Study of SGR-1505 in Mature B-Cell Neoplasms

Study Overview
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Brief Summary
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The purpose of this study is to evaluate safety and tolerability and to determine the maximum tolerated dose (MTD) and/or recommended dose (RD) of SGR-1505.

Detailed Description
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This is a study of SGR-1505, an oral inhibitor of MALT1, in subjects with relapsed/refractory (R/R) B-cell lymphomas to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), maximum tolerated dose (MTD) and/or recommended dose (RD) of SGR-1505. Exploratory cohorts will evaluate additional PK, PD, preliminary anti-tumor activity, and safety to establish the SGR-1505 RD. A sub-study will evaluate the effect of food and drug-drug interactions. A planned amendment will evaluate SGR-1505 in combination with other anti-cancer agents, such as BTK and BCL-2 inhibitors, in patients with specific B-cell malignancies.

Official Title
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A Phase 1, Open-Label, Multicenter, Dose Escalation Study of SGR-1505 as Monotherapy in Subjects With Mature B-Cell Malignancies

Conditions
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Mature B-Cell Neoplasm, Non Hodgkin Lymphoma, DLBCL, Waldenstrom Macroglobulinemia, MALT Lymphoma, Follicular Lymphoma, Pediatric-Type Follicular Lymphoma, IRF4 Gene Rearrangement, EBV-Positive DLBCL, Nos, Burkitt Lymphoma, Plasmablastic Lymphoma, High-grade B-cell Lymphoma, Primary Cutaneous Follicle Center Lymphoma, Primary Effusion Lymphoma, Mantle Cell Lymphoma, DLBCL Germinal Center B-Cell Type, Primary Mediastinal Large B Cell Lymphoma, T-Cell/Histiocyte Rich Lymphoma, ALK-Positive Large B-Cell Lymphoma, Primary Cutaneous Diffuse Large B-Cell Lymphoma, Splenic Marginal Zone Lymphoma, Chronic Lymphocytic Leukemia, Nodal Marginal Zone Lymphoma, HHV8-Positive DLBCL, Nos, Lymphoplasmacytic Lymphoma, Duodenal-Type Follicular Lymphoma

Intervention / Treatment
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* Drug: SGR-1505


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must have a history of histologically or cytologically confirmed mature B-cell malignancy. Subject must have measurable or detectable disease according to the applicable disease-specific classification system. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. Life expectancy ≥ 12 weeks. Exclusion Criteria: For a subject with indolent NHL and CLL/SLL, the subject is in need of immediate cytoreductive therapy (unless the patient has no remaining treatment choice with potential benefit) and has an indication for treatment. Subject has previous invasive malignancy in the last 2 years. Subject has a known allergy to SGR-1505 or excipients of SGR-1505. Subject has symptomatic or active CNS involvement of disease. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that would place the participant at increased risk to the use of an investigational drug.

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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation<br>Up to 11 dose levels will be evaluated. Eligible patients will be assigned to a dose level cohort according to an accelerated titration design that will transition to a traditional 3+3 dose escalation. | Drug: SGR-1505<br>* SGR-1505 will be administered orally.<br>|
| Experimental: FE/DDI Cohort<br>Participants will be dosed in a fed (high-fat, high-calorie meal) and fasted state to determine the effect of food on bioavailability of SGR-1505. Participants will be dosed with and without Posaconazole to determine the effect on the exposure of SGR-1505. | Drug: SGR-1505<br>* SGR-1505 will be administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nature, severity, and number of incidences of adverse events (AEs), serious AEs (SAEs), and AEs leading to treatment discontinuation. |  | Throughout the study, up to 2 years. | 
| Nature and number of incidences of dose limiting toxicity (DLT). | A DLT is an AE that requires treatment interruption. | The first 21 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SGR-1505 Maximal Plasma Concentration (Cmax) | Concentrations of SGR-1505 in plasma are measured at various timepoints following its administration to calculate typical exposure/PK parameters, including, but not limited to, the maximal plasma concentration (Cmax). | Through study completion, up to 2 years. | 
| SGR-1505 Time to Maximal Plasma Concentration (tmax) | Concentrations of SGR-1505 in plasma are measured at various timepoints following its administration to calculate typical exposure/PK parameters, including, but not limited to, the time to maximal plasma concentration (tmax). | Through study completion, up to 2 years. | 
| SGR-1505 Area Under the Concentration Versus Time Curve (AUC) | Concentrations of SGR-1505 in plasma are measured at various timepoints following its administration to calculate typical exposure/PK parameters, including, but not limited to, the area under the concentration versus time curve (AUC). | Through study completion, up to 2 years. | 
| Effect of Food on the Cmax of SGR-1505 | Plasma exposure parameters for SGR-1505 including, but not limited to, Cmax are evaluated following its administration with and without food. | Throughout the study, up to 2 years. | 
| Effect of Food on the tmax of SGR-1505 | Plasma exposure parameters for SGR-1505 including, but not limited to, tmax, are evaluated following its administration with and without food. | Throughout the study, up to 2 years. | 
| Effect of Food on the AUC of SGR-1505 | Plasma exposure parameters for SGR-1505 including, but not limited to, AUC are evaluated following its administration with and without food. | Throughout the study, up to 2 years. | 
| Effect of Posaconazole on the Cmax of SGR-1505 | Plasma exposure parameters for SGR-1505 including, but not limited to, Cmax are evaluated following its administration alone and after co-administration with Posaconazole, a typical CYP3A4 inhibitor. | Through study completion, up to 2 years. | 
| Effect of Posaconazole on the tmax of SGR-1505 | Plasma exposure parameters for SGR-1505 including, but not limited to, tmax, are evaluated following its administration alone and after co-administration with Posaconazole, a typical CYP3A4 inhibitor. | Through study completion, up to 2 years. | 
| Effect of Posaconazole on the AUC of SGR-1505 | Plasma exposure parameters for SGR-1505 including, but not limited to, AUC are evaluated following its administration alone and after co-administration with Posaconazole, a typical CYP3A4 inhibitor. | Through study completion, up to 2 years. | 
| Objective Response Rate (ORR) | Number of patients who have a complete response (CR) or partial response (PR) to treatment. | Throughout the study, up to 2 years. | 
| Duration of Response (DOR) | The time from response CR/PR until relapse or death from any cause. | Throughout the study, up to 2 years. | 
| Disease Control Rate | PR, CR, and SD for 2 post-baseline disease assessments at least 6 weeks apart. | Throughout the study, up to 2 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MALT1, NF-kB