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

The purpose of this research study is to evaluate the safety, tolerability and activity of VAX014 for intratumoral injections (VAX014) as a single agent as well as in combination with Investigator's choice of nivolumab or pembrolizumab in patients with advanced solid tumors. VAX014 is a targeted oncolytic agent designed to kill tumor cells following intratumoral injection into advanced solid tumors.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor; Advanced Solid Tumors Appropriate for Treatment With Either Nivolumab or Pembrolizumab
• Intervention / Treatment: Drug: VAX014; Combination product: Nivolumab or pembrolizumab

Detailed Description

This study will evaluate the safety and tolerability of VAX014 using a 3+3 dose escalation design to determine a maximum tolerated dose (MTD) or maximum practical dose (MPD) of single agent VAX014. The DLT assessment period will be the initial 21-days of injections. Subjects will receive weekly injections for the initial 8 weeks. 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).

Subjects may continue on treatment following discussion between the Principal Investigator and Sponsor/Medical Monitor.

After the determination of a single agent RP2D by the SRC for single agent intratumoral VAX014, an Expansion Phase will be conducted combining intratumoral VAX014 with Investigator's choice of nivolumab or pembrolizumab. The SRC may adjust the RP2D of VAX014 used during the Expansion Phase based on accumulating safety data.

The Expansion Phase will consist of up to 25 subjects. For the first 3 subjects treated with the combination of VAX014 and either nivolumab or pembrolizumab, the initial 2 doses of intratumoral VAX014 will be reduced by one dose level from the VAX014 RP2D. If the initial 3 subjects are able to escalate to the RP2D for VAX014, all subsequent subjects will then receive VAX014 at the RP2D starting with the first dose of VAX014.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Kirsten Dorr, IMBA; Phone Number: 858-630-1959; Email: kdorr@sciquus.com
• Study Contact Backup: Name: Kate Peters, BA; Phone Number: 619-614-3800; Email: kpeters@sciquus.com

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Recruiting
      • University of Arizona Cancer Center
      • Contact: Spencer Williams; Phone Number: 520-621-1508; Email: spencerwilliams@arizona.edu
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Sarah Cannon Research Institute at HealthONE
      • Contact: General Contact; Phone Number: 720-754-2610; Email: cann.ddudenvergeneral@sarahcannon.com
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20052
      • Recruiting
      • George Washington University
      • Contact: Alyssa Barnett; Phone Number: 202-994-0246; Email: alyssa.barnett@email.gwu.edu
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
      • Contact: DFCI Referral Team; Phone Number: 857-215-0180; Email: dfcicctiexternalreferral@dfci.harvard.edu
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Recruiting
      • Dartmouth Cancer Center
      • Contact: General Contact; Phone Number: (603) 653-3615; Email: cancer.research.nurse@hitchcock.org
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Recruiting
      • Atlantic Health System
      • Contact: Maureen Nowakowski; Phone Number: 973-971-5569; Email: Maureen.nowakowski@atlantichealth.org
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Contact: Cancer Answer Line; Phone Number: 216-444-7923

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VAX014 (Dose Escalation); 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.	Drug: VAX014; Intratumorally administered oncolytic agent comprised of recombinant bacterial minicells. VAX014 is not infectious and is not capable of replication
Experimental: VAX014 in Combination with Either Nivolumab or Pembrolizumab (Dose Expansion); Dose expansion of VAX014 [recombinant bacterial minicells (rBMCs)] intratumoral injections in combination with Investigator's choice of nivolumb or pembrolizumab 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, with the assistance of ultrasound, or interventional radiology.	Drug: VAX014; Intratumorally administered oncolytic agent comprised of recombinant bacterial minicells. VAX014 is not infectious and is not capable of replication; Combination product: Nivolumab or pembrolizumab; VAX014 will be given in combination with Investigator's choice of nivolumab or pembrolizumab.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 21 days of treatment have occurred, with the next higher dose having at least 2/3 or 2/6 patients experiencing a DLT	up to 21 days
Recommended Phase 2 Dose (RP2D) for single agent 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
Acceptable dose of VAX014 in combination with PD-1 Inhibitor	Determine the acceptable dose of VAX014 when used in combination with Investigator's choice of nivolumab or pembrolizumab	3 months
Evaluation of efficacy of VAX014 in combination with either nivolumab or pembrolizumab	Evaluate efficacy including overall response rate (ORR), response of injected tumor(s) of VAX014 in combination with Investigator's choice of nivolumab or pembrolizumab	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize systemic exposure by evaluating pharmacokinetics of intratumoral VAX014 as monotherapy and (if appropriate) in combination with nivolumab or pembrolizumab [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 in patients receiving VAX014 along or in combination with Investigator's choice of nivolumab or pembrolizumab	Up to 20 weeks
Overall Response Rate as VAX014 alone and in combination with either nivolumab or pembrolizumab	Response rate will be evaluated for tumor lesions that will be assessed through CT, MRI, physical exam.	Up to 20 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Tissue (immune environment)	Tumor biopsies will be assessed for necrosis and immune changes within the tumor.	up to 8 weeks
Anti-Tumor T Cells	Changes in the number of Anti-Tumor T cells before and after treatment.	Up to 20 weeks
Cytokine levels	Changes in the cytokine levels before and after treatment.	Up to 20 weeks
Type 1 IFN response	Changes in type 1 IFN response before and after treatment.	Up to 20 weeks
STING expression	Predictive value of STING as a biomarker	Baseline
RIG-I expression	Predictive value of RIG-I as a biomarker	Baseline

Collaborators and Investigators

• Sponsor: Vaxiion Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2023
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: May 24, 2023
• First Submitted That Met QC Criteria: June 2, 2023
• First Posted (Actual): June 13, 2023

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab; pembrolizumab
• Other Study ID Numbers: VX0120

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No