Department of Clinical Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University, Guangzhou, 510060, People's Republic of China.
Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Sun Yat-Sen University, Guangzhou, 510060, People's Republic of China.
J Hematol Oncol. 2024 Nov 29;17(1):118. doi: 10.1186/s13045-024-01644-4.
There is an unmet clinical need to enhance the response rate and safety of anti-PD-1/PD-L1-based cancer immunotherapy (IO). Herein, we presented the clinical study of IBI318 (LY3434172), a first-in-class bispecific antibody (bsAb) targeting PD-1 and PD-L1, in patients with advanced tumors.
In this open-label, multicenter Phase Ia/Ib study of IBI318, the Phase Ia involved dose escalation and a safety dose expansion, while the Phase Ib focused on preliminary safety and efficacy evaluation in non-small cell lung cancer (NSCLC) and nasopharyngeal carcinoma (NPC). In Phase Ia, patients with advanced tumors received IBI318 doses ranging from 0.3 to 1200 mg every two weeks (Q2W) to determine the recommended Phase 2 dose (RP2D). In Phase Ib, NSCLC or NPC patients from five cohorts with varying treatment histories received IBI318 at the RP2D. The primary endpoint was safety and the secondary endpoints included efficacy assessed by investigators according to RECIST v1.1, pharmacokinetics, immunogenicity, and pharmacodynamics.
From February 11, 2019, to January 25, 2022, a total of 103 eligible patients were enrolled (Phase Ia, n = 55; Phase Ib, n = 48). The median follow-up was 10.1 months (range 0.7-28.6). The RP2D was determined to be 300 mg Q2W. Treatment-related adverse events (TRAEs) of any grades occurred in 88 patients (85.4%), while 10 patients (9.7%) experienced grade ≥ 3 TRAEs. The objective response rate (ORR) was 15.5% and the disease control rate (DCR) was 49.5% in all patients. In Phase Ib, the confirmed ORR was 45.5% in treatment-naïve NSCLC patients and 30.0% in IO-naïve NPC patients who had failed or were intolerant to platinum-based treatments.
IBI318 demonstrated a favorable safety profile and preliminary efficacy in treatment-naïve NSCLC and IO-naïve NPC patients. Further clinical studies are needed to assess the full therapeutic potential of PD-1/PD-L1 dual inhibition with bsAbs.
提高抗 PD-1/PD-L1 为基础的癌症免疫疗法（IO）的反应率和安全性存在未满足的临床需求。在此，我们报告了靶向 PD-1 和 PD-L1 的首创双特异性抗体（bsAb） IBI318（LY3434172）在晚期肿瘤患者中的临床研究。
在这项 IBI318 的开放标签、多中心的 I 期/Ib 期研究中，I 期包括剂量递增和安全性扩展，而 Ib 期则侧重于非小细胞肺癌（NSCLC）和鼻咽癌（NPC）中的初步安全性和疗效评估。在 I 期，接受过治疗的晚期肿瘤患者每两周（Q2W）接受 0.3 至 1200mg 的 IBI318 剂量，以确定 II 期推荐剂量（RP2D）。在 Ib 期，来自五个不同治疗史队列的 NSCLC 或 NPC 患者接受了 RP2D 的 IBI318 治疗。主要终点为安全性，次要终点包括研究者根据 RECIST v1.1 评估的疗效、药代动力学、免疫原性和药效学。
从 2019 年 2 月 11 日至 2022 年 1 月 25 日，共有 103 名符合条件的患者入组（I 期，n=55；Ib 期，n=48）。中位随访时间为 10.1 个月（范围 0.7-28.6）。确定的 RP2D 为 300mg Q2W。所有患者中，任何等级的治疗相关不良事件（TRAEs）发生在 88 例患者（85.4%），10 例患者（9.7%）发生了等级≥3 的 TRAEs。所有患者的客观缓解率（ORR）为 15.5%，疾病控制率（DCR）为 49.5%。在 Ib 期，初治 NSCLC 患者的确认 ORR 为 45.5%，IO 初治 NPC 患者对铂类治疗失败或不耐受的确认 ORR 为 30.0%。
IBI318 在初治 NSCLC 和 IO 初治 NPC 患者中表现出良好的安全性和初步疗效。需要进一步的临床研究来评估 PD-1/PD-L1 双抑制用 bsAbs 的全部治疗潜力。
