CMP-001 and INCAGN01949 for Patients With Stage IV Pancreatic Cancer and Other Cancers Except Melanoma

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PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose and tolerance of virus-like particle VLP-encapsulated TLR9 agonist CMP-001 (CMP-001 [TLR9 agonist]) in combination with agonistic anti-OX40 monoclonal antibody INCAGN01949 (INCAGN01949) (an activating antibody against OX40) both given in...

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose and tolerance of virus-like particle VLP-encapsulated TLR9 agonist CMP-001 (CMP-001 [TLR9 agonist]) in combination with agonistic anti-OX40 monoclonal antibody INCAGN01949 (INCAGN01949) (an activating antibody against OX40) both given intratumorally for patients with previously treated (for their metastatic disease) pancreatic ductal adenocarcinoma and other types of cancer except melanoma. (Phase IB) II. To determine the efficacy (disease control rate of complete response [CR] + partial response [PR] + stable disease [SD] X 16 weeks) of CMP001 (TLR9 agonist) in combination with INCAGN01949 (anti-OX40 antibody) for patients with previously treated (for their metastatic disease) pancreatic ductal adenocarcinoma. (Phase II) III. To determine effects on tumor markers. (Phase II) SECONDARY OBJECTIVES: I. Define the toxicity of the combination of CMP-001 (TLR9) + INCAGN01949 (OX40). II. Determine progression free survival and overall survival. EXPLORATORY OBJECTIVES: I. Using flow cytometry on peripheral blood OX40 expression will be analyzed within the lymphocyte subsets (effector T cell [Teff] and regulatory T cell [Treg]). II. On tissue samples collected prior to, and during, treatment, will: IIa. Use flow cytometry to enumerate CD4+ and CD8+ T cell subsets, and the expression of activation/differentiation markers (including CD127, HLA-DR, CD45RO, CCR7, CXCR3) on each. IIb. Use reverse transcriptase-polymerase chain reaction (RT-PCR) and sequencing to amplify and characterize the T-cell receptor (TCR)a and b sequences of tumor-infiltrating T cells, looking for evidence of oligoclonal T cell expansion, OX40 expression. IIc. If there is adequate tumor tissue, perform ribonucleic acid sequencing (RNAseq) to determine different immune cell populations, including T cells and macrophages. OUTLINE: This is a phase Ib, dose-escalation study of INCAGN01949, followed by a phase II study. Patients receive CMP-001 subcutaneously (SC) on day 1 of weeks 1 and 2 and intratumorally (IT) on day 1 of weeks 3-6 in the absence of disease progression or unacceptable toxicity. Patients also receive INCAGN01949 IT on day 1 of weeks 3-6 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days, and then every 12 weeks.

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