This is a multiphase, multicenter study, which includes a Phase 1a open-label, dose escalation monotherapy study of ST-067 given as an SC injection with or without obinutuzumab \[Gazyva®\] pre-treatment, by IV infusion, and in combination with pembrolizumab. A Phase 2 monotherapy arm is also planned; the exact design of the Phase 2 study elements with respect to formulation and pre-treatment will be determined after completion of the Phase 1 study portion of the trial.
Phase 1a is designed to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of ST067, administered by subcutaneous (SC) or intravenous (IV) dosing, in subjects with relapsed or refractory solid tumors, as well as to determine the MTD and recommended Phase 2 dose of ST067, administered SC with obinutuzumab (Gazyva®) as pretreatment in subjects with relapsed or refractory solid tumors using a modified toxicity probability interval (mTPI) design. There will be evaluations of ST-067 PK and PD effects. Phase 2 will evaluate the preliminary efficacy of ST-067 administered at the RP2D to patients with the following tumor types. A Simon 2 stage design is used to calculate the sample size and early stopping rules will be employed in the event of lack of efficacy in any of the cohorts. RECIST 1.1 will be used to assess tumor response every 8-12 weeks. * Melanoma (n=28) * Renal cell carcinoma (n=25) * Triple-negative best cancer (n=25) * Non-small cell lung cancer (n=25) * squamous cell carcinoma of the head and neck (n=28) * MSI-Hi tumors (n=25) A Simon 2 stage design is used to calculate the sample size and early stopping rules will be employed in the event of lack of efficacy in any of the cohorts. RECIST 1.1 will be used to assess tumor response every 8-12 weeks. Safety will be assessed for each patient throughout the study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
316
ST-067 is an engineered variant of human interleukin-18.
Obinutuzumab is a humanized anti-CD20 monoclonal antibody of the IgG1 subclass. It recognizes a specific epitope of the CD20 molecule found on B-cells.
Pembrolizumab is a potent humanized immunoglobulin G4 monoclonal antibody.
HonorHealth Research Institute
Scottsdale, Arizona, United States
RECRUITINGSarah Cannon Research Institute at HealthONE
Denver, Colorado, United States
RECRUITINGYale Cancer Center
New Haven, Connecticut, United States
RECRUITINGMoffitt Cancer Center
Tampa, Florida, United States
RECRUITINGMassachusetts General Hospital
Boston, Massachusetts, United States
RECRUITINGRoswell Park Cancer Institute
Buffalo, New York, United States
RECRUITINGDetermine the maximum tolerated dose of ST-067 in phase 1a monotherapy
Patients will be enrolled at a dose level that is predicted to be the MTD
Time frame: Day 29
Evaluate the overall safety and tolerability of ST-067 in combination with pembrolizumab
In patients experiencing insufficient response to a checkpoint inhibitor (PD-1) therapy administered alone or in combination.
Time frame: Day 29
Number of Participants With Treatment-Related Adverse Events
AE assessed by CTCAE 5.0
Time frame: Day 29
Initial assessment of efficacy in phase 2
Investigator-assessed ORR, defined as either a complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 based on computed tomography (CT) or magnetic resonance imaging (MRI) scans
Time frame: At 8 weeks
PK
Peak Plasma Concentration (Cmax)
Time frame: Day 29
ADA
Incidence of ADA to ST-067
Time frame: Day 29
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