Phase Ib/II study of imprime PGG and pembrolizumab in patients with previously treated advanced non-small cell lung cancer (NSCLC): BTCRC LUN 15-017.

IF 4 2区医学 Q2 ONCOLOGY Translational lung cancer research Pub Date : 2024-11-30 Epub Date: 2024-11-19 DOI:10.21037/tlcr-24-346

Muhammad Furqan, Jyoti Malhotra, Ardaman Shergill, Li Liu, Sarah L Mott, Mary M Pasquinelli, Alicia Hulbert, Kathleen Kennedy, Lawrence Feldman

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Abstract

Background: Therapeutic strategies to engage anti-tumor innate immunity are still underdeveloped. Imprime PGG (imprime), a pathogen-associated molecular pattern (PAMP), through pattern recognition receptors, successfully illicit a broad-based innate immune response in preclinical models against various cancers. We aimed to study safety and efficacy of imprime in combination with pembrolizumab in advanced stage non-small cell lung cancer (NSCLC).

Methods: We conducted an investigator-initiated, multi-institutional, single-arm, phase Ib/II trial in previously treated, advanced stage NSCLC patients. Primary endpoints were maximum-tolerated dose (MTD) of imprime for the phase Ib, and progression-free survival (PFS) for the phase II study (NCT03003468).

Results: All 33 eligible patients were included in the safety analysis. No dose-limiting toxicity was observed and the imprime dose of 4 mg/kg was determined as the MTD. Thirty patients treated at the MTD (phase Ib, 6; phase II, 24) were included in the efficacy analysis. Median length of follow-up was 10.8 months. Confirmed objective response rate was 10% [95% confidence interval (CI): 2-27%], with one complete and two partial responses. Median PFS was 2.6 months (95% CI: 1.4-7.0), and 6- and 12-month PFS rates were 37% and 17%, respectively. Median overall survival (OS) was 11.1 months, and 6- and 12-month OS rates were 75% and 46%. Univariate analysis was performed to assess the impact of age, sex, race, disease-stage, programmed death-ligand 1 (PD-L1) expression levels, and prior immunotherapy on PFS and OS. Of these, prior immunotherapy negatively influenced OS [hazard ratio (HR): 2.95, 95% CI: 1.21-7.24]. Overall, the combination was safe and tolerable.

Conclusions: The combination of imprime and pembrolizumab is tolerable but did not improve the outcome of advanced stage NSCLC patients who previously progressed on anti-programmed death 1 (PD-1)/PD-L1 immunotherapies. Further investigation is needed to understand the effects of therapeutic PAMPs to mount a strong innate immune response against cancer.

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Ib/II期研究：imprime PGG和pembrolizumab在既往治疗的晚期非小细胞肺癌（NSCLC）患者中的应用：BTCRC LUN 15-017

背景：利用抗肿瘤先天免疫的治疗策略仍不发达。Imprime PGG （Imprime）是一种病原体相关分子模式（PAMP），通过模式识别受体，在临床前模型中成功地引发了广泛的先天免疫反应，以对抗各种癌症。我们旨在研究imprime联合派姆单抗治疗晚期非小细胞肺癌（NSCLC）的安全性和有效性。方法：我们在先前治疗过的晚期NSCLC患者中进行了一项研究者发起的、多机构、单臂、Ib/II期试验。主要终点是Ib期的最大耐受剂量（MTD）和II期研究的无进展生存期（PFS）（NCT03003468）。结果：33例符合条件的患者均纳入安全性分析。未观察到剂量限制性毒性，确定最佳剂量为4 mg/kg。30例患者接受MTD治疗(Ib期，6例；II期，24例)纳入疗效分析。中位随访时间为10.8个月。确认客观反应率为10%[95%可信区间（CI）： 2-27%]，有1例完全反应和2例部分反应。中位PFS为2.6个月（95% CI: 1.4-7.0）， 6个月和12个月PFS率分别为37%和17%。中位总生存期（OS）为11.1个月，6个月和12个月的OS率分别为75%和46%。采用单因素分析评估年龄、性别、种族、疾病分期、程序性死亡配体1 （PD-L1）表达水平和既往免疫治疗对PFS和OS的影响。其中，既往免疫治疗对OS有负面影响[风险比（HR）： 2.95, 95% CI: 1.21-7.24]。总体而言，该组合是安全且可耐受的。结论：imprime和pembrolizumab联合使用是可耐受的，但并没有改善先前在抗程序性死亡1 (PD-1)/PD-L1免疫治疗中进展的晚期NSCLC患者的预后。需要进一步的研究来了解治疗性PAMPs对癌症产生强大的先天免疫反应的作用。

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来源期刊

Translational lung cancer research Medicine-Oncology

CiteScore

7.20

自引率

2.50%

发文量

137

期刊介绍： Translational Lung Cancer Research(TLCR, Transl Lung Cancer Res, Print ISSN 2218-6751; Online ISSN 2226-4477) is an international, peer-reviewed, open-access journal, which was founded in March 2012. TLCR is indexed by PubMed/PubMed Central and the Chemical Abstracts Service (CAS) Databases. It is published quarterly the first year, and published bimonthly since February 2013. It provides practical up-to-date information on prevention, early detection, diagnosis, and treatment of lung cancer. Specific areas of its interest include, but not limited to, multimodality therapy, markers, imaging, tumor biology, pathology, chemoprevention, and technical advances related to lung cancer.