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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06249048




Registration number
NCT06249048
Ethics application status
Date submitted
2/02/2024
Date registered
8/02/2024
Date last updated
9/05/2024

Titles & IDs
Public title
Study of IT STX-001 in Patients With Advanced Solid Tumors as Monotherapy or in Combination With Pembrolizumab
Scientific 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
Secondary ID [1] 0 0
STX-001-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumor 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - STX-001
Other interventions - Keytruda®

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.

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.

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.


Other interventions: STX-001
STX-001 encapsulates a self-replicating RNA encoded for IL-12, contained within an LNP for intratumoral injection.

Other interventions: Keytruda®
Pembrolizumab (Keytruda USPI 2023) is a marketed PD-1 blocking humanized monoclonal IgG4 kappa antibody.
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number and nature of dose-limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) in subjects with advanced solid tumors.
Timepoint [1] 0 0
From time of informed consent until 30 days after the last dose of investigational product (STX-001).
Primary outcome [2] 0 0
Occurrence of changes from baseline in subjects' clinical safety laboratory values and vital signs to assess the safety and tolerability of STX-001.
Timepoint [2] 0 0
From time of informed consent until 30 days after the last dose of investigational product (STX-001).
Secondary outcome [1] 0 0
Assessment of PK in patients dosed with STX-001
Timepoint [1] 0 0
From time of informed consent until 30 days after the last dose of investigational product (STX-001).
Secondary outcome [2] 0 0
Number and nature of preliminary antitumor activity of STX-001.
Timepoint [2] 0 0
From time of informed consent until 30 days after the last dose of investigational product (STX-001).
Secondary outcome [3] 0 0
Number and nature of preliminary antitumor activity of STX-001 in combination with pembrolizumab.
Timepoint [3] 0 0
From time of informed consent until 30 days after the last dose of investigational product (STX-001).
Secondary outcome [4] 0 0
Number and nature of preliminary antitumor activity of STX-001.
Timepoint [4] 0 0
From time of informed consent until 30 days after the last dose of investigational product (STX-001).
Secondary outcome [5] 0 0
Number and nature of preliminary antitumor activity of STX-001 in combination with pembrolizumab.
Timepoint [5] 0 0
From time of informed consent until 30 days after the last dose of investigational product (STX-001).
Secondary outcome [6] 0 0
Number and nature of preliminary antitumor activity of STX-001.
Timepoint [6] 0 0
From time of informed consent until 18 months after the last dose of investigational product (STX-001).
Secondary outcome [7] 0 0
Number and nature of preliminary antitumor activity of STX-001 in combination with pembrolizumab.
Timepoint [7] 0 0
From time of informed consent until 18 months after the last dose of investigational product (STX-001).
Secondary outcome [8] 0 0
Number and nature of preliminary antitumor activity of STX-001.
Timepoint [8] 0 0
From time of informed consent until 18 months after the last dose of investigational product (STX-001).
Secondary outcome [9] 0 0
Number and nature of preliminary antitumor activity of STX-001 in combination with pembrolizumab.
Timepoint [9] 0 0
From time of informed consent until 18 months after the last dose of investigational product (STX-001).
Secondary outcome [10] 0 0
Number and nature of preliminary antitumor activity of STX-001.
Timepoint [10] 0 0
From time of informed consent until 18 months after the last dose of investigational product (STX-001).
Secondary outcome [11] 0 0
Number and nature of preliminary antitumor activity of STX-001 in combination with pembrolizumab.
Timepoint [11] 0 0
From time of informed consent until 18 months after the last dose of investigational product (STX-001).
Secondary outcome [12] 0 0
Occurrence of TEAEs, SAEs, and AESIs graded according to NCI CTCAE v5.0
Timepoint [12] 0 0
From time of informed consent until 30 days after the last dose of investigational product (STX-001).
Secondary outcome [13] 0 0
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.
Timepoint [13] 0 0
From time of informed consent until 30 days after the last dose of investigational product (STX-001).
Secondary outcome [14] 0 0
Objective Response Rate (ORR) in patients with advanced solid tumors.
Timepoint [14] 0 0
From time of informed consent until 30 days after the last dose of investigational product (STX-001).

Eligibility
Key inclusion criteria
General

- = 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

- 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 (ß-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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/05/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/11/2028
Actual
Sample size
Target
108
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Melanoma Institute Australia - Wollstonecraft
Recruitment postcode(s) [1] 0 0
- Wollstonecraft
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Pennsylvania
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Strand Therapeutics Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/ct2/show/NCT06249048
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Tasuku A Kitada, PhD
Address 0 0
Strand Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT06249048