Phase 1/2, Open-label, Multi-center, First-in-human Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of STX-001 Delivered by Intratumoral Injection in Patients with Advanced Solid Tumors as a Monotherapy or in Combination with Pembrolizumab. The study now includes a monotherapy cohort targeting visceral lesions and a separate Phase 2 monotherapy cohort for advanced melanoma.
This open-label, Phase 1/2, first-in-human (FIH), multiple ascending dose and dose expansion study involves STX-001 administration, alone or in combination with pembrolizumab, to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity in patients with advanced cancers. Phase 1 consists of 4 planned dose escalation cohorts of STX-001 delivered as a monotherapy (Cohorts 1m), 4 planned dose escalation monotherapy cohorts of STX-001 delivered as a combination therapy with pembrolizumab treatment given concurrently (Cohorts 1c), and an additional monotherapy cohort targeting visceral lesions (Cohort 1vm) that will be evaluated at 30ug, 100ug and 300ug. New patients will be enrolled in each dose escalation cohort. Phase 2 consists of dose expansion cohorts in patients with 2 defined cancer types: triple-negative breast cancer (TNBC) and melanoma. There will also be a monotherapy cohort for advanced melanoma. Phase 2 will evaluate STX-001 in combination with pembrolizumab; the recommended Phase 2 dose (RP2D) will be selected based on analysis of the totality of data from Phase 1 safety, tolerability, PK, PD and preliminary efficacy data.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
108
STX-001 encapsulates a self-replicating RNA encoded for IL-12, contained within an LNP for intratumoral injection. Injections may be administered into multiple lesions according to protocol-defined procedures.
Pembrolizumab (Keytruda USPI 2023) is a marketed PD-1 blocking humanized monoclonal IgG4 kappa antibody.
HonorHealth Research and Innovation Institute
Scottsdale, Arizona, United States
NOT_YET_RECRUITINGNextGen Oncology
Beverly Hills, California, United States
RECRUITINGCleveland Clinic
Cleveland, Ohio, United States
NOT_YET_RECRUITINGUniversity of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States
RECRUITINGThe University of Texas MD Anderson Cancer Center
Houston, Texas, United States
RECRUITINGHuntsman Cancer Institute - University of Utah
Salt Lake City, Utah, United States
NOT_YET_RECRUITINGMelanoma Institute Australia
Wollstonecraft, Australia
RECRUITINGNumber and nature of dose-limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) in patients with advanced solid tumors.
The occurrence of DLTs, TEAEs, and SAEs will be used to determine the maximum tolerated dose and recommended Phase 2 dose of STX-001.
Time frame: From time of informed consent until 30 days after the last dose of investigational product (STX-001).
Occurrence of changes from baseline in patients' clinical safety laboratory values and vital signs to assess the safety and tolerability of STX-001.
Collection and analysis of changes in data from baseline of patients' vital signs (temperature, pulse, respiratory rate, blood pressure, oxygen saturation via pulse oximetry) as well as clinical safety laboratory values (chemistry, hematology, coagulation, complement (Bb \& C3a), urinalysis, and lipids).
Time frame: From time of informed consent until 30 days after the last dose of investigational product (STX-001).
Assessment of PK in patients dosed with STX-001
Individual and mean plasma STX-001 concentrations versus time data will be collected, summarized, and plotted by dose level.
Time frame: From time of informed consent until 30 days after the last dose of investigational product (STX-001).
Assessment of Tumor infiltrating lymphocytes (TILs)
Assessment of STX-001 PK concentrations in mono therapy and safety and tolerability of STX-001 in combination with pembrolizumab in the tumor microenvironment (biopsy).
Time frame: From time of informed consent until 30 days after the last dose of investigational product (STX-001).
Number and nature of preliminary antitumor activity of STX-001.
Proportion of patients with objective response rate (ORR), complete response (CR), or partial response (PR) per RECIST 1.1.
Time frame: From time of informed consent until 30 days after the last dose of investigational product (STX-001).
Number and nature of preliminary antitumor activity of STX-001 in combination with pembrolizumab.
Proportion of patients with objective response rate (ORR), disease control rate (DCR), complete response (CR), partial response (PR) or stable disease (SD) per RECIST 1.1.
Time frame: From time of informed consent until 30 days after the last dose of investigational product (STX-001).
Number and nature of preliminary antitumor activity of STX-001.
Proportion of patients with progression-free survival (PFS), defined as the time from randomization to first evidence of radiographically detectable disease or death from any cause. Proportion of patients with duration of response (DOR) (CR or PR), per RECIST 1.1.
Time frame: From time of informed consent until 18 months after the last dose of investigational product (STX-001).
Number and nature of preliminary antitumor activity of STX-001 in combination with pembrolizumab.
Proportion of patients with progression-free survival (PFS), defined as the time from randomization to first evidence of radiographically detectable disease or death from any cause. Proportion of patients with overall survival (OS, duration of response (DOR) (CR or PR), per RECIST 1.1.
Time frame: From time of informed consent until 18 months after the last dose of investigational product (STX-001).
Occurrence of TEAEs, SAEs, and AESIs graded according to NCI CTCAE v5.0
Assessment of the safety and tolerability of STX-001 in patients with advanced solid tumors.
Time frame: From time of informed consent until 30 days after the last dose of investigational product (STX-001).
Occurrence of changes from baseline in patients' clinical safety laboratory values and vital signs to assess the safety and tolerability of STX-001.in combination with pembrolizumab.
Collection and analysis of changes in data from baseline of patients' vital signs (temperature, pulse, respiratory rate, blood pressure, oxygen saturation via pulse oximetry) as well as clinical safety laboratory values (chemistry, hematology, coagulation, complement (Bb \& C3a), urinalysis, and lipids).
Time frame: From time of informed consent until 30 days after the last dose of investigational product (STX-001).
Objective Response Rate (ORR) in patients with advanced solid tumors.
Objective Response Rate (ORR) is defined as the proportion of patients with confirmed response (CR) or confirmed partial response (PR).
Time frame: From time of informed consent until 30 days after the last dose of investigational product (STX-001).
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