VAX014Phase 1 Study of Intratumoral Administration of VAX014 With Expansion in Combination With a Checkpoint Inhibitor in Subjects With Advanced Solid Tumors

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. \[Dose Escalation\] Availability of archival or fresh tumor tissue
6. \[Expansion\] Willing to undergo biopsy of the tumor to be injected prior to the initial VAX014 injection (may provide archival tissue instead if approved by Medical Monitor)
7. No available SOC therapy that would confer clinical benefit
8. \[Dose escalation\] 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
9. \[Expansion\] At least one injectable tumor (>=0.5cm in largest diameter) that can be injected either with or without the need for interventional radiology
10. \[Expansion\] Appropriate for treatment with either nivolumab or pembrolizumab
11. \[Expansion\] Progression following at least one prior regimen containing PD-1 directed immune checkpoint blockade
12. Measurable disease by RECIST v1.1
13. ECOG Performance Status of 0, 1, or 2
14. Resolution of any toxicity associated with prior therapy to ≤ Grade 1 (Residual toxicity of Grade 2 may be allowed following discussion with Medical Monitor)
15. Adequate hematologic function defined as:

1. Absolute neutrophil count >=1,500/uL
2. Platelet count >=100,000/uL
3. \[Expansion\] Hemoglobin >=9 gm/dL
16. Adequate hepatic function defined as:

1. Total bilirubin ≤ 1.5 x ULN
2. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN
17. 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
18. Serum creatinine ≤ 1.5 x ULN or estimated GFR ≥ 60 mL/min/1.73 m2 (per MDRD GFR formula)
19. Women of childbearing potential must have a negative serum pregnancy test
20. 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 or ≤ five half-lives (whichever is shorter) between any prior anticancer therapy (e.g., chemotherapy, immunotherapy, intralesional therapy, irradiation) and the first injection of VAX014
3. Known CNS metastases or leptomeningeal carcinomatosis, unless adequately treated and clinically stable off steroids for ≥ 14 days from the first injection of VAX014
4. Severe infection requiring systemic antibiotic therapy or hospitalization for treatment of injection
5. Need for systemic immunosuppressive therapy (≤10 mg of prednisone equivalent, or one time pulse steroids excepted)
6. Active autoimmune disease requiring systemic immunosuppressive therapy
7. Active lung disease or pneumonitis
8. History of Grade 4 toxicity in response to prior PD-1 blockade
9. 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)
10. Known active infection with tuberculosis or HIV
11. Active Hepatitis B or C
12. \[Females\] pregnant or breastfeeding
13. Clinically significant cardiovascular abnormalities including:

1. ≤ 12 months from prior MI
2. Unstable angina pectoris
3. ≤ 6 months from NYHA classification >=3 CHF
14. Electrocardiogram (ECG) with QTcF > 450 msec (males) and QTcF > 470 msec (females) based on an average of triplicate ECGs (triplicate ECGs performed only if initial QTcF exceeds male/female limits)
15. Medical or psychological condition that places the subject at undue risk with study participation