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

Study Overview
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Brief Summary
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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.

Detailed Description
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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 28-days of injections. Subjects will initially receive weekly intratumoral injections for up to 8 weeks. Subjects may continue on treatment following discussion between the Principal Investigator and Sponsor/Medical Monitor. Only tumors that can be injected under direct visualization or palpation will be injected during the Dose Escalation Phase of the study. 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).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. During the Expansion Phase, the SRC will have the option of redefining the RP2D if appropriate based on accumulating safety data.

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

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: VAX014


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18+ Informed consent Diagnosis of solid tumor(s) relapsed or refractory to standard treatments 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) Progression following at least one prior standard treatment or intolerant of standard treatments. 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 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 Measurable disease by RECIST v1.1 ECOG Performance Status of 0, 1, or 2 Adequate hematologic function defined as: Absolute neutrophil count >1,500/uL Platelet count >100,000/uL Adequate hepatic function defined as: Total bilirubin ≤ 1.5 x ULN Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 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 ≤ 28 days from prior anticancer therapy and C1D1 (e.g., chemotherapy, immunotherapy, intralesional therapy, irradiation therapy) Known CNS metastases or leptomeningeal carcinomatosis, unless adequately treated and clinically stable off steroids for ≥ 14 days from C1D1 Known active infection requiring systemic antibiotic therapy Concurrent use of warfarin, heparin, or chronic NSAID(s) use, including aspirin at > 81 mg daily, within 14 days of C1D1 Need for systemic immunosuppressive therapy 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) Requirement for immunosuppressive therapy (i.e., prednisone equivalent of > 10 mg/day) Known immunodeficiency disorder Known active Hepatitis B or C Women who are pregnant or lactating Medical or physiological condition that places the subject at undue risk with study participation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VAX014<br>Dose escalation of VAX014 [recombinant bacterial minicells (rBMCs)] intratumoral injections alone for subjects with solid tumors relapsed and/or refractory to standard treatment and appropriate for injection of a nodal, subcutaneous, or cutaneous tumor via palpation or with the assistance of ultrasound. In dose expansion, injection may be in metastatic tumors with or without the need for interventional radiology. | Drug: VAX014<br>* Intratumorally administered oncolytic agent comprised of recombinant bacterial minicells. VAX014 is not infectious and is not capable of replication<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) of VAX014 | The MTD will be defined as the dose level at which at most one of six patients experiences a dose limiting toxicity (DLT) after 28 days of treatment have occurred, with the next higher dose having at least 2/3 or 2/6 patients experiencing a DLT | up to 28 days | 
| Incidence of Treatment-Emergency Adverse Events (Safety and Tolerability) | Toxicities will be assessed in each subject by tracking the occurrence of graded Adverse Events (AEs). AEs will be graded according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) v5.0 | Through study completion, an average of 20 weeks | 
| Recommended Phase 2 Dose (RP2D) of intratumoral VAX014 | The RP2D will be determined following the determination of the MTD and with agreement by the Safety Review Committee | up to 5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize systemic exposure by evaluating pharmacokinetics of intratumoral VAX014 [systemic PK] | Whole blood will be collected for determination of VAX014 levels. PK data may demonstrate limited exposure or lack of detectable VAX014 in blood. | up to 1 week | 
| Anti-Drug Antibodies (Immunogenicity)[systemic ADA] | The presence or absence of anti-drug antibodies (ADA) in serum will be assessed by assay. | Up to 20 weeks | 
| Overall Response Rate | Response rate will be evaluated for tumor lesions that will be assessed through CT MRI. | Up to 20 weeks |