Stereotactic body radiotherapy plus cadonilimab (PD-1/CTLA-4 bispecific antibody) as third-line or beyond therapy for refractory solid tumors: A phase 1b study

IF 24.9 1区医学 Q1 ONCOLOGY

Cancer Communications Pub Date : 2025-07-22 DOI:10.1002/cac2.70051

Yao Xiao, Yuxia Wang, Jun Li, Cheng Cheng, Chunyong Song, Xin Wang, Liyuan Tao, Hongqing Zhuang

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Abstract

Background

Cadonilimab is a humanized immunoglobulin G1 bispecific antibody targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). This study aimed to evaluate the safety and efficacy of stereotactic body radiotherapy (SBRT) combined with cadonilimab in patients with advanced recurrent or refractory solid tumors.

Methods

Patients with advanced solid tumors who progressed after at least two lines of systemic treatment, including immunotherapy, and were eligible for SBRT were enrolled. SBRT was administered to patients with high-burden/symptomatic lesions in combination with intravenous cadonilimab (6 mg/kg, once every 2 weeks). The primary endpoint was safety.

Results

Sixty-three patients were enrolled from August 28, 2022, to September 14, 2023 (median follow-up: 9.1 months). The median prior treatment line was 3.0 (range 2.0-4.0). Approximately 46.0% (29/63) of patients had received prior PD-1/PD-L1 therapy, 36.5% (23/63) and 12.7% (8/63) of patients had non-small cell lung cancer and soft tissue sarcoma. Treatment-related adverse events (TRAEs) occurred in 38.1% (24/63) of patients, with grade 3 TRAEs reported in 3.2% (2/63). The most common TRAEs included pain (12.7%), elevated transaminases (12.7%), pneumonia (6.4%), fatigue (6.4%), nausea (4.8%), and fever (4.8%). The objective response rate (ORR) was 23.8% (95% confidence interval [CI], 14.0%-36.2%). The median progression-free survival (PFS) was 7.2 months (95% CI, 6.3-8.2 months), and the median overall survival (OS) was 10.0 months (95% CI, 7.7-12.4 months). The 6-month and 12-month local control rates were 98.4% and 93.0%, respectively. In a subgroup analysis of 23 non-small cell lung cancer patients, the ORR was 17.4% (95% CI, 5.0%-38.8%), the median PFS was 6.9 months (95% CI, 4.7-9.1 months), and the median OS was 9.1 months (95% CI, 7.3-10.9 months). Multivariate analysis indicated that receiving ≥6 cycles of cadonilimab and having an Eastern Cooperative Oncology Group performance status score of 0-1 were significantly associated with improved PFS and OS (P < 0.05).

Conclusions

SBRT in combination with cadonilimab demonstrated manageable toxicity and promising efficacy in heavily pretreated patients with refractory solid tumors.

Trial registration

This study was retrospectively registered at ClinicalTrials.gov (NCT05915481) on August 20, 2022.

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立体定向放疗加卡多尼单抗（PD-1/CTLA-4双特异性抗体）作为治疗难治性实体瘤的三线或二线治疗：一项1b期研究

背景：卡多尼利单抗是一种人源化免疫球蛋白G1双特异性抗体，靶向程序性细胞死亡蛋白1 （PD-1）和细胞毒性t淋巴细胞相关抗原4 （CTLA-4）。本研究旨在评价立体定向放射治疗（SBRT）联合卡多尼单抗治疗晚期复发或难治性实体瘤的安全性和有效性。方法：纳入了至少两种系统治疗（包括免疫治疗）后进展的晚期实体瘤患者，并符合SBRT的条件。SBRT联合静脉注射卡多尼单抗（6 mg/kg，每2周1次）给药于高负担/症状性病变患者。主要终点是安全性。结果：从2022年8月28日至2023年9月14日，共入组63例患者（中位随访时间：9.1个月）。先前治疗线的中位数为3.0（范围为2.0-4.0）。约46.0%（29/63）的患者既往接受过PD-1/PD-L1治疗，36.5%（23/63）和12.7%（8/63）的患者患有非小细胞肺癌和软组织肉瘤。治疗相关不良事件（TRAEs）发生率为38.1%(24/63)，3级TRAEs发生率为3.2%（2/63）。最常见的trae包括疼痛（12.7%）、转氨酶升高（12.7%）、肺炎（6.4%）、疲劳（6.4%）、恶心（4.8%）和发烧（4.8%）。客观有效率（ORR）为23.8%（95%可信区间[CI]， 14.0% ~ 36.2%）。中位无进展生存期（PFS）为7.2个月（95% CI, 6.3-8.2个月），中位总生存期（OS）为10.0个月（95% CI, 7.7-12.4个月）。6个月和12个月当地控制率分别为98.4%和93.0%。在23例非小细胞肺癌患者的亚组分析中，ORR为17.4% (95% CI, 5.0%-38.8%)，中位PFS为6.9个月（95% CI, 4.7-9.1个月），中位OS为9.1个月（95% CI, 7.3-10.9个月）。多因素分析显示，接受卡多尼单抗治疗≥6个周期且东部肿瘤合作组绩效状态评分0-1分与PFS和OS改善显著相关（P < 0.05）。结论：SBRT联合卡多尼利单抗在重度预处理的难治性实体瘤患者中显示出可控的毒性和良好的疗效。试验注册：该研究于2022年8月20日在ClinicalTrials.gov （NCT05915481）上回顾性注册。

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来源期刊

Cancer Communications Biochemistry, Genetics and Molecular Biology-Cancer Research

CiteScore

25.50

自引率

4.30%

发文量

153

审稿时长

4 weeks

期刊介绍： Cancer Communications is an open access, peer-reviewed online journal that encompasses basic, clinical, and translational cancer research. The journal welcomes submissions concerning clinical trials, epidemiology, molecular and cellular biology, and genetics.