BACKGROUND Novel approaches are required to improve outcomes in relapsed or refractory classical Hodgkin lymphoma and non-Hodgkin lymphoma. We aimed to evaluate camidanlumab tesirine, an anti-CD25 antibody-drug conjugate, in this patient population. METHODS This was a phase 1, dose-escalation (part 1), dose-expansion (part 2), multicentre trial done in 12 hospital sites (seven in the USA and five in the UK). Adults (≥18 years old) with pathologically confirmed relapsed or refractory classical Hodgkin lymphoma or non-Hodgkin lymphoma, an Eastern Cooperative Oncology Group performance status 0-2, who had no therapies available to them with established clinical benefit for their disease stage were enrolled. Camidanlumab tesirine was administered intravenously (3-150 μg/kg) once every 3 weeks. Primary objectives were to assess dose-limiting toxicity, determine maximum tolerated dose and recommended expansion dose(s), and assess safety of camidanlumab tesirine. Safety was assessed in all treated patients; antitumour activity was assessed in patients with one or more valid baseline and post-baseline disease assessment and in those who had disease progression or died after first study-drug dose. This trial was registered with ClinicalTrials.gov, NCT02432235. FINDINGS Between Oct 5, 2015, and Jun 30, 2019, 133 patients were enrolled (77 [58%] had classical Hodgkin lymphoma and 56 (42%) had non-Hodgkin lymphoma). Median follow-up was 9·2 months (IQR 4·2-14·3). Eight dose-limiting toxicities were reported in five (6%) of 86 patients who were evaluable; the maximum tolerated dose was not reached. The recommended doses for expansion were 30 μg/kg and 45 μg/kg for patients with classical Hodgkin lymphoma and 80 μg/kg for patients with T-cell non-Hodgkin lymphomas. No recommended doses for expansion were defined for B-cell non-Hodgkin lymphomas. Grade 3 or worse treatment-emergent adverse events (reported by ≥10% of the 133 patients) included increased γ-glutamyltransferase (20 [15%] patients), maculopapular rash (16 [12%]), and anaemia (15 [11%]); 74 (56%) patients had serious treatment-emergent adverse events, most commonly pyrexia (16 [12%]). One (1%) fatal treatment-emergent adverse event and two (2%) deaths outside the reporting period were considered at least possibly study-drug related. Antitumoural activity was seen in classical Hodgkin and non-Hodgkin lymphomas; notably in all patients with classical Hodgkin lymphoma, the overall response was 71% (95% CI 60-81). INTERPRETATION These results warrant evaluation of camidanlumab tesirine as a potential treatment option for relapsed or refractory lymphoma, particularly in patients with classical Hodgkin lymphoma. FUNDING ADC Therapeutics.

中文翻译：

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Camidanlumab tesirine 用于复发或难治性淋巴瘤患者：1 期、开放标签、多中心、剂量递增、剂量扩展研究。

背景技术需要新的方法来改善复发性或难治性经典霍奇金淋巴瘤和非霍奇金淋巴瘤的结果。我们旨在评估该患者群体中的抗 CD25 抗体-药物偶联物 camidanlumab tesirine。方法 这是一项 1 期、剂量递增（第 1 部分）、剂量扩展（第 2 部分）、在 12 个医院（美国 7 个，英国 5 个）进行的多中心试验。招募了经病理证实为复发或难治性经典霍奇金淋巴瘤或非霍奇金淋巴瘤、东部肿瘤协作组体能状态为 0-2 且没有可用疗法对其疾病阶段具有既定临床益处的成人（≥18 岁） . Camidanlumab tesirine 每 3 周静脉内给药一次 (3-150 μg/kg)。主要目标是评估剂量限制毒性，确定最大耐受剂量和推荐的扩展剂量，并评估 camidanlumab tesirine 的安全性。在所有接受治疗的患者中评估了安全性；在具有一个或多个有效基线和基线后疾病评估的患者以及在首次研究药物剂量后疾病进展或死亡的患者中评估抗肿瘤活性。该试验已在 ClinicalTrials.gov 注册，NCT02432235。结果 在 2015 年 10 月 5 日至 2019 年 6 月 30 日期间，共招募了 133 名患者（77 名 [58%] 患有经典霍奇金淋巴瘤，56 名（42%）患有非霍奇金淋巴瘤）。中位随访时间为 9·2 个月（IQR 4·2-14·3）。在可评估的 86 名患者中，有 5 名（6%）报告了 8 种剂量限制性毒性；未达到最大耐受剂量。对于经典霍奇金淋巴瘤患者，扩增的推荐剂量为 30 μg/kg 和 45 μg/kg，对于 T 细胞非霍奇金淋巴瘤患者，推荐剂量为 80 μg/kg。没有为 B 细胞非霍奇金淋巴瘤定义推荐的扩增剂量。3 级或更严重的治疗出现的不良事件（133 名患者中≥10% 报告）包括 γ-谷氨酰转移酶升高（20 [15%] 患者）、斑丘疹（16 [12%]）和贫血（15 [11 %]); 74 名 (56%) 患者出现严重的治疗中出现的不良事件，最常见的是发热 (16 [12%])。报告期之外的一例 (1%) 致命的治疗出现的不良事件和两例 (2%) 的死亡被认为至少可能与研究药物有关。在经典霍奇金淋巴瘤和非霍奇金淋巴瘤中观察到抗肿瘤活性；尤其是在所有经典霍奇金淋巴瘤患者中，总体反应率为 71% (95% CI 60-81)。解释 这些结果值得评估 camidanlumab tesirine 作为复发或难治性淋巴瘤的潜在治疗选择，特别是在经典霍奇金淋巴瘤患者中。资助 ADC 疗法。