Peptide Alarm Therapy for advanced or metastatic solid tumors

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

The team will try injecting Peptide Alarm Therapy directly into tumors alongside standard IV PD‑1/PD‑L1 drugs for adults whose advanced or metastatic solid tumors progressed after prior treatments, including prior PD‑1/PD‑L1 therapy.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 21 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Masonic Cancer Center, University of Minnesota (other)
• Drugs / interventions: Chemotherapy, immunotherapy, radiation, prednisone
• Locations: 1 site (Minneapolis, Minnesota)
• Trial ID: NCT05338658 on ClinicalTrials.gov

What this trial studies

This is a single‑center Phase I with extension testing intratumoral Peptide Alarm Therapy (PAT) given during the first course of a standard intravenous PD‑1/PD‑L1 inhibitor. PAT is delivered by direct tumor injection in adults with locally advanced or metastatic solid tumors that were not controlled after one or more prior therapies, including a previous PD‑1/PD‑L1 inhibitor. Eligible participants must be CMV and EBV seropositive and carry at least one HLA‑A*0201 allele, have ECOG 0–1, and adequate organ function. The study is conducted at the Masonic Cancer Center, University of Minnesota, and is focused on early safety, tolerability, and informing potential further development.

Who should consider this trial

Good fit: Ideal candidates are adults (≥18) with ECOG 0–1, CMV and EBV seropositive status, at least one HLA‑A*0201 allele, adequate organ function, and locally advanced or metastatic solid tumors that progressed after prior therapies including a PD‑1/PD‑L1 inhibitor.

Not a fit: Patients who are CMV or EBV seronegative, lack HLA‑A*0201, have poorer performance status (ECOG ≥2), significant cardiac or pulmonary compromise, or cannot travel to Minneapolis are unlikely to be eligible or to benefit.

Why it matters

Potential benefit: If successful, the approach could boost local anti‑tumor immunity and help PD‑1/PD‑L1 therapy control tumors that previously did not respond.

How similar studies have performed: Other early‑phase trials of intratumoral immune‑priming agents combined with PD‑1 blockade have shown promising signals, but peptide alarm therapy itself is a novel approach with limited prior clinical data.

Eligibility criteria

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.

Where this trial is running

Minneapolis, Minnesota

• Masonic Cancer Center at University of Minnesota — Minneapolis, Minnesota, United States (RECRUITING)

Study contacts

• Principal investigator: Melissa Geller, MD — Masonic Cancer Center, Univeristy of Minnesota
• Study coordinator: Cancer Center Clinical Trials Office

Conditions: Metastasis, Solid Tumor, PAT