In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. TPS2675-TPS2675
Abstract:
TPS2675 Background: Most colon cancer (CC) patients can be treated with upfront curative surgery; however, relapse often occurs and the disease becomes deadly. Neoadjuvant chemotherapy does not jeopardize timing or quality of surgery and enhances relapse-free outcomes in proficient mismatch-repair (pMMR) CC (Morton et al, J Clin Oncol 2023). In the same setting, the use of immune checkpoint inhibitors (ICIs) with a single dose of ipilimumab (Ipi) and two doses of nivolumab (Nivo) proved to be feasible without delaying surgery and resulting in 23% major pathological responses (mPR) (Chalabi et al, ASCO 2022). We have previously shown that high dose vitamin C (HDVitC) triggers tumor infiltration and activation of CD8+ T cells in mouse tumors, enhancing efficacy of ICIs in pMMR CC preclinical models (Magrì et al, Sci Transl Med 2020). Methods: ALFEO is an open-label pilot trial of neoadjuvant CC treatment to test whether HDVitC can enhance the efficacy of ICIs in this setting. Main inclusion criteria are pMMR CC stage cT4N0/TxN1-2/[cM1 liver-limited disease with favorable oncological criteria candidate for upfront surgery on both T and M after multidisciplinary team evaluation] . Patients will receive Nivo i.v. 3 mg/kg D1 and D15, Ipi i.v. 1 mg/kg D 1 and VitC 70 g/ m 2 D1-3 and 15-17. Tumor assessment will be performed at D21-28, followed by surgery within D28. Primary objective is activity of Nivo/Ipi + HDVitC; secondary objective is safety; exploratory objectives are correlation between efficacy and pharmacodynamic including tumor microenvironment changes. Primary endpoint is mPR rate. Considering the proof-of-principle nature of the trial, a design with a boundary for early stopping (both futility/utility and toxicity) and a fixed maximum sample size of 24 patients has been chosen. mPR for the Ipi/Nivo has been set at 23% (H 0 ), while H 1 at 75%. A Bayesian hypothesis test-based design (Zhou et al, Pharm Stat 2021) will be used for decision-making. Su. Clinical trial information: ECTR2022-502101-15-00 .
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2023.41.16_suppl.TPS2675
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2023
detail.hit.zdb_id:
2005181-5
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