Study of PAT in Patients With Solid Tumor Cancers

Phase I Study of Peptide Alarm Therapy (PAT) Administered by Intratumoral Injection With a PD-1/PD-L1 Inhibitor in Patients With Solid Tumor Cancers Who Have Failed 1 or More Prior Therapies

This is a single center Phase I study with extension of peptide alarm therapy (PAT) administered by intratumoral (IT) injection during the 1st course of a standard of care intravenous PD-1/PD-L1 inhibitor for the treatment of locally advanced or metastatic solid tumor cancers that has failed to be controlled after one or more prior therapies including a previous PD-1/PD-L1 inhibitor

Study Overview

• Status: Suspended
• Conditions: Solid Tumor; Metastasis
• Intervention / Treatment: Drug: Peptide Alarm Therapy (PAT)

• Study Type: Interventional
• Enrollment (Estimated): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Masonic Cancer Center at University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Must be seropositive for CMV and EBV.
• Must have at least one HLA-A*0201 allele. This screening can be performed after determining CMV and EBV seropositivity is established or, if available, from the results of previous tumor profiling by any CLIA-certified lab (i.e. Caris, FoundationOne).
• 18 years or older at the time of signing the pre-screening consent.
• ECOG Performance Status 0 or 1.
• Adequate organ function within 14 days of study enrollment
• Cardiac: New York Heart Association (NYHA) Functional Classification Class I.
• Pulmonary: oxygen saturation ≥ 90% on room air.

• Time between last dose of prior anti-cancer therapy and Day 1 of this study:

  • Chemotherapy: a minimum of 28 days since last treatment.
  • Targeted therapy, immunotherapy, investigational agents: a minimum of 45 days since last dose (at least 2 months for anti-VEGF)
  • Prior palliative radiotherapy within 7 days of start of study treatment. Participants must have recovered from all radiation-related toxicities (prior irradiation to targeted lesions is not permitted)
• Must have recovered to CTCAE ≤Grade 1 from previous treatment related acute toxicities.
• Persons of childbearing potential or with partners of childbearing potential must be willing to abstain from heterosexual activity or to use a highly effect form of contraception from the time of study enrollment until at least 4 months after the last dose of PD-1/PD-L1 inhibitor.
• Able to understand and provide voluntary written consent prior to the performance of any research related activity.

Exclusion Criteria:

• Pregnant or breast feeding.
• Requires therapeutic anticoagulation for which it is deemed unsafe to discontinue anticoagulation for 5 days prior to Cycle 1 through Day 7 of Cycle 1
• Class II or greater New York Heart Association Functional Classification criteria or serious cardiac arrhythmias likely to increase the risk of cardiac complications of therapy (e.g. ventricular tachycardia, frequent ventricular ectopy, or supraventricular tachyarrhythmia requiring chronic therapy)
• Known active CNS metastases
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• Has received a live vaccine within 30 days prior to the first dose of study drug.
• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to study enrollment.
• Prior bone marrow and/or solid organ transplant.
• Has severe hypersensitivity (≥Grade 3) to prior PD-1/PD-L1 and/or any of its excipients.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.
• Known seropositive for HIV or known active Hepatitis B or C infection with detectable viral load by PCR
• Known history of active TB (Bacillus Tuberculosis)
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Has uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, interstitial lung disease, non-infectious pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements in the opinion of the treating investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Peptide Alarm Therapy + Pembrolizumab; Participants receive pembrolizumab 200 mg every 3 weeks (Dose Finding Component) or a disease appropriate PD1/PD-L1 inhibitor (Dose Expansion Component) for 2 treatment courses per standard of care. The first dose of PAT is given on Day 1 and on Day 3 (36 to 48 hours after the 1st PAT dose) A second course of the PD1/PD-L1 inhibitor is given per standard of care on Day 22 (Cycle 2 Day 1).

Drug: Peptide Alarm Therapy (PAT); PAT is given on Day 1 by IT injection after the 1st anti PD-1/PD-L1 infusion and again 36-48 hours later on Day 3.; Other Names: Pembrolizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD) of peptide alarm therapy (PAT)	Use CTCAE v5 criteria to count toxicities per patient including proportions and their 95% confidence intervals will be calculated	End of Treatment (typically at day 43)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	Kaplan-Meier curves will be used to estimate with a 95% confidence interval.	6 Months

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota
• Investigators: Principal Investigator: Melissa Geller, MD, Masonic Cancer Center, Univeristy of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: April 14, 2022
• First Submitted That Met QC Criteria: April 14, 2022
• First Posted (Actual): April 21, 2022

Study Record Updates

• Last Update Posted (Estimated): July 24, 2023
• Last Update Submitted That Met QC Criteria: July 20, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: PAT
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplastic Processes; Neoplasms; Neoplasm Metastasis; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: 2021LS105

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