Phase 1 Study of Intratumoral Administration of VAX014 in Subjects With Advanced Solid Tumors

Primary Outcome Measures:

• Maximum tolerated dose (MTD) of VAX014

Time Frame: Up to 28 days

• Incidence of Treatment-Emergency Adverse Events (Safety and Tolerability)

Time Frame: Through study completion, an average of 20 weeks

• Recommended Phase 2 Dose (RP2D) of intratumoral VAX014

Time Frame: Up to 5 weeks

Inclusion Criteria:

1. Age 18+
2. Informed consent
3. Diagnosis of solid tumor(s) relapsed or refractory to standard treatments
4. Histological or cytopathological confirmed diagnosis of a locally advanced or metastatic solid tumor that is not appropriate for resection and for which systemic treatment is not appropriate (per Investigator)
5. Progression following at least one prior standard treatment or intolerant of standard treatments.
6. No available SOC therapy that would confer clinical benefit
7. [Dose escalation] At least one cutaneous, subcutaneous, or nodal injectable tumor (between 1 and 10 cm in largest diameter) that can be injected by direct palpation or with the assistance of ultrasound without the need for interventional radiology
8. [Expansion] At least one cutaneous, subcutaneous, nodal or metastatic injectable tumor (between 1 and 10 cm in largest diameter) that can be injected either with or without the need for interventional radiology
9. Measurable disease by RECIST v1.1
10. ECOG Performance Status of 0, 1, or 2
11. Adequate hematologic function defined as:
    1. Absolute neutrophil count >1,500/uL
    2. Platelet count >100,000/uL
12. Adequate hepatic function defined as:
    1. Total bilirubin ≤ 1.5 x ULN
    2. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN
13. Serum creatinine ≤ 1.5 x ULN or estimated GFR ≥ 60 mL/min/1.73 m2 (per MDRD GFR formula)
14. Women of childbearing potential must have a negative serum pregnancy test
15. All subjects of childbearing potential must be willing to consent to using effective contraception (as determined by the investigator) while on treatment and for 3 months after their participation in the study ends

Exclusion Criteria:

1. Injectable tumor not sufficiently distanced from critical structures (e.g., major airway, neurovascular structure) where post injection swelling may place the subject at unacceptable risk
2. ≤ 28 days from prior anticancer therapy and C1D1 (e.g., chemotherapy, immunotherapy, intralesional therapy, irradiation therapy)
3. Known CNS metastases or leptomeningeal carcinomatosis, unless adequately treated and clinically stable off steroids for ≥ 14 days from C1D1
4. Known active infection requiring systemic antibiotic therapy
5. Concurrent use of warfarin, heparin, or chronic NSAID(s) use, including aspirin at > 81 mg daily, within 14 days of C1D1
6. Need for systemic immunosuppressive therapy
7. Any other malignancy likely to require treatment in the next 2 years (exceptions include cancer such as basal or squamous cell skin cancers, noninvasive cancer of the cervix, and local prostate cancer)
8. Requirement for immunosuppressive therapy (i.e., prednisone equivalent of > 10 mg/day)
9. Known immunodeficiency disorder
10. Known active Hepatitis B or C
11. Women who are pregnant or lactating
12. Medical or physiological condition that places the subject at undue risk with study participation