Abstract 2379: AptBCis2 plus pemetrexed for lung cancer leptomeningeal carcinomatosis and cancer-associated cachexia

Abstract Introduction: Cancer-associated cachexia (CAC) is a multifactorial syndrome characterized by anorexia and body weight loss. CAC is associated with poor survival outcomes and is common in patients with advanced lung cancer, such as leptomeningeal carcinomatosis (LM). Treatment for lung cancer CAC and LM is challenging, and remains an unmet clinical need worthy of investigation. Aptamers are small synthetic oligonucleotides considered as antibody surrogates for targeted delivery. Here we report a novel aptamer-cisplatin conjugate, AptBCis2, which suppressed tumor progression and restored body weights in the mouse LM models. The effects were even more pronounced when combination regimens with AptBCis2 plus pemetrexed were used. Methods: The aptamer was identified via in vivo SELEX using a lung cancer LM orthotopic mouse model. The aptamer was conjugated with cisplatin to form AptBCis2. The tumor suppressive effects were investigated using mouse models. The AptBCis2 was administered through the tail vein; pemetrexed was injected intraperitoneally, and tumor burden was monitored via In Vivo Imaging System. The plasma and the CSF cisplatin concentrations were measured via Inductively Coupled Plasma Mass Spectrometry. Results: AptBCis2 1 mg/kg (equivalent to cisplatin 0.35 mg/kg) alone or in combination with pemetrexed 100 mg/kg both showed superior tumor suppressive effects than cisplatin 2 mg/kg or pemetrexed 100 mg/kg monotherapy, as well as cisplatin 2 mg/kg plus pemetrexed 100 mg/kg combination therapy in lung cancer LM orthotopic mouse models. The treatments were given on day 2, 3, 5, 7, and 9 post tumor inoculation. On day 14 post tumor inoculation, percent of body weight change was about negative 20% in the cisplatin or cisplatin plus pemetrexed groups, positive 3% in the AptBCis2 group, and positive 20% in the AptBCis2 plus pemetrexed group (n = 8 in each group). The mice were sacrificed at day 14 for biochemical and image studies. Early mortality was observed on day 7 in the pemetrexed group with a negative body weight change of 20%. Conclusion: AptBCis2 in combination with pemetrexed showed not only tumor suppressive effects in lung cancer LM orthotopic mouse models but also restored mouse body weights during the treatment course. The data suggested potential roles of AptBCis2 plus pemetrexed in lung cancer LM and CAC. Citation Format: Emily Pei-Ying Lin, Bo-Tsang Huang. AptBCis2 plus pemetrexed for lung cancer leptomeningeal carcinomatosis and cancer-associated cachexia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2379.