A Feasibility Study Utilizing Immune Recall to Increase Response to Checkpoint Therapy (TdVax)

The purpose of this study is to determine the safety and feasibility of administering the Tetanus Diptheria Vaccine (Td) or Polio Boost Immunization (IPOL) to patients with metastatic melanoma who are receiving immune checkpoint inhibitor (IO) therapy per standard of care. Subjects will have the vaccine at cycle 4 of IO therapy and will have research blood and tissue samples collected prior to starting IO therapy, at cycle 4 prior to vaccine administration, and at 12-17 days post vaccine.

Study Overview

• Status: Recruiting
• Conditions: Melanoma
• Intervention / Treatment: Biological: Tetanus Diptheria Vaccine; Biological: Polio Boost Immunization

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Carol Ann Wiggs, BSN; Phone Number: 919-684-0281; Email: carolann.wiggs@duke.edu

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
      • Contact: Carol Ann Wiggs, BSN; Phone Number: 919-684-0281; Email: carolann.wiggs@duke.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed advanced metastatic melanoma
2. Male or female participants who are at least 18 years of age on the day of signing informed consent
3. Participants must be planned or scheduled by their treating physician to receive PD-1 therapy or PD-1 plus anti CTLA-4 therapy as standard of care
4. Participant (or legally acceptable representative if applicable) provides written informed consent for the trial
5. Participant must have at least 1 lesion that is at least 8 mm in size and is cutaneous, subcutaneous, palpable, or amenable to ultrasound guided core biopsy. The lesion chosen for biopsy can also be a target lesion but does not have to be a target lesion

6. Adequate organ function as defined below. Standard of care labs drawn within 45 days prior to consent may be used for the purposes of determining eligibility

   1. ANC >/= 1500/uL
   2. platelets >/=100,000/uL
   3. Hemoglobin >/= 9.0 g/dL

Exclusion Criteria:

1. Uveal or mucosal melanoma
2. Any women known to be pregnant or breastfeeding
3. Any prior systemic therapy for metastatic melanoma (prior surgery is allowed)
4. Known diagnosis of immunodeficiency or receiving chronic systemic steroid therapy (in doses exceeding 10 mg daily of prednisone or equivalent), or any other form of immunosuppressive therapy within 7 days prior to first research biopsy

5. Patients with symptomatic CNS metastases and/or carcinomatous meningitis

   a) Patients with asymptomatic, stable CNS metastases are allowed provided that they are not on >10mg prednisone daily

6. History of or active (non-infectious) pneumonitis that required steroids
7. Active infection requiring systemic therapy
8. Known history of Human Immunodeficiency Virus (HIV) infection
9. Known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. NOTE: no testing for Hepatitis B or Hepatitis C is required
10. Known history of active TB (Bacillus Tuberculosis)
11. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with subject's participation for the full duration of the study, or make it not in the best interest of the subject to participate, in the opinion of the treating physician
12. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
13. History of allogenic tissue or solid organ transplant
14. History of allergic reaction to IPOL or Td vaccine
15. Receipt of Td vaccine within 30 days prior to starting IO therapy

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: Td Vaccine; The first 15 subjects enrolled will receive the Td (tetanus diphtheria) vaccine at cycle 4 of IO therapy. The Td vaccine is administered as 0.5 mL intramuscular injection in the extremity (thigh or upper arm) in closest proximity to the largest tumor.	Biological: Tetanus Diptheria Vaccine; tetanus and diphtheria toxoids; Other Names: Tenivac
Experimental: IPOL Vaccine; Subjects 16 through 25 will receive the IPOL (polio booster) vaccine at cycle 4 of IO therapy. The IPOL vaccine is administered as 0.5 mL intramuscular or subcutaneous injection in the extremity (thigh or upper arm) in closest proximity to the largest tumor	Biological: Polio Boost Immunization; trivalent inactivated polio vaccine; Other Names: IPOL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects out of the proposed 25 that successfully receive the vaccine after 4 cycles of IO therapy	Evaluable patients are defined as those who receive four cycles of IO therapy and then receive a Td or IPOL vaccine	informed consent through date of vaccine (est apx 4-5 months)
Safety, as measured by the change in the number and severity of adverse events deemed related to the vaccine or study procedures (blood draw and biopsies)	Adverse events will only include those that are determined to be related to the study vaccine or study procedures (blood draw and biopsies)	Baseline, cycle 4 of IO therapy (apx 12-16 weeks), 12-17 days post vaccine, SOC scan following vaccine (apx 8-12 weeks post vaccine)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preliminary efficacy, as measured by objective response rate	Number of patients that experience tumor response vs. stable disease vs. progression as determined by PI assessment of standard of care scans	up to 36 months

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Georgia Beasley, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2021
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: September 13, 2021
• First Submitted That Met QC Criteria: September 30, 2021
• First Posted (Actual): October 14, 2021

Study Record Updates

• Last Update Posted (Estimated): August 27, 2025
• Last Update Submitted That Met QC Criteria: August 26, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Melanoma; Biological Products; Complex Mixtures; Bacterial Vaccines; Vaccines; Diphtheria Toxoid; Toxoids; Tetanus Toxoid; Vaccines, Combined; Diphtheria-Tetanus Vaccine
• Other Study ID Numbers: Pro00108367

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will only be used internally by the study team

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.: Yes