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卡瑞利珠单抗联合法米替尼治疗铂耐药复发性卵巢癌患者的抗肿瘤活性和安全性:一项开放标签、多中心、2 期篮子研究的结果。

Antitumor activity and safety of camrelizumab plus famitinib in patients with platinum-resistant recurrent ovarian cancer: results from an open-label, multicenter phase 2 basket study.

机构信息

Department of Gynecological Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

Department of Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

出版信息

J Immunother Cancer. 2022 Jan;10(1). doi: 10.1136/jitc-2021-003831.


DOI:10.1136/jitc-2021-003831
PMID:35017154
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8753451/
Abstract

BACKGROUND: Combination treatments with immune-checkpoint inhibitor and antiangiogenic therapy have the potential for synergistic activity through modulation of the microenvironment and represent a notable therapeutic strategy in recurrent ovarian cancer (ROC). We report the results of camrelizumab (an anti-programmed cell death protein-1 antibody) in combination with famitinib (a receptor tyrosine kinase inhibitor) for the treatment of platinum-resistant ROC from an open-label, multicenter, phase 2 basket trial. METHODS: Eligible patients with platinum-resistant ROC were enrolled to receive camrelizumab (200 mg every 3 weeks by intravenous infusion) and oral famitinib (20 mg once daily). All patients had disease progression during or <6 months after their most recent platinum-based chemotherapy. Primary endpoint was confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1 based on investigator's assessment. Secondary endpoints included disease control rate (DCR), duration of response (DoR), time to response (TTR), progression-free survival (PFS), overall survival (OS), 12-month OS rate and safety profile. RESULTS: Of the 37 women enrolled, 11 (29.7%) patients had primary platinum resistant, 15 (40.5%) patients had secondary platinum resistant and 11 (29.7%) patients had primary platinum refractory disease. As the cut-off date of April 9, 2021, nine (24.3%) patients had achieved a confirmed objective response, the ORR was 24.3% (95% CI, 11.8 to 41.2) and the DCR was 54.1% (95% CI, 36.9 to 70.5). Patients with this combination regimen showed a median TTR of 2.1 months (range, 1.8-4.1) and a median DoR of 4.1 months (95% CI, 1.9 to 6.3). Median PFS was 4.1 months (95% CI, 2.1 to 5.7), and median OS was 18.9 months (95% CI, 10.8 to not reached), with the median follow-up duration of 22.0 months (range, 12.0-23.7). The estimated 12-month OS rate was 67.2% (95% CI, 49.4 to 79.9). The most common ≥grade 3 treatment-related adverse events were hypertension (32.4%), decreased neutrophil count (29.7%) and decreased platelet count (13.5%). One (2.7%) patient died of grade 5 hemorrhage that was judged possibly related to study treatment by investigator. CONCLUSION: The camrelizumab with famitinib combination appeared to show antitumor activity in heavily pretreated patients with platinum-resistant ROC with an acceptable safety profile. This combination might provide a novel alternative treatment strategy in platinum-resistant ROC setting and warranted further exploration. TRIAL REGISTRATION NUMBER: NCT03827837.

摘要

背景:免疫检查点抑制剂联合抗血管生成治疗具有通过调节微环境产生协同作用的潜力,是复发性卵巢癌(ROC)的一种显著治疗策略。我们报告了卡瑞利珠单抗(一种抗程序性死亡蛋白-1 抗体)联合法米替尼(一种受体酪氨酸激酶抑制剂)治疗铂耐药 ROC 的结果,这是一项开放标签、多中心、2 期篮子试验。

方法:符合条件的铂耐药 ROC 患者入组接受卡瑞利珠单抗(每 3 周静脉输注 200mg)和法米替尼(每日一次口服 20mg)治疗。所有患者在最近一次含铂化疗期间或化疗结束后<6 个月时疾病进展。主要终点是根据研究者评估的实体瘤反应评价标准(RECIST)V.1.1 确认的客观缓解率(ORR)。次要终点包括疾病控制率(DCR)、缓解持续时间(DoR)、反应时间(TTR)、无进展生存期(PFS)、总生存期(OS)、12 个月 OS 率和安全性特征。

结果:37 名女性患者中,11 名(29.7%)患者为原发性铂耐药,15 名(40.5%)患者为继发性铂耐药,11 名(29.7%)患者为原发性铂难治性疾病。截至 2021 年 4 月 9 日,9 名(24.3%)患者达到确认的客观缓解,ORR 为 24.3%(95%CI,11.8 至 41.2),DCR 为 54.1%(95%CI,36.9 至 70.5)。该联合治疗方案患者的中位 TTR 为 2.1 个月(范围,1.8-4.1),中位 DoR 为 4.1 个月(95%CI,1.9 至 6.3)。中位 PFS 为 4.1 个月(95%CI,2.1 至 5.7),中位 OS 为 18.9 个月(95%CI,10.8 至未达到),中位随访时间为 22.0 个月(范围,12.0-23.7)。估计 12 个月 OS 率为 67.2%(95%CI,49.4 至 79.9)。最常见的≥3 级治疗相关不良事件是高血压(32.4%)、中性粒细胞计数减少(29.7%)和血小板计数减少(13.5%)。1 名(2.7%)患者因研究者判断可能与研究治疗相关的 5 级出血而死亡。

结论:卡瑞利珠单抗联合法米替尼在铂耐药 ROC 患者中表现出抗肿瘤活性,安全性可接受。该联合治疗可能为铂耐药 ROC 提供一种新的治疗策略,值得进一步探索。

临床试验注册号:NCT03827837。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2b6/8753451/6a0f3ad38f4e/jitc-2021-003831f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2b6/8753451/fc3ca266e8c0/jitc-2021-003831f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2b6/8753451/0f434eb255ca/jitc-2021-003831f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2b6/8753451/6a0f3ad38f4e/jitc-2021-003831f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2b6/8753451/fc3ca266e8c0/jitc-2021-003831f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2b6/8753451/0f434eb255ca/jitc-2021-003831f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2b6/8753451/6a0f3ad38f4e/jitc-2021-003831f03.jpg

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Camrelizumab plus Famitinib in Patients with Advanced or Metastatic Renal Cell Carcinoma: Data from an Open-label, Multicenter Phase II Basket Study.

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