Study of IT STX-001 in Patients With Advanced Solid Tumors as Monotherapy or in Combination With Pembrolizumab

• ClinicalTrials.gov Identifier: NCT06249048
• Recruitment Status: Recruiting
• First Posted: February 8, 2024
• Last Update Posted: May 9, 2024
• Sponsor: Strand Therapeutics Inc.
• Information provided by (Responsible Party): Strand Therapeutics Inc.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumor	Biological: STX-001; Biological: Keytruda®	Phase 1; Phase 2

Detailed Description:

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), and 4 planned dose escalation cohorts of STX-001 delivered as a combination therapy, with pembrolizumab treatment given concurrently (Cohorts 1c).

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. 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 108 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Ph 1/2 Open-label, Multi-center, FIH Study of Safety, Tolerability, Pharmacokinetics, Pharmacodynamics & Antitumor Activity of STX-001 Via Intratumoral Injection in Pts w Advanced Solid Tumors as Monotherapy or Combination w Pembrolizumab
• Actual Study Start Date: May 3, 2024
• Estimated Primary Completion Date: May 2027
• Estimated Study Completion Date: November 2028

Arms and Interventions

Arm	Intervention/treatment
Experimental: Phase 1 Monotherapy (STX-001); A Phase 1, first-in-human (FIH), multiple ascending STX-001 dose administration to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity in patients with advanced cancers. Consists of 4 planned dose escalation cohorts (Cohorts 1m) of STX-001 with new patients enrolled in each dose escalation cohort.	Biological: STX-001; STX-001 encapsulates a self-replicating RNA encoded for IL-12, contained within an LNP for intratumoral injection.
Experimental: Phase 1 Combination (STX-001 with Pembrolizumab); A Phase 1, first-in-human (FIH), multiple ascending STX-001 dose administration, in combination with pembrolizumab, to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity in patients with advanced cancers. Consists of 4 planned dose escalation cohorts (Cohorts 1c) of STX-001 with new patients enrolled in each dose escalation cohort.	Biological: STX-001; STX-001 encapsulates a self-replicating RNA encoded for IL-12, contained within an LNP for intratumoral injection.; Biological: Keytruda®; Pembrolizumab (Keytruda USPI 2023) is a marketed PD-1 blocking humanized monoclonal IgG4 kappa antibody.; Other Name: Pembrolizumab
Experimental: Phase 2 Combination (STX-001 with Pembrolizumab); Phase 2 consists of dose expansion cohorts in patients with 2 defined cancer types: triple negative breast cancer (TNBC) and melanoma. Phase 2 will evaluate STX-001 in combination with pembrolizumab; the recommended Phase 2 dose (RP2D) of STX-001 will be selected based on analysis of the totality of data from Phase 1.	Biological: STX-001; STX-001 encapsulates a self-replicating RNA encoded for IL-12, contained within an LNP for intratumoral injection.; Biological: Keytruda®; Pembrolizumab (Keytruda USPI 2023) is a marketed PD-1 blocking humanized monoclonal IgG4 kappa antibody.; Other Name: Pembrolizumab

Outcome Measures

Primary Outcome Measures :

1. Number and nature of dose-limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) in subjects with advanced solid tumors. [ Time Frame: From time of informed consent until 30 days after the last dose of investigational product (STX-001). ]
   The occurrence of DLTs, TEAEs, and SAEs will be used to determine the maximum tolerated dose and recommended Phase 2 dose of STX-001.
2. Occurrence of changes from baseline in subjects' clinical safety laboratory values and vital signs to assess the safety and tolerability of STX-001. [ Time Frame: From time of informed consent until 30 days after the last dose of investigational product (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).

Secondary Outcome Measures :

1. Assessment of PK in patients dosed with STX-001 [ Time Frame: From time of informed consent until 30 days after the last dose of investigational product (STX-001). ]
   Individual and mean plasma STX-001 concentrations versus time data will be collected, summarized, and plotted by dose level.
2. Number and nature of preliminary antitumor activity of STX-001. [ Time Frame: From time of informed consent until 30 days after the last dose of investigational product (STX-001). ]
   Proportion of subjects with objective response rate (ORR), complete response (CR), or partial response (PR) per RECIST 1.1.
3. Number and nature of preliminary antitumor activity of STX-001 in combination with pembrolizumab. [ Time Frame: From time of informed consent until 30 days after the last dose of investigational product (STX-001). ]
   Proportion of subjects with objective response rate (ORR), complete response (CR), or partial response (PR) per RECIST 1.1.
4. Number and nature of preliminary antitumor activity of STX-001. [ Time Frame: From time of informed consent until 30 days after the last dose of investigational product (STX-001). ]
   Proportion of subjects with disease control rate (DCR) (CR, PR or stable disease [SD]) per RECIST 1.1.
5. Number and nature of preliminary antitumor activity of STX-001 in combination with pembrolizumab. [ Time Frame: From time of informed consent until 30 days after the last dose of investigational product (STX-001). ]
   Proportion of subjects with disease control rate (DCR) (CR, PR or stable disease [SD]) per RECIST 1.1.
6. Number and nature of preliminary antitumor activity of STX-001. [ Time Frame: From time of informed consent until 18 months after the last dose of investigational product (STX-001). ]
   Proportion of subjects with duration of response (DOR) (CR or PR), per RECIST 1.1.
7. Number and nature of preliminary antitumor activity of STX-001 in combination with pembrolizumab. [ Time Frame: From time of informed consent until 18 months after the last dose of investigational product (STX-001). ]
   Proportion of subjects with duration of response (DOR) (CR or PR), per RECIST 1.1.
8. Number and nature of preliminary antitumor activity of STX-001. [ Time Frame: From time of informed consent until 18 months after the last dose of investigational product (STX-001). ]
   Proportion of subjects with progression-free survival (PFS), defined as the time from randomization to first evidence of radiographically detectable disease or death from any cause.
9. Number and nature of preliminary antitumor activity of STX-001 in combination with pembrolizumab. [ Time Frame: From time of informed consent until 18 months after the last dose of investigational product (STX-001). ]
   Proportion of subjects with progression-free survival (PFS), defined as the time from randomization to first evidence of radiographically detectable disease or death from any cause.
10. Number and nature of preliminary antitumor activity of STX-001. [ Time Frame: From time of informed consent until 18 months after the last dose of investigational product (STX-001). ]
    Proportion of subjects with overall survival (OS).
11. Number and nature of preliminary antitumor activity of STX-001 in combination with pembrolizumab. [ Time Frame: From time of informed consent until 18 months after the last dose of investigational product (STX-001). ]
    Proportion of subjects with overall survival (OS).
12. Occurrence of TEAEs, SAEs, and AESIs graded according to NCI CTCAE v5.0 [ Time Frame: From time of informed consent until 30 days after the last dose of investigational product (STX-001). ]
    Assessment of the safety and tolerability of STX-001 in patients with advanced solid tumors.
13. Occurrence of changes from baseline in subjects' clinical safety laboratory values and vital signs to assess the safety and tolerability of STX-001.in combination with pembrolizumab. [ Time Frame: From time of informed consent until 30 days after the last dose of investigational product (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).
14. Objective Response Rate (ORR) 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). ]
    Objective Response Rate (ORR) is defined as the proportion of subjects with confirmed response (CR) or confirmed partial response (PR).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

General Inclusion Criteria:

• ≥ 18 years of age at the time of screening.
• Mentally competent and able to understand and sign the informed consent form (ICF).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy of ≥ 12 weeks per the Investigator.
• Body weight ˃ 40 kg.
• At least 4 weeks from any prior major surgery.
• Willing and able to provide blood samples prior to the start of this study.
• Has a tumor lesion amenable to injection (must be ≥ 1 cm in diameter and accessible by direct palpation or ultrasound; must not be located adjacent to vital structures, including airways, major nerves, or blood vessels; the lesion for injection) must be accessible for pre and post injection biopsy, and the patient must be willing to consent to biopsy, if deemed safe by the Investigator.
• Laboratory values (Hematology): Absolute neutrophil count ≥ 1,000 cells/mm3; Platelet count ≥ 75,000 cells/mm3; Hemoglobin ≥ 8.0 g/dL.
• Laboratory values (Renal): Serum creatinine < 1.5 × upper limit of normal (ULN) or creatinine clearance ≥ 40 mL/min based on the Cockcroft-Gault glomerular filtration rate estimation
• Laboratory values (Coagulation): International Normalized Ratio (INR) must be < 1.5 × ULN; Prothrombin time or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN unless undergoing anticoagulation therapy.
• Laboratory values (Liver): Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2 × ULN; Bilirubin ≤ 2 × ULN or ≤ 5 × ULN with liver metastasis.

Phase 1 Inclusion Criteria:

• Histologically or cytologically documented, locally advanced, or metastatic solid tumor.
• Disease progression confirmed by imaging or other objective evidence after having received standard treatment or patients with refractory solid tumors. Patients must have progressed or are intolerant of at least one line of prior therapy.

Phase 2 Inclusion Criteria (TNBC):

• Histologically or cytologically documented findings consistent with TNBC not amenable to curative surgery, radiation, or other therapy.
• Prior treatment (for advanced, metastatic or [neo]adjuvant) should have included a taxane and/or anthracycline-based therapy and, where appropriate, an approved checkpoint inhibitor.
• Has disease other than the injected lesion that is measurable by RECIST 1.1.

Phase 2 Inclusion Criteria (melanoma):

• Histologically or cytologically documented findings consistent with advanced melanoma not amenable to curative surgery, radiation, or other therapy. Uveal melanoma is excluded.
• Patients who are not candidates for or have refused available therapies are also eligible.
• Received an anti-programmed death-1 (PD-1) / programmed death ligand-1 (PD-L1) inhibitor as monotherapy or in combination with anti-cytotoxic lymphocyte associated protein 4 (CTLA-4) inhibitor and have either primary or secondary checkpoint inhibitor resistance as per Society for Immunotherapy of Cancer (SITC) consensus definition, unless deemed intolerable by the investigator. Patients with BRAF V600E mutant melanoma should have received a BRAF inhibitor as monotherapy or in combination with other targeted agents (mitogen-activated protein kinase [MAPK] kinase [MEK] inhibitors), unless deemed intolerable by the investigator.
• Has disease other than the injected lesion that is measurable by RECIST 1.1.

Phase 1 and 2 Exclusion Criteria:

• History of autoimmune disease and/or requiring immunosuppression (except hypothyroidism).
• History of solid organ transplant.
• Cardiovascular exclusions: Medical history of an arterial thrombotic event, stroke, or transient ischemic attack within the past 12 months; medical history of symptomatic congestive heart failure (New York Heart Association classes II-IV) or a cardiac arrhythmia that required treatment within the past 12 months; medical history of myocardial infarction or unstable angina within 6 months before Cycle 1 Day 1; QTcF prolongation to > 470 ms in women and > 450 ms in men based on a 12-lead electrocardiogram (ECG) in triplicate using the Fridericia formula: QTc = QT / RR1/3.
• Evidence of active infection requiring intravenous (IV) antibiotics during screening requiring therapy within 7 days prior to Cycle 1 Day 1.
• Active uncontrolled bleeding, or a bleeding diathesis within 7 days prior to Cycle 1 Day 1.
• Serious or non-healing wound, fistula, skin ulcer, or non-healing bone fracture within 7 days prior to Cycle 1 Day 1.
• Known human immunodeficiency virus (HIV) infection, active hepatitis B infection, or hepatitis C infection.
• Untreated central nervous system tumor, epidural tumor or metastasis, or brain metastasis.
• Another primary malignancy that has not been treated with curative intent, except for non-metastatic cutaneous basal cell or squamous cell carcinoma, or non-muscle invasive bladder cancer.
• Serious illness considered by the Investigator as incompatible with participating in this clinical study.
• Any condition that, in the opinion of the Investigator, would interfere with evaluation of the investigational product or interpretation of the patient's safety or study results.
• Prior IL-12 therapy.
• Receipt of any vaccine within 30 days prior to the first dose of study treatment.
• Use of another anticancer therapy within 3 weeks prior to Cycle 1 Day 1 or 5 half-lives, whichever is shorter.
• Previously enrolled in this study.
• Actively enrolled in another clinical study unless it is an observational (noninterventional) clinical study or the follow-up component of an interventional study.
• Known severe hypersensitivity (Grade ≥ 3) to study treatment or any of the excipients of the products.
• Known psychiatric or substance use disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
• Currently pregnant (confirmed with positive pregnancy test), breast-feeding or planning to become pregnant. For women of childbearing potential (WOCBP), a negative serum beta-human chorionic gonadotropin (β-HCG) result must be in place within 72 hours of first treatment dose.
• Women of childbearing potential not willing to use a highly effective method of contraception.
• Unwilling or unable to follow protocol requirements.

Contacts and Locations

Locations

United States, California

NextGen Oncology; Recruiting

Beverly Hills, California, United States, 90212

Contact: Mini Gill 424-777-0708 MiniG@NextGenOnc.com

United States, Pennsylvania

University of Pittsburgh Medical Center; Not yet recruiting

Pittsburgh, Pennsylvania, United States, 15232

Contact: Julie Urban 412-623-7396 Urbanj2@upmc.edu

United States, Texas

The University of Texas MD Anderson Cancer Center; Not yet recruiting

Houston, Texas, United States, 77030

Contact: Rabia Khan 713-563-4667 RKhan@mdanderson.org

Australia

Melanoma Institute Australia; Not yet recruiting

Wollstonecraft, Australia

Contact: Maria Gonzalez 0299117300 maria.gonzalez@melanoma.org.au

Sponsors and Collaborators

Strand Therapeutics Inc.

Investigators

• Study Chair: Tasuku A Kitada, PhD; Strand Therapeutics

More Information

• Responsible Party: Strand Therapeutics Inc.
• ClinicalTrials.gov Identifier: NCT06249048
• Other Study ID Numbers: STX-001-01
• First Posted: February 8, 2024
• Last Update Posted: May 9, 2024
• Last Verified: May 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Strand Therapeutics Inc.:

Intratumoral; Cancer; Solid Tumors; mRNA

Additional relevant MeSH terms:

Neoplasms; Pembrolizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action