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

The purpose of this research study is to evaluate the safety, tolerability and activity of VAX014 for intratumoral injections (VAX014) in patients with advanced solid tumors. VAX014 is a targeted oncolytic agent designed to kill tumor cells following intratumoral injection into advanced solid tumors.

This study will evaluate the safety and tolerability of VAX014 using a 3+3 dose escalation design to determine a maximum tolerated dose (MTD) followed by a dose expansion at the Recommended Phase 2 Dose (RP2D). The DLT assessment period will be the initial 21-days of injections. Subjects will receive weekly injections for the initial 8 weeks. Up to six dose levels will be evaluated (i.e., \[starting dose\], \[starting dose\] x 3, \[starting dose\] x 10, \[starting dose\] x 30, \[starting dose\] x 100, \[starting dose\] x 300).

Subjects may continue on treatment following discussion between the Principal Investigator and Sponsor/Medical Monitor.

The Expansion Phase will consist of up to 20 subjects. Subjects will receive intratumoral injections at the RP2D declared at the end of the Dose Escalation Phase of the study. The SRC will define the RP2D for use in the Expansion Phase of the study and may redefine the RP2D during the Expansion Phase based on accumulating safety data.

Eligibility Criteria:
Inclusion Criteria:

1. Age 18+
2. Informed consent
3. Histological or cytopathological confirmed diagnosis of a locally advanced or metastatic solid tumor
4. Progression following at least one prior standard treatment or intolerant of standard treatments.
5. Availability of archival or fresh tumor tissue
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 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. Resolution of any toxicity associated with prior therapy to ≤ Grade 1 (Residual toxicity of Grade 2 may be allowed following discussion with Medical Monitor)
12. Adequate hematologic function defined as:

    1. Absolute neutrophil count \>1,500/uL
    2. Platelet count \>100,000/uL
13. Adequate hepatic function defined as:

    1. Total bilirubin ≤ 1.5 x ULN
    2. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN
14. Adequate coagulation defined as:

    1. International normalized ratio (INR) ≤ 1.5 x ULN or prothrombin time (PT) ≤ 1.5 x ULN
    2. Partial thromboplastin time (PTT) or activated PTT (aPTT) ≤ 1.5 x ULN
15. Serum creatinine ≤ 1.5 x ULN or estimated GFR ≥ 60 mL/min/1.73 m2 (per MDRD GFR formula)
16. Women of childbearing potential must have a negative serum pregnancy test
17. 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. ≤ 21 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. Severe infection requiring systemic antibiotic therapy or hospitalization for treatment of injection within 2 weeks of the first injection of VAX014
5. Need for systemic immunosuppressive therapy (≤10mg of prednisone equivalent, or one time pulse steroids excepted)
6. 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)
7. Known active Hepatitis B or C
8. Women who are pregnant or lactating
9. Clinically significant cardiovascular abnormalities including:

   1. ≤ 12 months from prior MI
   2. Unstable angina pectoris
   3. ≤ 6 months from NYHA classification \>3 CHF
10. Medical or psychological condition that places the subject at undue risk with study participation