PO.CL12.02 · 临床研究
OXC-101（karonudib）治疗犬淋巴瘤和血管肉瘤：安全性、早期疗效及转化潜力
OXC-101 (karonudib) in canine lymphoma and hemangiosarcoma: Safety, early efficacy, and translational potential
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：犬淋巴瘤（CL）和血管肉瘤（HSA）是侵袭性恶性肿瘤。目前的治疗疗效有限，且毒性严重，导致患者生活质量（QoL）低下。它们与人非霍奇金淋巴瘤和人血管肉瘤存在很强的生物学和临床相似性，这使得犬成为转化研究中颇具吸引力的模型。OXC-101（Karonudib）是一种双功能MTH1抑制剂，可诱导氧化核苷酸掺入DNA，并抑制微管聚合，从而对癌细胞产生毒性。OXC-101目前正在两项人体临床试验中进行评估（实体瘤1期；血液系统恶性肿瘤1/2期），并已获得急性髓系白血病的孤儿药资格认定，凸显了其转化相关性。
方法：我们开展了一项开放标签的先导研究，以评估口服OXC-101治疗9只患CL（n=6）或HSA（n=3）的宠物犬的安全性和初步疗效。犬每隔一天口服8-10 mg/kg，每日两次，持续最多八个月。通过临床检查、实验室分析和主人反馈来监测安全性、疗效和生活质量。
结果：8只犬（5只CL，3只HSA）完成了可评估部分；2只因与治疗无关的原因退出。入组试验的大多数CL病例在基于阿霉素（Adriamycin）的化疗后出现疾病复发。复发的CL犬表现出从疾病稳定到部分缓解，持续最长达五个月，生活质量改善且无明显毒性。1只初治的V期CL犬在自愿退出前的21天内出现淋巴结迅速缩小和肝酶正常化。在HSA中，3只行脾切除术的犬中有2只在超过150天后仍无复发且生活质量良好。在所有入组患者中，OXC-101均耐受良好，无胃肠道副作用，无中性粒细胞减少/血小板减少或任何显著的生化异常。
结论：本先导研究表明，OXC-101是安全的，并在复发性CL和术后HSA中显示出早期抗肿瘤活性。鉴于这些犬类癌症与其人类对应癌症之间的密切相似性以及正在进行的人体试验，这些结果强有力地支持进一步的临床开发。OXC-101可能代表兽医和人类肿瘤学的一种有前景的新型靶向治疗。
查看英文原文 English abstract
Background: Canine lymphoma (CL) and hemangiosarcoma (HSA) are aggressive malignancies. Current treatments have limited efficacy, profound toxicity which causes poor quality of life (QoL) in patients. There is strong biological and clinical similarity to human non-Hodgkin lymphoma and human angiosarcoma, which makes dogs an attractive model for translation research. OXC-101 (Karonudib), a dual-function MTH1 inhibitor, induces incorporation of oxidized nucleotides into DNA and inhibits microtubule polymerization and includes the toxicity in cancer cells. OXC-101 is currently being evaluated in two human clinical trials (Phase 1 solid tumors; Phase 1/2 hematologic malignancies) and has received Orphan Drug Designation for acute myeloid leukemia, underscoring its translational relevance.
Methods: We conducted an open-label pilot study to assess safety and preliminary efficacy of oral OXC-101 in nine pet dogs with CL (n=6) or HSA (n=3). Dogs received 8-10 mg/kg orally twice daily every other day for up to eight months. Clinical exams, laboratory analyses, and owner feedback were used to monitor safety, response, and quality of life.
Results: Eight dogs (five CL, three HSA) completed the evaluable portion; two withdrew for reasons unrelated to treatment. Most CL cases enrolled to trial had relapsed disease after Adriamycin-based chemotherapy. Relapsed CL dogs showed stable disease to partial responses lasting up to five months, with improved quality of life and no evident toxicity. One treatment-naïve stage V CL dog showed rapid lymph node reduction and normalization of liver enzymes within 21 days before voluntary withdrawal. In HSA, two out of three splenectomised dogs remain recurrence-free beyond 150 days with good QoL. In all the enrolled patients, OXC-101 was found to be well tolerated, with no gastrointestinal side effects, no neutropenia/ Thrombocytopenia or any significant biochemical abnormalities.
Conclusions: This pilot study shows that OXC-101 is safe and demonstrates early antitumor activity in relapsed CL and post-operative HSA. Given the close parallels between these canine cancers and their human counterparts-and ongoing human trials- these results strongly support further clinical development. OXC-101 may represent a promising new targeted therapy for both veterinary and human oncology.
利益披露 Disclosure
K. Sanjiv,
Oxcia Ab Stock.
S. Saelström, None.
M. Scobie,
Oxcia AB Employment, Stock.
U. Berglung,
Oxcia AB Employment, Stock.
T. Helleday,
Oxica AB Stock.
One Carbon Theraputics Stock.
H. Rönnberg, None.