A 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
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.
• ≥ 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 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): Prothrombin/International Normalized Ratio (PT/INR) or prothrombin time must be \< 1.5 × ULN;
• 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 for all patients.
⁃ 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.