ALK-Positive Large B-Cell Lymphoma, Burkitt Lymphoma, Chronic Lymphocytic Leukemia, DLBCL, DLBCL Germinal Center B-Cell Type, Duodenal-Type Follicular Lymphoma, EBV-Positive DLBCL, Nos, Follicular Lymphoma, HHV8-Positive DLBCL, Nos, High-grade B-cell Lymphoma, IRF4 Gene Rearrangement, Lymphoplasmacytic Lymphoma, MALT Lymphoma, Mantle Cell Lymphoma, Mature B-Cell Neoplasm, Nodal Marginal Zone Lymphoma, Non Hodgkin Lymphoma, Pediatric-Type Follicular Lymphoma, Plasmablastic Lymphoma, Primary Cutaneous Diffuse Large B-Cell Lymphoma, Primary Cutaneous Follicle Center Lymphoma, Primary Effusion Lymphoma, Primary Mediastinal Large B Cell Lymphoma, Splenic Marginal Zone Lymphoma, T-Cell/Histiocyte Rich Lymphoma, Waldenstrom Macroglobulinemia
Conditions
Keywords
MALT1, NF-kB, Waldenstrom Macroglobulinemia
Brief summary
The purpose of this study is to evaluate safety and tolerability and to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and/or recommended dose (RD) of SGR-1505.
Detailed description
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) or maximum administered dose (MAD) 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 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.
Interventions
DRUGSGR-1505
SGR-1505 will be administered orally.
Sponsors
Schrödinger, Inc.
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
* 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 and meet criteria for initiation of treatment. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Life expectancy ≥ 12 weeks.
Exclusion criteria
* The subject is in need of immediate cytoreductive therapy (unless the patient has no remaining treatment choice with potential benefit). * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). | The first 21 days. | A DLT is an AE that requires treatment interruption. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SGR-1505 Maximal Plasma Concentration (Cmax) | Through study completion, up to 2 years. | 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). |
| SGR-1505 Time to Maximal Plasma Concentration (tmax) | Through study completion, up to 2 years. | 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). |
| SGR-1505 Area Under the Concentration Versus Time Curve (AUC) | Through study completion, up to 2 years. | 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). |
| Objective Response Rate (ORR) | Throughout the study, up to 2 years. | Number of patients who have an objective response per response criteria other than stable disease (SD) or progressive disease (PD) to treatment. |
| Duration of Response (DOR) | Throughout the study, up to 2 years. | The time from response CR/PR until relapse or death from any cause. |
| Disease Control Rate | Throughout the study, up to 2 years. | PR, CR, and SD for 2 post-baseline disease assessments at least 6 weeks apart. |
Countries
France, Italy, Moldova, Poland, Romania, Spain, Ukraine, United States
Contacts
CONTACTStudy Physician
STUDY_DIRECTORFrank G Basile, M.D.
Schrodinger Inc.
Outcome results
None listed