS-9820 as measured by Cmax, Tmax, Ctrough, and AUC | Cmax is defined as the maximum concentration of drug Tmax is defined as the time of Cmax Ctrough is defined as the trough concentration AUC is defined as the area under the plasma concentration versus time curve | Baseline to Day 29 | 
| Pharmacodynamics to measure changes in the phosphatidylinositol 3-kinase (P13K) delta pathway activation and changes in plasma concentration of disease-associated chemokines and cytokines |  | Baseline to Day 29 | 
| Tumor control | Tumor control as assessed by overall response rate (ORR), time to response (TTR), duration of response (DOR), progression-free survival (PFS), percent change in lymph node area, lymph node response rate, splenomegaly response rate, ALC response rate, hepatomegaly response rate, platelet response rate, hemoglobin response rate, and neutrophil response rate. | Up to 5 years | 
| Patient well-being assessed using changes in baseline in HRQL (health related quality of life questionnaire) domain and symptom scores based on the Functional Assessment of Cancer Therapy: Lymphoma (FACT-Lym) |  | Up to 5 years | 
| Drug exposure | Drug administration for GS-9820 as assessed by prescribing records and GS-9820 compliance as assessed by quantification of used and unused drug. | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), indolent non-Hodgkin lymphoma (iNHL), diffuse large B-cell lymphoma-activated B-cell (DLBCL-ABC), DLBCL-germinal center B-cell (GCB), mantle cell lymphoma (MCL), GS-9820, phosphatidylinositol 3-kinase (PI3K)