Interim analysis of LANTana: Phase Ib study investigating up-regulation of somatostatin receptor-2 (SSTR2) with the de-methylating agent ASTX727 to allow [177Lu]Lu-DOTA-TATE in metastatic neuroendocrine tumors (NETs)

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Introduction: To be suitable for [177Lu]Lu-DOTA-TATE, SSTR2 must be present on tumor surface as per positive uptake on [68Ga]Ga-DOTA-TATE-PET/CT. SSTR2 promoter methylation reduces SSTR2 expression; this can be reversed using a demethylating agent.

Aim(s): To evaluate if treatment with demethylating agent ASTX727 results in re-expression of SSTR2, as per [68Ga]Ga-DOTA-TATE-PET/CT, allowing [177Lu]Lu-DOTA-TATE treatment.

Materials and methods: Key eligibility: NET diagnosis (Ki-67<55%), no/low uptake on baseline [68Ga]Ga-DOTA-TATE-PET/CT. Following 5 days (d) of oral ASTX727 (35mg decitabine + 100mg cedazuridine), [68Ga]Ga-DOTA-TATE-PET/CT is repeated on d8+2. If there is significant uptake (ie greater than background liver in most lesions), combination ASTX727 on d1-5 + [177Lu]Lu-DOTA-TATE on d8+2 is given 8-weekly for 4 cycles. Endpoints: primary - change in uptake on [68Ga]-DOTA-TATE-PET after 1 cycle of ASTX727; secondary - safety & efficacy.

Conference:

Presenting Author:

Authors: Rzeniewicz K, Ward C, Khan S, Naik M, Qurashi M,

Keywords: neuroendocrine tumor, peptide receptor radionucleotide therapy, methylation, [68Ga]Ga-DOTA-peptide-PET, [177Lu]Lu-DOTA-TATE,