A Feasibility Study Utilizing Immune Recall to Increase Response to Checkpoint Therapy

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
A Feasibility Study Utilizing Immune Recall to Increase Response to Checkpoint Therapy

Conditions
-----------------
Melanoma

Intervention / Treatment
-----------------
* Biological: Tetanus Diptheria Vaccine
* Biological: Polio Boost Immunization


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed advanced metastatic melanoma Male or female participants who are at least 18 years of age on the day of signing informed consent 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 Participant (or legally acceptable representative if applicable) provides written informed consent for the trial 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 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 ANC >/= 1500/uL platelets >/=100,000/uL Hemoglobin >/= 9.0 g/dL Exclusion Criteria: Uveal or mucosal melanoma Any women known to be pregnant or breastfeeding Any prior systemic therapy for metastatic melanoma (prior surgery is allowed) 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 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 History of or active (non-infectious) pneumonitis that required steroids Active infection requiring systemic therapy Known history of Human Immunodeficiency Virus (HIV) infection 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 Known history of active TB (Bacillus Tuberculosis) 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 Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial History of allogenic tissue or solid organ transplant History of allergic reaction to IPOL or Td vaccine Receipt of Td vaccine within 30 days prior to starting IO therapy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Td Vaccine<br>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<br>* tetanus and diphtheria toxoids<br>* Other names: Tenivac;|
| Experimental: IPOL Vaccine<br>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<br>* trivalent inactivated polio vaccine<br>* 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 |