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

Inclusion criteria

• Informed consent
• Histological or cytopathological confirmed diagnosis of a locally advanced or metastatic solid tumor
• Progression following at least one prior standard treatment or intolerant of standard treatments.
• \[Dose Escalation\] Availability of archival or fresh tumor tissue
• \[Expansion\] 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)
• No available SOC therapy that would confer clinical benefit
• \[Dose escalation\] 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
• \[Expansion\] At least one injectable tumor (\>=0.5cm in largest diameter) that can be injected either with or without the need for interventional radiology
• \[Expansion\] Appropriate for treatment with either nivolumab or pembrolizumab
• \[Expansion\] Progression following at least one prior regimen containing PD-1 directed immune checkpoint blockade
• Measurable disease by RECIST v1.1
• ECOG Performance Status of 0, 1, or 2
• Resolution of any toxicity associated with prior therapy to ≤ Grade 1 (Residual toxicity of Grade 2 may be allowed following discussion with Medical Monitor)
• Adequate hematologic function defined as:
• Absolute neutrophil count \>=1,500/uL
• Platelet count \>=100,000/uL
• \[Expansion\] Hemoglobin \>=9 gm/dL
• Adequate hepatic function defined as:
• Total bilirubin ≤ 1.5 x ULN
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN
• Adequate coagulation defined as:
• International normalized ratio (INR) ≤ 1.5 x ULN or prothrombin time (PT) ≤ 1.5 x ULN
• Partial thromboplastin time (PTT) or activated PTT (aPTT) ≤ 1.5 x ULN
• Serum creatinine ≤ 1.5 x ULN or estimated GFR ≥ 60 mL/min/1.73 m2 (per MDRD GFR formula)
• Women of childbearing potential must have a negative serum pregnancy test
• 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

• 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
• ≤ 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
• Known CNS metastases or leptomeningeal carcinomatosis, unless adequately treated and clinically stable off steroids for ≥ 14 days from the first injection of VAX014
• Severe infection requiring systemic antibiotic therapy or hospitalization for treatment of injection
• Need for systemic immunosuppressive therapy (≤10 mg of prednisone equivalent, or one time pulse steroids excepted)
• Active autoimmune disease requiring systemic immunosuppressive therapy
• Active lung disease or pneumonitis
• History of Grade 4 toxicity in response to prior PD-1 blockade
• 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)
• Known active infection with tuberculosis or HIV
• Active Hepatitis B or C
• \[Females\] pregnant or breastfeeding
• Clinically significant cardiovascular abnormalities including:
• ≤ 12 months from prior MI
• Unstable angina pectoris
• ≤ 6 months from NYHA classification \>=3 CHF
• 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)
• Medical or psychological condition that places the subject at undue risk with study participation