Study of SGR-1505 in Mature B-Cell Neoplasms

Sponsor

Schrödinger, Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05544019

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: SGR-1505	Phase 1

Detailed Description

This is a study of SGR-1505 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

52 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Mar 1, 2024

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Escalation 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 SGR-1505 will be administered orally.
Experimental: FE/DDI Cohort 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 SGR-1505 will be administered orally.

Arm

Intervention/Treatment

Experimental: Dose Escalation

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

SGR-1505 will be administered orally.

Experimental: FE/DDI Cohort

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

SGR-1505 will be administered orally.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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).
Effect of Food on the Cmax of SGR-1505 [Throughout the study, up to 2 years.]
Plasma exposure parameters for SGR-1505 including, but not limited to, Cmax are evaluated following its administration with and without food.
Effect of Food on the tmax of SGR-1505 [Throughout the study, up to 2 years.]
Plasma exposure parameters for SGR-1505 including, but not limited to, tmax, are evaluated following its administration with and without food.
Effect of Food on the AUC of SGR-1505 [Throughout the study, up to 2 years.]
Plasma exposure parameters for SGR-1505 including, but not limited to, AUC are evaluated following its administration with and without food.
Effect of Posaconazole on the Cmax of SGR-1505 [Through study completion, up to 2 years.]
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.
Effect of Posaconazole on the tmax of SGR-1505 [Through study completion, up to 2 years.]
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.
Effect of Posaconazole on the AUC of SGR-1505 [Through study completion, up to 2 years.]
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.
Objective Response Rate (ORR) [Throughout the study, up to 2 years.]
Number of patients who have a complete response (CR) or partial response (PR) 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.