Famitinib with Camrelizumab and Nab-Paclitaxel for Advanced Immunomodulatory Triple-Negative Breast Cancer (FUTURE-C-Plus): An Open-Label, Single-Arm, Phase II Trial.
Famitinib with Camrelizumab and Nab-Paclitaxel for Advanced Immunomodulatory Triple-Negative Breast Cancer (FUTURE-C-Plus): An Open-Label, Single-Arm, Phase II Trial.
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Famitinib联合Camrelizumab和nab -紫杉醇治疗晚期免疫调节三阴性乳腺癌（FUTURE-C-Plus）：一项开放标签、单组、II期试验
DOI：
10.1158/1078-0432.ccr-21-4313
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发表时间：
2022-07-01
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Camrelizumab是一种针对程序性细胞死亡蛋白1 （PD-1）的单抗，联合nab-紫杉醇在难治性转移性免疫调节三阴性乳腺癌（TNBC）中显示出有希望的抗肿瘤活性。Famitinib是一种酪氨酸激酶抑制剂，靶向VEGFR2、PDGFR和c-kit。我们旨在评估famitinib、camrelizumab和nab-紫杉醇联合治疗晚期免疫调调性TNBC的有效性和安全性。这项开放标签、单臂、II期研究纳入了先前未经治疗的晚期免疫调节性TNBC （CD8 IHC染色≥10%）患者。符合条件的患者在第1至28天口服famitinib 20 mg，在第1天和第15天静脉注射camrelizumab 200 mg，在第1、8和15天静脉注射nab-紫杉醇100 mg/m2，以4周为周期。主要终点是客观缓解率（ORR），由研究人员根据RECIST v1.1评估。关键的次要终点是无进展生存期（PFS）、总生存期（OS）、反应持续时间（DOR）、安全性和探索性生物标志物。48名患者入组并接受治疗。中位随访时间为17.0个月（范围8.7-24.3）。确诊ORR为81.3%[95%可信区间（CI）， 70.2-92.3]， 5例完全缓解，34例部分缓解。中位PFS为13.6个月（95% CI, 8.4-18.8），中位DOR为14.9个月[95% CI，不可估计(NE) -NE]。中位OS未达到。没有与治疗相关的死亡报告。在30例IHC患者中，13例（43.3%）为程序性死亡配体1 （PD-L1）阴性，PD-L1与良好的应答相关。PKD1和KAT6A体细胞突变与治疗反应相关。三联疗法对先前未治疗的晚期免疫调节性TNBC有效且耐受性良好。随机对照FUTURE-SUPER试验正在进行中，以验证我们的发现。见Salgado和Loi的相关评论，第2728页
Camrelizumab, an mAb against programmed cell death protein 1 (PD-1), plus nab-paclitaxel exhibited promising antitumor activity in refractory metastatic immunomodulatory triple-negative breast cancer (TNBC). Famitinib is a tyrosine kinase inhibitor targeting VEGFR2, PDGFR, and c-kit. We aimed to assess the efficacy and safety of a novel combination of famitinib, camrelizumab, and nab-paclitaxel in advanced immunomodulatory TNBC. This open-label, single-arm, phase II study enrolled patients with previously untreated, advanced, immunomodulatory TNBC (CD8 IHC staining ≥10%). Eligible patients received 20 mg of oral famitinib on days 1 to 28, 200 mg of i.v. camrelizumab on days 1 and 15, and i.v. nab-paclitaxel 100 mg/m2 on days 1, 8, and 15 in 4-week cycles. The primary endpoint was objective response rate (ORR), as assessed by investigators per RECIST v1.1. Key secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response (DOR), safety, and exploratory biomarkers. Forty-eight patients were enrolled and treated. Median follow-up was 17.0 months (range, 8.7–24.3). Confirmed ORR was 81.3% [95% confidence interval (CI), 70.2–92.3], with five complete and 34 partial responses. Median PFS was 13.6 months (95% CI, 8.4–18.8), and median DOR was 14.9 months [95% CI, not estimable (NE)–NE]. Median OS was not reached. No treatment-related deaths were reported. Among 30 patients with IHC, 13 (43.3%) were programmed death-ligand 1 (PD-L1)–negative, and PD-L1 was associated with favorable response. PKD1 and KAT6A somatic mutations were associated with therapy response. The triplet regimen was efficacious and well tolerated in previously untreated, advanced, immunomodulatory TNBC. The randomized controlled FUTURE-SUPER trial is under way to validate our findings. See related commentary by Salgado and Loi, p. 2728