NCT07222631

SB-4826 in Adult Participants With Locally Advanced or Metastatic Solid Tumors or Non-Hodgkin Lymphomas

An Open-Label, First-in-Human Phase 1/2, Dose-Escalation and Dose-Expansion/ Combination Therapy Study to Investigate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of SB-4826 as a Single Agent in Adult Participants With Locally Advanced or Metastatic Solid Tumors or Non-Hodgkin Lymphomas and in Combination With Rituximab in Adult Participants With Non-Hodgkin Lymphomas

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 48 (estimated)
• Sponsor: University of California, San Diego · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to learn what dose of the drug SB-4826 can be given safely in patients with solid tumors and non-Hodgkin lymphomas. This drug will be used alone in patients with solid tumors, and will be used alone or in combination with rituximab in patients with non-Hodgkin lymphomas. The main questions this clinical trial aims to answer are: What is the maximum dose of SB-4826 that can be used safely in patients with solid tumors and non-Hodgkin lymphomas, and will it work? How does SB-4826 work in people with cancer? How is SB-4826 absorbed, broken down, and excreted by the body? Participants will: Take drug SB-4826 twice weekly for up to 1 year; keep a diary of when they take SB-4826 at home; visit the clinic for checkups, tests, and fill out study questionnaires.

Detailed description

This is a first-in-human, phase 1/2, dose-escalation and dose-expansion / combination therapy study designed to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of the first-in-class orally bioavailable small ubiquitin-like modifier (SUMO) E1 inhibitor SB-4826, alone and in combination with rituximab (or biosimilar). SUMO E1 inhibitors are a class of anticancer therapies that activate anti-tumor immunity and can directly inhibit the proliferation and survival of cancer cells. SB-4826 is the first SUMO E1 inhibitor that acts through a covalent, allosteric, mechanism. Phase 1 (Dose-Escalation) Dose-escalation will include participants with locally advanced or metastatic solid tumors (other than tumors of the brain or central nervous system) or non-Hodgkin lymphoma. Participants with solid tumors will receive only SB-4826 monotherapy, while participants with non-Hodgkin lymphoma will receive either SB-4826 monotherapy or SB-4826 in combination with rituximab. Participants in the monotherapy treatment group will receive one of an anticipated seven dose-levels ranging from 20 to 600 mg SB-4826 twice weekly. The seven dose-escalation levels include: 20, 40, 80, 140, 240, 400, and up to 600 mg. The selection of the dose-level above 400 mg will be based on the review of the cumulative safety (through the dose-limiting toxicity period) and available pharmacokinetic and pharmacodynamic data from the previous treatment groups. The recommended phase 2 dose will be the optimal biological dose as determined by the sponsor/principal investigator (based on recommendation from the safety review committee) and consideration of all safety information (e.g., dose limiting toxicity, maximum tolerated dose, treatment-related adverse events) together with available pharmacokinetic, pharmacodynamic, and efficacy data. The recommended phase 2/optimal biological dose may be the maximum tolerated dose or may be a lower dose where optimal pharmacodynamic and pathway inhibition are observed. The recommended phase 2 dose will not exceed the maximum tolerated dose. Enrollment in the combination group will start after the recommended phase 2 dose is determined for the monotherapy group. Participants with non-Hodgkin lymphoma in the combination therapy group will receive one of up to 3 dose-levels of SB-4826 twice a week (beginning one dose-level below the monotherapy recommended phase 2 dose) plus rituximab. The recommended phase 2 dose for combination therapy will be determined independently and may be the same or different than the recommended phase 2 dose for monotherapy. In both phases, dose escalation will be based on a Bayesian Optimal Interval design with a target toxicity rate of 30%. The dose-escalation design will begin with SB-4826 as a single agent (monotherapy). Dose-escalation begins with a single participant enrolled at the first dose-level then proceeds to another single participant enrolled at the next dose-level until dose level 3 (80 mg) is reached or a Grade ≥ 2 adverse event is observed, regardless of attribution, at which time the cohort size switches to 3, and 2 additional participants are added at this dose level to complete the cohort of 3. Once the cohort size is increased to 3, dose escalation and de-escalation decisions are made as follows: If the observed dose limiting toxicity rate at the current dose is less than 23.6% then escalate; if the observed dose limiting toxicity rate at the current dose is greater than 35.8% then de-escalate; and if the observed dose limiting toxicity rate at the current dose is between 23.6% and 35.8%, then add new participants at the current dose. The process ends when either the maximum sample size of 21 has been reached or the sample size at the current dose level reaches the maximum of 12 and the dose limiting toxicity rate at this dose level is between 23.6% and 35.8%. Dose escalation in the combination cohort will proceed similarly, except that the initial cohort size is 3, and the maximum sample size is 9. The maximum tolerated dose is the dose-level determined by the Bayesian Optimal Interval design with a target toxicity rate of 30% within the first 21 days. Guided by the Bayesian Optimal Interval algorithm, the safety review committee, represented by the UCSD Moores Cancer Center Data and Safety Monitoring Committee, will make recommendations to the sponsor/principal investigator to proceed to the next dose-level or de-escalate to a previous dose-level. Additional responsibilities include making recommendations to add intermediate dose-levels, to add up to 6 additional participants at the anticipated recommended phase 2 dose/optimal biological dose prior to phase 2, to continue or suspend enrollment pending additional information, and making recommendations on defining the recommended phase 2 dose to be used in Phase 2 (Dose-Expansion/ Combination Therapy). Final decisions will be made by the sponsor/principal investigator. Dose limiting toxicities are pre-defined treatment-related adverse events occurring from first dose of study therapy up to and including Day 21. Treatment duration will be up to 1 year or until the participant exhibits disease progression, unacceptable toxicity, or other predefined discontinuation or withdrawal criteria are met, whichever occurs first. Phase 2 (Dose-Expansion/ Combination Therapy) Phase 2 will enroll only participants with non-Hodgkin lymphomas. They will receive SB-4826 twice a week at the recommended phase 2 dose found in phase 1, in combination with rituximab. Rituximab will be dosed at 375 mg/m\^2 intravenously weekly for the first cycle, and then at 375 mg/m\^2 intravenously on day 1 starting on cycle 2 for 6 cycles. After 6 cycles, responding participants will transition to maintenance rituximab every 9 weeks for up to 1 year. Treatment duration will be up to 1 year or until the participant exhibits disease progression, unacceptable toxicity, or other predefined discontinuation or withdrawal criteria are met, whichever occurs first.

Conditions

• Non Hodgkin Lymphoma
• Solid Tumor

Interventions

Type	Name	Description
DRUG	SB-4826	Small ubiquitin-like modifier E1 inhibitor
DRUG	Rituximab	Cluster of differentiation 20 blocker

Timeline

• Start date: 2026-02-18
• Primary completion: 2031-02-01
• Completion: 2033-02-01
• First posted: 2025-10-30
• Last updated: 2026-03-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study