一项评估 BTH1677 联合贝伐珠单抗、卡铂和紫杉醇一线治疗晚期非小细胞肺癌的疗效和安全性的随机、对照试验。

A randomized, controlled trial evaluating the efficacy and safety of BTH1677 in combination with bevacizumab, carboplatin, and paclitaxel in first-line treatment of advanced non-small cell lung cancer.

机构信息

Kliniken der Stadt Köln gGmbH, Krankenhaus Merheim, Thoraxchirurgische u. Pneumologische Klinik, Ostmerheimer Str. 200, 51109, Köln, Germany.

Biothera Pharmaceuticals, Inc., 3388 Mike Collins Drive, Suite A, Eagan, MN, 55121, USA.

出版信息

J Immunother Cancer. 2018 Feb 27;6(1):16. doi: 10.1186/s40425-018-0324-z.

BACKGROUND

BTH1677, a beta-glucan pathogen-associated molecular pattern molecule, drives an anti-cancer immune response in combination with oncology antibody therapies. This phase II study explored the efficacy, pharmacokinetics (PK), and safety of BTH1677 combined with bevacizumab/carboplatin/paclitaxel in patients with untreated advanced non-small cell lung cancer (NSCLC).

METHODS

Patients were randomized to the BTH1677 arm (N = 61; intravenous [IV] BTH1677, 4 mg/kg, weekly; IV bevacizumab, 15 mg/kg, once each 3-week cycle [Q3W]; IV carboplatin, 6 mg/mL/min Calvert formula area-under-the-curve, Q3W; and IV paclitaxel, 200 mg/m, Q3W) or Control arm (N = 31; bevacizumab/carboplatin/paclitaxel as above). Carboplatin/paclitaxel was discontinued after 4-6 cycles and patients who responded or remained stable received maintenance therapy with BTH1677/bevacizumab (BTH1677 arm) or bevacizumab (Control arm). Efficacy assessments, based on blinded central radiology review, included objective response rate (ORR; primary endpoint), disease control rate, duration of objective response, and progression-free survival. Overall survival and adverse events (AEs) were also assessed.

RESULTS

ORR was higher in the BTH1677 vs Control arm but the difference between groups was not statistically significant (60.4% vs 43.5%; P = .2096). All other clinical endpoints also favored the BTH1677 arm but none statistically differed between arms. PK was consistent with previous studies. Although a higher incidence of Grade 3/4 AEs occurred in the BTH1677 vs Control arm (93.2% vs 66.7%), no unexpected AEs were observed. Serious AEs and discontinuations due to AEs were lower in the BTH1677 vs Control arm.

CONCLUSIONS

Improvements in tumor assessments and survival were observed with BTH1677/bevacizumab/carboplatin/paclitaxel compared with control treatment in patients with advanced NSCLC.

TRIAL REGISTRATION

ClinicalTrials.gov registration ID: NCT00874107 . Registered 2 April 2009. First participant was enrolled on 29 September 2009.

背景

BTH1677 是一种β-葡聚糖病原体相关分子模式分子，与肿瘤抗体疗法联合使用可引发抗癌免疫反应。这项 II 期研究探索了未经治疗的晚期非小细胞肺癌（NSCLC）患者中 BTH1677 联合贝伐珠单抗/卡铂/紫杉醇的疗效、药代动力学（PK）和安全性。

方法

患者被随机分配到 BTH1677 组（N=61；静脉内[IV]BTH1677，4mg/kg，每周一次；IV 贝伐珠单抗，15mg/kg，每 3 周周期一次[Q3W]；IV 卡铂，6mg/mL/min 卡尔弗特公式 AUC，Q3W；和 IV 紫杉醇，200mg/m，Q3W）或对照组（N=31；贝伐珠单抗/卡铂/紫杉醇如上所述）。在 4-6 个周期后停止卡铂/紫杉醇治疗，对有反应或稳定的患者接受 BTH1677/贝伐珠单抗（BTH1677 组）或贝伐珠单抗（对照组）维持治疗。根据盲法中心放射学审查，疗效评估包括客观缓解率（ORR；主要终点）、疾病控制率、客观缓解持续时间和无进展生存期。还评估了总生存期和不良事件（AE）。

结果

BTH1677 组的 ORR 高于对照组，但两组之间的差异无统计学意义（60.4% vs 43.5%；P=0.2096）。BTH1677 组的所有其他临床终点也都优于对照组，但两组之间均无统计学差异。PK 与先前的研究一致。尽管 BTH1677 组的 3/4 级不良事件发生率高于对照组（93.2% vs 66.7%），但未观察到意外的不良事件。BTH1677 组严重不良事件和因不良事件停药的发生率低于对照组。