Clinical Trial Finder

Inclusion Criteria:

• - 18 to 99 years of age.

• - Histologically confirmed cutaneous melanoma by historical pathology report review, clinical Stage I-III (Cohort #1), or Stage IV (Cohort #2) cutaneous melanoma.

• - At least one, biopsy-proven, palpable melanoma tumor deposit suitable for intralesional injection measuring ≥ 1 cm by digital caliper (with digital photography documentation) or ultrasound (with ultrasound image documentation) - Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.

Exclusion Criteria:

• - Known allergy or intolerance to influenza vaccination.

• - Subjects with condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone/equivalent) or other immunosuppressive medications within 14 days of study drug administration.

• - Active, known or suspected autoimmune disease.

• - Active brain metastasis or leptomeningeal metastasis.

• - Diagnostic biopsy of ocular or mucosal melanoma.

• - Any melanoma therapy within 6 months of enrollment; though prior surgical resection is permitted.

• - Incarcerated patients.

• - Human immunodeficiency virus (HIV) positive patients.

• - Pregnant or lactating patients.

- Patients incapable of independently providing consent

PRIMARY OBJECTIVE:

• I. To evaluate the safety and tolerability and determine the maximum tolerated dose of intralesional (quadrivalent inactivated influenza vaccine (unadjuvanted influenza vaccine) for patients with a) resectable melanoma as monotherapy, and b) metastatic melanoma, concurrent with standard of care (single- or dual-agent) checkpoint inhibition.

SECONDARY OBJECTIVES:

• I. To evaluate tumor dimensions of injected (Cohorts #1-2) and non-injected lesions (Cohort #2 only), by caliper or ultrasound measurement.

(Clinical endpoint)

• II. To determine time to disease progression (local or distant).

(Clinical endpoint)

• III. To evaluate immunohistochemistry density, cells/mm^2: CD4, CD8, PD-L1, PD1, CD56, CD20, CD45RO, FOXP3.

(Tumor-based endpoint)

• IV. To evaluate granzyme B H-score.

(Tumor-based endpoint)

• V. To evaluate NanoString Pan Cancer Immune Profiling Panel.

(Tumor-based endpoint)

• VI. To evaluate tumor-infiltrating lymphocytes: not identified, present (non-brisk), present (brisk), cannot be determined.

(Tumor-based endpoint)

• VII. To evaluate degree of tumor regression (percent).

(Tumor-based endpoint)

• VIII. To evaluate changes in micro ribonucleic acid (microRNA) expression.

(Tumor-based endpoint)

• IX. To evaluate of flow cytometry for T-cell subset evaluation and changes in circulating microRNA.

(Blood draw endpoint) EXPLORATORY OBJECTIVE:

• I. To evaluate the evidence of immunologic activation in blood and tissue specimens.

OUTLINE: This is dose-escalation study. Patients are assigned to 1 of 2 cohorts. COHORT I: Patients receive quadrivalent inactivated influenza vaccine intramuscularly (IM) on day 0 and intratumorally on days 2 and 14 in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery on day 28. COHORT II: Patients receive quadrivalent inactivated influenza vaccine IM on day 0 and intratumorally on days 2, 14, 28, 42, 56, 70, 84, and 98 in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care ipilimumab, nivolumab, pembrolizumab, or Opdualag. After completion of study treatment, patients are followed up for up to 1 year.

Arms

Experimental: Cohort I (resectable Stage I-III melanoma)

Patients receive an influenza vaccine IM on day 0 and intratumorally on days 2 and 14 in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery on day 28.

Experimental: Cohort II (unresectable Stage IV)

Patients receive an influenza vaccine IM on day 0 and intratumorally on days 2, 14, 28, 42, 56, 70, 84, and 98 in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care (single- or dual-agent) ipilimumab, nivolumab, relatlimab, or pembrolizumab.

Interventions

Biological: - Ipilimumab

immune checkpoint inhibitor

Biological: - Nivolumab

immune checkpoint inhibitor

Biological: - Pembrolizumab

immune checkpoint inhibitor

Biological: - Quadrivalent Inactivated Influenza Vaccine

Given IM and intratumorally. For this protocol the U.S. F.D.A recently approved the use of recently expired influenza vaccine (only until new seasonal vaccine is available anticipated Sept 1). Use of expired vaccine will not exceed 4 months past June 30th expiry date (October 30th).

Procedure: - Resection

Undergo surgical resection

Biological: - Nivolumab + Relatlimab

immune checkpoint inhibitor