Phase 1/2 Study of Intravenous Injection of STX-003 in Advanced Solid Tumors as Monotherapy or in Combination With Pembrolizumab

A Phase 1/2, Open-label, Multi-center, First-in-human Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Antitumor Activity of STX-003 Delivered Intravenously in Patients With Advanced Solid Tumors as a Monotherapy or in Combination With Pembrolizumab

Phase 1/2, Open-label, Multi-center, First-in-human Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of STX-003 Delivered by Intravenous Injection in Patients with Advanced Solid Tumors as a Monotherapy or in Combination with Pembrolizumab.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Biological: STX-003; Biological: KEYTRUDA®

Detailed Description

This open-label, Phase 1/2, first-in-human (FIH), multiple ascending dose and dose expansion study involves STX-003 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. (Update after review)

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jason Luke, MD, Chief Medical Officer; Phone Number: 617-993-9271; Email: stx-003-study@strandtx.com

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Recruiting
      • HonorHealth Research Institute
      • Principal Investigator: Justin Moser, MD
      • Contact: Amy Stolldastice; Phone Number: 602-570-2383; Email: astollstadice@honorhealth.com
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Institute
      • Principal Investigator: Melissa Johnson, MD
      • Contact: Ashley Maheu; Phone Number: 615-329-7274; Email: ashley.maheu@scri.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Inclusion Criteria (Phase 1 and Phase 2)

  1. Mentally competent and able to understand and sign the ICF.
  2. Tumor type for which there is an FDA-approved anti-PD-1/L1 antibody therapy, specifically including biomarker labeled subsets (i.e. PD-L1+) as well as anatomical subsets in some disease (cutaneous melanoma is eligible whereas acral, mucosal and uveal are not; Phase 1) and advanced cutaneous melanoma or PD-L1+ NSCLC.
  3. Histologically or cytologically documented, locally advanced, or metastatic solid tumor.
  4. At least one measurable lesion per RECIST v1.1 criteria.
  5. The patient lacks a curative therapy or has progressive disease despite, or refused, standard therapy.
  6. ECOG performance status of 0 or 1.
  7. Life expectancy of ≥ 12 weeks per the Investigator.
  8. ≥ 18 years of age at the time of informed consent.
  9. Body weight ≥ 40 kg.
  10. WOCBP and males with female partners of child-bearing potential must agree to use adequate birth control throughout their participation and for 3 months following the last dose of STX-003.
  11. Willing and able to comply with protocol required assessments.

Hematology:

• ANC ≥ 1,000 cells/mm3.
• Platelet count ≥ 75,000 cells/mm3.

• Hemoglobin ≥ 8.0 g/dL.

  • Renal: Serum creatinine < 1.5 × ULN or creatinine clearance ≥ 40 mL/min based on the Cockcroft-Gault glomerular filtration rate estimation

Coagulation:

• PT/INR or PT must be ≤ 1.5 × ULN.

• aPTT ≤ 1.5 × ULN unless undergoing anticoagulation therapy.

  • Liver:

• Albumin ≥ 3.5 g/dL or within the normal range of the local reference laboratory.
• AST and ALT < 2 × ULN.
• Bilirubin ≤ 1.5 × ULN (except participants with documented Gilbert's syndrome who may be enrolled if the conjugated bilirubin is within normal limits) or ≤ 5 × ULN with liver metastases.

Phase 2 Inclusion Criteria

13. NSCLC :

• Histologically or cytologically documented findings consistent with NSCLC not amenable to curative surgery, radiation, or other therapy.
• Biomarker confirmed as PD-L1+ per local institutional standard practice.
• Patients with known activating EGFR, STK11 or KEAP1 mutations as well as ALK/ROS1 fusions, are not eligible.

• Prior treatment (for advanced, metastatic or [neo]adjuvant) should have included a platinum-based therapy and a PD-1/L1 pathway checkpoint inhibitor, unless the patient is not a candidate for or has refused viable therapies due to inability to tolerate treatment (i.e. cell therapy) or potential side effects (i.e. checkpoint inhibitor toxicity).

  14. Melanoma : Histologically or cytologically documented findings consistent with advanced cutaneous melanoma not amenable to curative surgery, radiation, or other therapy. Acral, mucosal and uveal melanoma are excluded.

• Patients who are not candidates for or have refused available therapies due to inability to tolerate treatment (i.e. cell therapy) or potential side effects (i.e. checkpoint inhibitor toxicity) are also eligible.
• Received an anti-PD-1/PD-L1 inhibitor as monotherapy or in combination with anti-CTLA-4 inhibitor and have either primary or secondary checkpoint inhibitor resistance asper 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 (MAPK kinase MEK inhibitors), unless deemed intolerable by the Investigator.

Exclusion Criteria:

• Exclusion Criteria (Phase 1 and 2)

  1. Medical Conditions

     • History of primary immune deficiency.
     • History of clinically significant autoimmune disease that has required intervention in the last 6 months. Consultation with the MM may inform the discussion of whether autoimmune disease is clinically significant.
     • History of Grade 3 or higher IRAEs that has not resolved to Grade ≤ 1 at the time of enrollment. Exceptions include endocrine disorders that are well-managed with stable physiological hormone replacement and Grade 3 immune-related rash. Patients meeting this criterion may be considered for enrollment following approval by the MM.
     • History of solid organ transplant and taking immunosuppressive medications.

  2. Cardiovascular exclusions

     • Medical history of an arterial thrombotic event, stroke, or transient ischemic attack within the past 6 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 6 months.
     • Medical history of myocardial infarction or unstable angina within 6 months before C1D1.

  3. Recent medical concerns exclusions

     • Evidence of active infection requiring IV antibiotics within 7 days prior to C1D1.
     • Active uncontrolled bleeding, or a bleeding diathesis within 7 days prior to C1D1.
     • Serious or non-healing wound, fistula, skin ulcer, or non-healing bone fracture within 7 days prior to C1D1.
     • Known HIV infection, active hepatitis B infection, or hepatitis C infection:

• Virology evaluation should be conducted at Screening to include serum HIV antibody, HBc antibody, HBsAg antigen, and HCV antibody. Patients with a positive antibody evaluation for HCV and/or HBc should undergo evaluation to measure HCV RNA or HBV DNA, respectively.

  • Untreated CNS tumor, epidural tumor or metastasis, or brain metastasis. Patients with any primary CNS malignancy including glioma and current, active, or progressing CNS malignancy, including carcinomatosis meningitis, are excluded.
  • Patients with treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT scan) during the Screening period and are off systemic steroids (for at least 2 weeks prior to first dose).
  • Another primary malignancy that has not been treated with curative intent (discuss with MM), 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.
  • Major surgery within 4 weeks of first dose of study drug.

  • Any condition that, in the opinion of the Investigator, would interfere with evaluation of the investigational product or interpretation of the patients' safety or study results.

    4. Prior/Concomitant Therapy

  • Prior treatment with STX-003 or other VEEV-based replicating RNA.
  • Prior IL-12 therapy.
  • Receipt of any live vaccine within 30 days prior to the first dose of study treatment.
  • Use of another systemic anticancer therapy within 3 weeks prior to C1D1 or 5 halflives, whichever is shorter or use of radiotherapy within 1 week prior to C1D1 5. Prior/Concurrent Clinical Study Experience
  • 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.

Other Exclusions

• History of interstitial lung disease or active, non-infectious pneumonitis (combination cohorts only).
• Known psychiatric or substance use disorder that would interfere with the patient's ability to cooperate with the requirements of the study.
• Currently pregnant (confirmed with a positive pregnancy test), breast-feeding or planning to become pregnant within 6 months following treatment. For WOCBP, a negative serum β-HCG result must be available within a 72-hour window before the first treatment dose.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 Monotherapy; STX-003 administered intravenously, at ascending doses across sequential cohorts, once per cycle for up to 35 cycles (approximately 24 months).	Biological: STX-003; STX-003 is a LNP formulated self-replicating mRNA encoding the therapeutic payload human IL-12 (hIL-12) with miRNA target sites to sense specific endogenous miRs.
Experimental: Phase 1 Combination (STX-003 with Pembrolizumab); STX-003 administered intravenously, at ascending doses across sequential cohorts, once per cycle in combination with pembrolizumab for up to 35 cycles (approximately 24 months).	Biological: STX-003; STX-003 is a LNP formulated self-replicating mRNA encoding the therapeutic payload human IL-12 (hIL-12) with miRNA target sites to sense specific endogenous miRs.; Biological: KEYTRUDA®; Pembrolizumab (Keytruda USPI 2026) is a marketed PD-1 blocking humanized monoclonal IgG4 kappa antibody.
Experimental: Phase 2 Monotherapy (STX-003); STX-003 administered intravenously, at 4 planned dose expansion cohorts in patients with advanced cancers with high unmet need, once per cycle for up to 35 cycles (approximately 24 months).	Biological: STX-003; STX-003 is a LNP formulated self-replicating mRNA encoding the therapeutic payload human IL-12 (hIL-12) with miRNA target sites to sense specific endogenous miRs.
Experimental: Phase 2 Combination (STX-003 with Pembrolizumab); STX-003 administered intravenously, at 4 planned dose expansion cohorts in patients with advanced cancers with high unmet need, once per cycle for up to 35 cycles (approximately 24 months).	Biological: STX-003; STX-003 is a LNP formulated self-replicating mRNA encoding the therapeutic payload human IL-12 (hIL-12) with miRNA target sites to sense specific endogenous miRs.; Biological: KEYTRUDA®; Pembrolizumab (Keytruda USPI 2026) is a marketed PD-1 blocking humanized monoclonal IgG4 kappa antibody.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of TEAEs, SAEs, and DLTs		From time of informed consent until 30 days after the last dose of investigational product.
Occurrence of changes from baseline in patients' clinical safety laboratory values and vital signs to assess the safety and tolerability of STX-003.	Collection and analysis of changes in data from baseline of patients' safety laboratory values (chemistry, hematology, coagulation, complement (Bb & C3a), urinalysis, and lipids). Vital signs will include Temperature: (degrees Fahrenheit) Pulse: (beats per minute) Respiratory rate: (breaths per minute) Blood pressure: (systolic and diastolic each reported in mmHg) Oxygen saturation by pulse oximetry: (percentage (SpO2, %))	From Day 1 until 30 days after last dose of STX-003

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of PK and PD in patients dosed with STX-003	Area under the concentration curve (AUC)	Day 1,2,3,4,8,15,22,23,24,25,29,36, 43,44,51,58
Number and nature of preliminary antitumor activity of STX-003 as monotherapy and in combination with Pembrolizumab.		From time of informed consent until 30 days after the last dose of investigational product.
Assessment of Tumor infiltrating lymphocytes	Tumor biopsies will be analyzed by immunohistochemistry to assess tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment, including density of CD4 and CD8 positive cells and PD-L1 expression.	From time if informed consent until 30 days after the last dose of investigational product (STX-003)
Objective Response Rate (ORR) in patients with advanced solid tumors.		From time of informed consent until 30 days after the last dose of investigational product.
Assessment of PK and PD in patients dosed with STX-003	Maximum observed plasma concentration (Cmax) of STX-003	Day 1,2,3,4,8,15,22,23,24,25,29,36, 43,44,51,58
Changes from baseline in vital signs	Vital signs will include Temperature: (degrees Fahrenheit) Pulse: (beats per minute) Respiratory rate: (breaths per minute) Blood pressure: (systolic and diastolic each reported in mmHg) Oxygen saturation by pulse oximetry: (percentage (SpO2, %))	From Day 1 until 30 days after last dose of STX-003.

Collaborators and Investigators

• Sponsor: Strand Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2026
• Primary Completion (Estimated): July 17, 2030
• Study Completion (Estimated): November 15, 2030

Study Registration Dates

• First Submitted: April 6, 2026
• First Submitted That Met QC Criteria: August 3, 2026
• First Posted (Actual): August 6, 2026

Study Record Updates

• Last Update Posted (Actual): August 6, 2026
• Last Update Submitted That Met QC Criteria: August 3, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Non Small Cell Lung Cancer; Melanoma; Advanced Solid Tumors; mRNA; Intravenous
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Carcinoma, Non-Small-Cell Lung; Melanoma; pembrolizumab
• Other Study ID Numbers: STX-003-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No