Interim analysis of Lantana: A phase Ib study to investigate epigenetic modification of somatostatin receptor-2 with ASTX727 to improve therapeutic outcome with [177Lu]Lu-DOTA-TATE in patients with metastatic neuroendocrine tumours (NCT05178693)

Karolina Rzeniewicz; Caroline Ward; Sairah Khan; Mitesh Naik; Tara Barwick; Eric Aboayge; Rohini Sharma

doi:10.1530/endoabs.96.OC2

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Endocrine Abstracts (2023) 96 OC2 | DOI: 10.1530/endoabs.96.OC2

UKINETS2023 Oral Communications Section (3 abstracts)

Interim analysis of Lantana: A phase Ib study to investigate epigenetic modification of somatostatin receptor-2 with ASTX727 to improve therapeutic outcome with [177Lu]Lu-DOTA-TATE in patients with metastatic neuroendocrine tumours (NCT05178693)

Karolina Rzeniewicz ¹ , Caroline Ward ¹ , Sairah Khan ² , Mitesh Naik ² , Tara Barwick ² , Eric Aboayge ¹ & Rohini Sharma ¹

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¹Imperial College, London, United Kingdom; ²Imperial College NHS Healthcare Trust, London, United Kingdom

Background: Peptide-receptor-radionuclide-therapy (PRRT) improves progression free survival in metastatic neuroendocrine neoplasia (NEN). To be suitable for PRRT, somatostatin receptor-2 (SSTR2) must be present on tumour site as determined by positive uptake on [68Ga]Ga-DOTA-peptide-PET/CT. LANTana is an ongoing study evaluating whether treatment with the demethylating agent, ASTX727, results in re-expression of SSTR2, as determined by [68Ga]Ga-DOTA-peptide-PET/CT, allowing subsequent PRRT.

Methods: Key eligibility criteria: histological diagnosis of NEN (Ki67<55%). No/low uptake on baseline [68Ga]Ga-DOTA-TATE-PET/CT

Design: Following baseline [68Ga]Ga-DOTA-peptide-PET/CT, patients receive 5 days of ASTX727 (fixed dose 35mg decitabine + 100mg cedazuridine). [68Ga]Ga-DOTA-peptide-PET/CT is repeated on day 8+2. If there is significant uptake as defined as greater-than-liver-in-most-lesions, patients will receive up to further 4 cycles of ASTX727 on days 1-5 followed by PRRT on day 8+2.

Results: As of 06/09/2023 10 patients were enrolled. Most common primary site was lung (n=5), and median Ki67 was 20% (range 1%-39%). Patients had received a median of two prior systemic treatments (range 1-4). 2 patients withdrew consent prior to repeat [68Ga]Ga-DOTA-peptide-PET/CT. Four patients had re-expression of SSTR2 as illustrated by increase expression on [68Ga]Ga-DOTA-peptide-PET/CT following ASTX727, two of whom proceeded to PRRT. Following administration of ASTX727, 28 grade 1 or 2 adverse events (AEs) occurred in four patients, the commonest being nausea. One episode of grade 3 neutropenic sepsis was recorded. No patient discontinued ASTX727 due to AEs.

Conclusion: Use of a demethylating agent to re-express SSTR2 is feasible allowing PRRT in patients who otherwise would not be eligible. The safety profile was manageable, with no unexpected toxicities. The study is ongoing.