Testing VAX014 injections in patients with advanced solid tumors

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

This study is testing a new injection called VAX014 to see if it can safely help people with advanced solid tumors.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 43 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Vaxiion Therapeutics (industry)
• Drugs / interventions: nivolumab, pembrolizumab, chemotherapy, immunotherapy, prednisone
• Locations: 8 sites (Tucson, Arizona and 7 other locations)
• Trial ID: NCT05901285 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety, tolerability, and activity of VAX014, a targeted oncolytic agent, administered through intratumoral injections in patients with advanced solid tumors. The study employs a 3+3 dose escalation design to identify the maximum tolerated dose (MTD) followed by a dose expansion phase at the recommended phase 2 dose (RP2D). Participants will receive weekly injections for the first 8 weeks, with up to six dose levels assessed. The trial aims to gather data on the drug's safety and efficacy in treating advanced solid tumors.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with histologically confirmed advanced solid tumors that have progressed after standard treatments.

Not a fit: Patients with early-stage tumors or those who have not yet undergone standard treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors who have limited treatment alternatives.

How similar studies have performed: While this approach is novel, similar studies using intratumoral therapies have shown promise in treating various cancers.

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. \[Dose Escalation\] 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

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 (≤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

Where this trial is running

Tucson, Arizona and 7 other locations

• University of Arizona Cancer Center — Tucson, Arizona, United States (RECRUITING)
• Sarah Cannon Research Institute at HealthONE — Denver, Colorado, United States (RECRUITING)
• George Washington University — Washington D.C., District of Columbia, United States (RECRUITING)
• University of Maryland — Baltimore, Maryland, United States (RECRUITING)
• Dana Farber Cancer Institute — Boston, Massachusetts, United States (RECRUITING)
• Dartmouth Cancer Center — Lebanon, New Hampshire, United States (RECRUITING)
• Atlantic Health System — Morristown, New Jersey, United States (RECRUITING)
• Cleveland Clinic — Cleveland, Ohio, United States (RECRUITING)

Study contacts

• Study coordinator: Kirsten Dorr, IMBA

Conditions: Advanced Solid Tumor, Advanced Solid Tumors Appropriate for Treatment With Either Nivolumab or Pembrolizumab