398 neoIRX: a phase II trial of locoregional cytokine therapy to promote immunologic priming and clinical response to neoadjuvant pembrolizumab plus chemotherapy in triple negative breast cancer (TNBC)
| Autor: | Alison Conlin, William L. Redmond, Staci Mellinger, Sasha E. Stanton, Nicole Moxon, Yaping Wu, Janet Ruzich, Parvin Peddi, David L. Page, Zhaoyu Sun, Katherine Sanchez, Kelly Shea Perlewitz |
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| Rok vydání: | 2021 |
| Předmět: |
Pharmacology
Oncology Cancer Research medicine.medical_specialty Chemotherapy Cyclophosphamide business.industry medicine.medical_treatment Immunology Cancer Pembrolizumab medicine.disease Carboplatin chemistry.chemical_compound chemistry Internal medicine medicine Clinical endpoint Molecular Medicine Immunology and Allergy business Neoadjuvant therapy Triple-negative breast cancer medicine.drug |
| Zdroj: | Journal for ImmunoTherapy of Cancer. 9:A430-A430 |
| ISSN: | 2051-1426 |
| DOI: | 10.1136/jitc-2021-sitc2021.398 |
| Popis: | BackgroundBackground: The FDA has approved pembrolizumab in combination with neoadjuvant chemotherapy (doxorubicin, cyclophosphamide, paclitaxel [ACT], and carboplatin) for stage II/III TNBC, on the basis of improved event free survival (EFS) and pathologic complete response (pCR) rate in the Keynote-522 study.1 Novel combination immunotherapy strategies may further improve outcomes and allow the opportunity to de-escalate the chemotherapy backbone, potentially mitigating grade III/IV toxicities which occurred in 81% of recipients. We have previously reported safety and feasibility of pre-operative IRX-2, a novel cytokine biotherapeutic, that is administered locoregionally in the peri-areolar tissue to enhance the immune microenvironment within the sentinel lymph nodes, the putative site of antigen presentation.2 In this phase Ib study, pre-operative IRX-2 was safe and was associated with increased tumor infiltrating lymphocytes (sTILs, by H&E and multispectral immunofluorescence [mIF]), PD-L1 expression (Ventana SP142 assay, mIF), and lymphocyte activation (by RNA sequencing). Similar effects were observed in a pre-operative head and neck carcinoma trial. These findings support further study of IRX-2 in combination with anti-PD-1 in early stage TNBC.MethodsMethodsneoIRX is an open-label, phase II trial to evaluate the clinical and immunological activity of induction IRX-2 plus pembrolizumab, followed by de-escalated chemotherapy (ACT) and pembrolizumab as neoadjuvant therapy in TNBC. Patients are randomized to receive pembrolizumab induction (single dose 200mg IV, n=15), versus pembrolizumab + IRX-2 induction (1mL SQ x 2 daily, x 10 days, n=15), followed by research biopsy. All patients will then receive neoadjuvant pembrolizumab plus ACT every three 3 weeks. Eligible subjects will have previously untreated, resectable stage II/III TNBC. The primary endpoint is pCR. The secondary endpoint is safety. On-treatment biopsies will permit a prospective, randomized validation of previously reported immunomodulatory effects of IRX-2 (sTILs, PD-L1, lymphocyte RNA signatures). As of 7/28/2021, n=7/30 subjects are enrolled (Providence Cancer Institute, Portland, OR, Providence St. John’s Cancer Institute, Santa Monica, CA, Baylor Medicine, Houston, TX).Trial RegistrationNCT04373031ReferencesSchmid PN. Engl J Med 2020; 382:810–821.Page DB. Clinical Cancer Research 26.7(2020):1595–1605.Ethics ApprovalThe study protocol was approved by the Providence Portland Medical Center IRB committee and was conducted in accordance with the ethical standards established by the Declaration of Helsinki, PH&S IRB# 2019000486. Written informed consent was obtained for all trial participants. |
| Databáze: | OpenAIRE |
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