Phase 1/2 Study of Intratumoral Injection of STX-001 in Advanced Solid Tumors as Monotherapy or in Combination With Pembrolizumab

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 accessible for pre and postinjection biopsy, and the patient must be willing to consent to biopsy, if deemedsafe 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) orcreatinine clearance ≥ 40 mL/min based on the Cockcroft-Gault glomerular filtrationrate 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 undergoinganticoagulation therapy.

• Laboratory values (Liver): Aspartate aminotransferase (AST) and alanineaminotransferase (ALT) < 2 × ULN; Bilirubin ≤ 2 × ULN or ≤ 5 × ULN with livermetastasis.

Phase 1 Inclusion Criteria:

• Histologically or cytologically documented, locally advanced, or metastatic solidtumor.

• Disease progression confirmed by imaging or other objective evidence after havingreceived standard treatment or patients with refractory solid tumors. Patients musthave 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 notamenable to curative surgery, radiation, or other therapy.

• Prior treatment (for advanced, metastatic or [neo]adjuvant) should have included ataxane and/or anthracycline-based therapy and, where appropriate, an approvedcheckpoint 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 advancedmelanoma not amenable to curative surgery, radiation, or other therapy. Uvealmelanoma is excluded.

• Patients who are not candidates for or have refused available therapies are alsoeligible.

• Received an anti-programmed death-1 (PD-1) / programmed death ligand-1 (PD-L1)inhibitor as monotherapy or in combination with anti-cytotoxic lymphocyte associatedprotein 4 (CTLA-4) inhibitor and have either primary or secondary checkpointinhibitor resistance as per Society for Immunotherapy of Cancer (SITC) consensusdefinition, unless deemed intolerable by the investigator. Patients with BRAF V600Emutant melanoma should have received a BRAF inhibitor as monotherapy or incombination 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 primary immune deficiency.

• History of autoimmune disease and/or requiring immunosuppression (excepthypothyroidism).

• History of History of Grade 3 or higher immune-related adverse events. Patient maybe enrolled with Medical Monitor approval.

• History of solid organ transplant and taking immunosuppressive medications.

• Cardiovascular exclusions: Medical history of an arterial thrombotic event, stroke,or transient ischemic attack within the past 12 months; medical history ofsymptomatic congestive heart failure (New York Heart Association classes II-IV) or acardiac arrhythmia that required treatment within the past 12 months; medicalhistory of myocardial infarction or unstable angina within 6 months before Cycle 1Day 1; QTcF prolongation to > 470 ms in women and > 450 ms in men based on a 12-leadelectrocardiogram (ECG) in triplicate using the Fridericia formula: QTc = QT /RR1/3.

Recent medical concerns exclusions:

• Prior direct radiation therapy to the tumor lesion to be injected.

• Active use of systemic anticoagulants

• Evidence of active infection requiring intravenous (IV) antibiotics during screeningrequiring therapy within 7 days prior to Cycle 1 Day 1.

• Active uncontrolled bleeding, or a bleeding diathesis within 7 days prior to Cycle 1Day 1.

• Serious or non-healing wound, fistula, skin ulcer, or non-healing bone fracturewithin 7 days prior to Cycle 1 Day 1.

• Known human immunodeficiency virus (HIV) infection, active hepatitis B infection, orhepatitis 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 antibodyevaluation for HCV and/or HBc should undergo evaluation to measure HCV RNA or HBVDNA, respectively.

• Untreated central nervous system tumor, epidural tumor or metastasis, or brainmetastasis. Patients with any primary Central Nervous System (CNS) malignancyincluding glioma and current, active, progressing CNS malignancy, includingcarcinomatosis meningitis are excluded.

• Patients with treated brain metastases are eligible if there is no evidence ofprogression for at least 4 weeks after CNS-directed treatment, as ascertained byclinical examination and brain imaging (magnetic resonance imaging [MRI] or computedtomography [CT] scan) during the screening period and off systemic steroids (for atleast 2 weeks prior to first dose).

• Another primary malignancy that has not been treated with curative intent, exceptfor non-metastatic cutaneous basal cell or squamous cell carcinoma, or non-muscleinvasive bladder cancer.

• Serious illness considered by the Investigator as incompatible with participating inthis clinical study.

• Any condition that, in the opinion of the Investigator, would interfere withevaluation of the investigational product or interpretation of the patient's safetyor 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 5half-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 interventionalstudy.

• Known severe hypersensitivity (Grade ≥ 3) to study treatment or any of theexcipients of the products.

• Known psychiatric or substance use disorder that would interfere with theparticipant's ability to cooperate with the requirements of the study.

• Currently pregnant (confirmed with positive pregnancy test), breast-feeding orplanning to become pregnant within 60 days following treatment. For women ofchildbearing potential (WOCBP), a negative serum beta-human chorionic gonadotropin (β-HCG) result must be available within a 72 hour window before the first treatmentdose.

• Women of childbearing potential not willing to use a highly effective method ofcontraception.

• Unwilling or unable to follow protocol requirements.