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

Eligibility 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
• 117. 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
• 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 (≤10 mg of prednisone equivalent, or one time pulse steroids excepted)
• 6. Active autoimmune disease requiring systemic immunosuppressive therapy
• 7. No active lung disease or pneumonitis
• 8. No 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
• 10. Medical or psychological condition that places the subject at undue risk with study participation