In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. TPS4171-TPS4171
Abstract:
TPS4171 Background: Chronic stress suppresses the immune system and promotes cancer cell growth. In animal studies, we reported that this is mediated by the beta-adrenergic (BA) pathway. We further showed that concurrently blocking the BA pathway with β-blockers (BB) can improve immune checkpoint inhibitor (ICI) efficacy. Our retrospective data analysis revealed that esophageal cancer (EC) patients taking BB for other non-cancer reasons while receiving chemoradiation had significantly better survival and distant control than those not taking BB. We hypothesized that blocking the effects of adrenergic stress with a commonly used BB, propranolol, will improve response to therapies in EC patients. Methods: This is an open-label, non-randomized, phase 2 study of propranolol combined with pembrolizumab and standard chemotherapy in frontline unresectable/metastatic EGAC. Eligible patients must be treatment-naïve, have adequate organ function, have an ECOG performance status of 0 –1, and be able to swallow and retain oral medication. Patients with Her-2 positive cancer, active autoimmune disease, active HIV, Hepatitis B or C, or a history of non-infectious pneumonitis/interstitial lung disease that requires treatment, are ineligible. Patients who are on BB for various indications are also ineligible. Eligible patients will receive mFOLFOX6 every two weeks in combination with pembrolizumab 400 mg intravenously every six weeks and propranolol 30 mg orally twice daily. The mFOLFOX6 dosing regimen will consist of dl-LV 400 mg/m2 and oxaliplatin 85 mg/m2 followed by bolus 5-FU 400 mg/m2 and a 48-hour infusion of 5-FU 2400 mg/m2. The study will include an initial safety lead-in cohort of six patients. The primary endpoint is the overall response rate (ORR) determined by RECIST 1.1. Secondary endpoints include safety, progression-free survival (PFS), overall survival (OS), and ORR as determined by iRECIST. Correlative studies will assess baseline levels or changes in the levels of biomarkers, like, peripheral T-cell subsets/myeloid-derived suppressor cells (MDSC)/cytokines/ and perceived stress scale PSS/chronotropic effects of exercise with efficacy (ORR, PFS, OS). Assuming a historic ORR of 50% with standard treatment, 37 evaluable pts are needed to show a 20% increase in ORR with our proposed treatment with 80% power at a one-sided significance level of α = 0.1. In stage 1, n1= 23 evaluable pts will be enrolled. If there are 13 or more ORRs, an additional n2= 14 pts will be enrolled in stage 2. If 24 or more ORRs are observed in the total n = 37 evaluable pts, the proposed treatment regimen will be considered promising for further study. The study is currently open to enrollment. Clinical trial information: NCT05651594 .
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2023.41.16_suppl.TPS4171
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2023
detail.hit.zdb_id:
2005181-5
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