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

Advanced Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05901285
• Other study ID #: VX0120
• Status: Recruiting
• Phase: Phase 1
• Start date: November 2, 2023
• Est. completion date: May 2026

Study information

• Verified date: March 2024
• Source: Vaxiion Therapeutics
• Contact: Kirsten Dorr, MBA
• Phone: 858-630-1959
• Email: kdorr[@]sciquus.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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) followed by a dose expansion at the Recommended Phase 2 Dose (RP2D). 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. 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. The SRC will define the RP2D for use in the Expansion Phase of the study and may redefine the RP2D during the Expansion Phase based on accumulating safety data.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: May 2026
• Est. primary completion date: May 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. Availability of archival or fresh tumor tissue

6. No available SOC therapy that would confer clinical benefit

7. [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

8. [Expansion] At least one injectable tumor (between 1 and 10 cm in largest diameter) that can be injected either with or without the need for interventional radiology

9. Measurable disease by RECIST v1.1

10. ECOG Performance Status of 0, 1, or 2

11. Resolution of any toxicity associated with prior therapy to = Grade 1 (Residual toxicity of Grade 2 may be allowed following discussion with Medical Monitor)

12. Adequate hematologic function defined as:

1. Absolute neutrophil count >1,500/uL

2. Platelet count >100,000/uL

13. Adequate hepatic function defined as:

1. Total bilirubin = 1.5 x ULN

2. Aspartate transaminase (AST) and alanine transaminase (ALT) = 2.5 x ULN

14. 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

15. Serum creatinine = 1.5 x ULN or estimated GFR = 60 mL/min/1.73 m2 (per MDRD GFR formula)

16. Women of childbearing potential must have a negative serum pregnancy test

17. 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 (=10mg of prednisone equivalent, or one time pulse steroids excepted)

6. 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)

7. Known active Hepatitis B or C

8. Women who are pregnant or lactating

9. 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

Related Conditions & MeSH terms

• Advanced Solid Tumor

Intervention

Drug:
• VAX014
Intratumorally administered oncolytic agent comprised of recombinant bacterial minicells. VAX014 is not infectious and is not capable of replication

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Sarah Cannon Research Institute at HealthONE	Denver	Colorado
United States	University of Arizona Cancer Center	Tucson	Arizona
United States	George Washington University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Vaxiion Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Tumor Tissue (immune environment)	Tumor biopsies will be assessed for necrosis and immune changes within the tumor.	up to 8 weeks
Other	Anti-Tumor T Cells	Changes in the number of Anti-Tumor T cells before and after treatment.	Up to 20 weeks
Other	Cytokine levels	Changes in the cytokine levels before and after treatment.	Up to 20 weeks
Other	Type 1 IFN response	Changes in type 1 IFN response before and after treatment.	Up to 20 weeks
Other	STING expression	Predictive value of STING as a biomarker	Baseline
Other	RIG-I expression	Predictive value of RIG-I as a biomarker	Baseline
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	Overall Response Rate	Response rate will be evaluated for tumor lesions that will be assessed through CT MRI.	Up to 20 weeks