A Phase 1a/1b Dose Escalation/Expansion Study of the Anti-PD-1 Monoclonal Antibody Nofazinlimab in Chinese Patients with Solid Tumors or Lymphoma.

IF 4.4 3区医学 Q2 ONCOLOGY Targeted Oncology Pub Date : 2024-09-01 Epub Date: 2024-09-04 DOI:10.1007/s11523-024-01091-8

Jifang Gong, Ye Guo, Yanqiao Zhang, Yi Ba, Tong Chen, Wei Li, Caicun Zhou, Mengzhao Wang, Haiyan Yang, Yuhong Zhou, Qiqing Cai, Ziping Wang, Gang Huang, Wei Zhang, Rila Su, Zhongheng Cai, Zenglian Yue, Jinzhou Dou, Peiqi Li, Rachel Wu, Archie N Tse, Lin Shen

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Abstract

Background: Immune checkpoint blockade with anti-programmed cell death 1 (PD-1) antibodies has demonstrated efficacy in multiple tumor types. Nofazinlimab is a humanized rat antibody targeting PD-1. A first-in-human study of nofazinlimab conducted in Australia found no dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) was not reached in the range of 1-10 mg/kg.

Objective: We evaluated nofazinlimab for multiple advanced malignancies in Chinese patients.

Patients and methods: This was a phase 1a/1b, open-label, multicenter, dose-escalation/expansion trial. In phase 1a, patients received an abbreviated dose escalation of nofazinlimab at 60 mg and 200 mg every 3 weeks (Q3W) to determine DLTs and the recommended phase 2 dose (RP2D). In phase 1b, patients received the RP2D (monotherapy/combination) in six arms by tumor type; DLTs were evaluated for nofazinlimab plus lenvatinib in the unresectable hepatocellular carcinoma (uHCC) arm. Safety (continuously monitored in patients who received nofazinlimab) and efficacy (patients with measurable baseline disease) were assessed.

Results: Overall, 107 patients were eligible and received nofazinlimab. In phase 1a, no DLTs were observed; the RP2D was 200mg Q3W. In phase 1b, no DLTs were observed with nofazinlimab plus lenvatinib. The safety profile was consistent with that observed in the first-in-human study (NCT03475251). In phase 1b, 21/88 (23.9%) patients achieved confirmed objective responses, 26 (29.5%) had stable disease, and 9/20 (45.0%) patients with uHCC achieved confirmed objective responses to nofazinlimab plus lenvatinib.

Conclusions: Nofazinlimab was well tolerated in Chinese patients. Preliminary efficacy was encouraging, particularly for nofazinlimab plus lenvatinib in uHCC, which is being studied in an ongoing phase 3 trial.

Clinical trial registration: NCT03809767; registered 18 January 2019.

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抗PD-1单克隆抗体Nofazinlimab在中国实体瘤或淋巴瘤患者中的1a/1b期剂量递增/扩增研究。

背景：使用抗程序性细胞死亡 1（PD-1）抗体进行免疫检查点阻断已在多种肿瘤类型中显示出疗效。Nofazinlimab是一种靶向PD-1的人源化大鼠抗体。在澳大利亚进行的一项关于 nofazinlimab 的首次人体研究发现，该药未出现剂量限制性毒性（DLTs），且在 1-10 mg/kg 的范围内未达到最大耐受剂量（MTD）：我们评估了nofazinlimab治疗中国患者多种晚期恶性肿瘤的疗效：这是一项1a/1b期、开放标签、多中心、剂量递增/扩大试验。在1a期，患者接受nofazinlimab的简短剂量升级治疗，剂量为60毫克和200毫克，每3周一次（Q3W），以确定DLT和推荐的2期剂量（RP2D）。在1b期，患者按肿瘤类型在6个治疗组接受RP2D（单药治疗/联合治疗）；在不可切除肝细胞癌（uHCC）治疗组，对nofazinlimab加仑伐替尼的DLT进行了评估。对安全性（持续监测接受nofazinlimab治疗的患者）和疗效（可测量基线疾病的患者）进行了评估：共有107名患者符合条件并接受了nofazinlimab治疗。在 1a 阶段，未观察到 DLT；RP2D 为 200 毫克 Q3W。在1b阶段，nofazinlimab联合来伐替尼治疗未出现DLT。安全性与首次人体研究（NCT03475251）中观察到的结果一致。在1b期研究中，21/88（23.9%）例患者获得了确证客观应答，26（29.5%）例患者病情稳定，9/20（45.0%）例uHCC患者获得了确证客观应答：结论：中国患者对诺法津单抗的耐受性良好。结论：Nofazinlimab在中国患者中的耐受性良好，初步疗效令人鼓舞，尤其是nofazinlimab联合来伐替尼治疗uHCC的疗效，目前正在进行3期临床试验：临床试验注册：NCT03809767；注册时间：2019年1月18日。

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来源期刊

Targeted Oncology 医学-肿瘤学

CiteScore

8.40

自引率

3.70%

发文量

审稿时长

>12 weeks

期刊介绍： Targeted Oncology addresses physicians and scientists committed to oncology and cancer research by providing a programme of articles on molecularly targeted pharmacotherapy in oncology. The journal includes: Original Research Articles on all aspects of molecularly targeted agents for the treatment of cancer, including immune checkpoint inhibitors and related approaches. Comprehensive narrative Review Articles and shorter Leading Articles discussing relevant clinically established as well as emerging agents and pathways. Current Opinion articles that place interesting areas in perspective. Therapy in Practice articles that provide a guide to the optimum management of a condition and highlight practical, clinically relevant considerations and recommendations. Systematic Reviews that use explicit, systematic methods as outlined by the PRISMA statement. Adis Drug Reviews of the properties and place in therapy of both newer and established targeted drugs in oncology.