Abstract

Background

This trial is based on a combination strategy with two immunostimulatory agents in the search of synergism that may induce responses with long-term clinical benefit in ABC pts. Safety data from the run-in-phase were published in ESMO IO 2018. Here, we report the results from the phase II part of the study.

Methods

HER2-negative ABC pts previously treated with anthracyclines and taxanes (unless contraindicated), ≤ 4 chemotherapy lines and/or ≥ 2 hormone therapy lines, and irrespective of PD-L1 status, were eligible. Study treatment consisted of 21-day cycles (cy) of P 200mg on day 1 and Gem 1250mg/m² on days 1 and 8 until progressive disease (PD) or unacceptable toxicity, whatever occurred first. Primary objective was Objective Response Rate (ORR).

Results

Thirty-six pts were included in the first stage of a Simon’s design. Recruitment was stopped as only 5 pts presented an objective response (partial) (≥ 7 responses needed to continue recruiting pts). Median age was 52 years (range 31-77), 21 pts had triple negative disease, the majority of pts had an ECOG performance status ≤ 1 (n = 35), visceral involvement (n = 28) and ≥ 2 metastatic locations (n = 27). Median number of prior lines (any therapy) for ABC was 4 (range 0-11). Pts received a median of 4.5 cy of Gem and 4 cy of P (same range for both drugs, 1-24). The median relative dose intensity of P and Gem was 100% and 80%, respectively. Treatment discontinuation due to PD was reported on 29 pts. The ORR was 15.2% (95% confidence interval (CI) 5.1-31.9) and the Clinical Benefit Rate was 17% (95% CI 33.5-69.2); median duration of objective response was 4.3 months (mo) (95% CI 2.3-7.4), median Progression-Free Survival was 3.1 mo (95% CI, 2-4.3), and median Overall Survival was 7.9 mo (95% CI 6.5-10.3). Eight pts were on treatment ≥ 6 mo before PD (2 pts on 11.4 and 16.1 mo). Grade (G) ≥ 3 AEs related to the study treatment were reported on 14 pts (39%), being neutropenia the most common G3 (22.2%) and G4 (5.6%) AE.

Conclusion

P can be safely combined with Gem, the combination did not meet the efficacy objective in terms of ORR but 22.2% pts were on treatment ≥ 6 mo.

Clinical trial identification

NCT03025880.

Legal entity responsible for the study

GEICAM Spanish Breast Cancer Group.

Funding

MSD.

Disclosure

J. Cruz: Honoraria (self), Advisory / Consultancy: Glaxo; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pharmamar; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Pfizer. M. Ramos Vazquez: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer. J. Cortés: Honoraria (self), Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Celgene; Advisory / Consultancy: Cellestia; Honoraria (institution), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Biothera Pharmaceutical; Advisory / Consultancy: Merus; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Daiichi Sankyo; Advisory / Consultancy: Erytech; Advisory / Consultancy: Athenex; Advisory / Consultancy: Polyphor; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (institution), Advisory / Consultancy: Servier; Honoraria (self), Honoraria (institution), Advisory / Consultancy: MSD; Advisory / Consultancy: GSK; Honoraria (self): Novartis; Honoraria (self), Honoraria (institution): Eisai; Honoraria (self), Honoraria (institution): Pfizer; Honoraria (self): Samsung Bioepis; Honoraria (institution), MedSIR (Stock, patent and intellectual property): Ariad Pharmaceuticals. Baxalta GMBH/Servier Affaires. Bayer Healthcare. Guardanth Health. Piqur Therapeutics. Puma C. Queen Mary University of London. Seagen. All other authors have declared no conflicts of interest.

中文翻译：

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102P派姆单抗（P）加吉西他滨（Gem）在HER2阴性晚期乳腺癌（ABC）患者（pts）的II期试验中的结果：GEICAM / 2015-04（PANGEA-Breast）研究

抽象的

背景

该试验基于与两种免疫刺激剂的联合策略，以寻找可能诱导ABC pts具有长期临床获益的协同作用。运行阶段的安全性数据已发布在ESMO IO 2018中。在这里，我们报告了研究的第二阶段部分的结果。

方法

符合条件的是先前用蒽环类和紫杉烷类药物治疗的HER2阴性ABC患者（除非禁忌），≤4种化疗和/或≥2种激素治疗，并且不论PD-L1状态如何。研究治疗包括第21天（cy）的第1天P 200mg和第1天和第8天的Gem 1250mg / m ²周期（cy），直到进行性疾病（PD）或不可接受的毒性为止，无论先发生什么。主要目标是客观回应率（ORR）。

结果

西蒙设计的第一阶段包含了36点。停止招募是因为只有5分表示客观（部分）答复（≥7分才能继续招募pt）。中位年龄为52岁（范围31-77），其中21例患有三重阴性疾病，大多数患者的ECOG表现状态≤1（n = 35），内脏受累（n = 28）和≥2个转移部位（n = 27）。ABC以前的行（任何治疗）的中位数为4（范围为0-11）。Pts的中位数是4.5 cy的Gem和4 cy的P（两种药物的范围相同，为1-24）。P和Gem的中位相对剂量强度分别为100％和80％。据报道有29名患者因PD而终止治疗。ORR为15.2％（95％置信区间（CI）5.1-31.9），临床受益率为17％（95％CI 33.5-69.2）；客观应答的中位数为4.3个月（mo）（95％CI 2.3-7.4），无进展生存的中位数为3.1 mo（95％CI，2-4.3），整体生存的中位数为7.9 mo（95％CI 6.5） -10.3）。PD前≥6 mo接受治疗的有8分（11.4和16.1 mo接受了2分）。据报道，与研究治疗相关的（G）≥3 AE发生在14分（39％）上，其中中性粒细胞减少是最常见的G3（22.2％）和G4（5.6％）AE。

结论

P可以安全地与Gem结合使用，该组合在ORR方面未达到疗效目标，但治疗≥6 mo时有22.2％的患者。

临床试验鉴定

NCT03025880。

负责研究的法人实体

GEICAM西班牙乳腺癌小组。

资金

MSD。

揭露

J. Cruz：Honoraria（个体经营），咨询/顾问：葛兰素；Honoraria（个体经营），咨询/顾问：AstraZeneca；酬金（个体经营），咨询/顾问：Roche；Honoraria（个体经营），咨询/顾问：诺华；酬金（个体经营），咨询/顾问：Pharmamar；酬金（个体经营），咨询/顾问：Eisai；酬金（个体经营），咨询/顾问：礼来公司；酬金（个体经营），咨询/顾问：Celgene；酬金（个体经营），咨询/顾问：Astellas；酬金（个体经营），咨询/顾问：Amgen; 酬金（个体经营），咨询/顾问：辉瑞公司。M. Ramos Vazquez：Honoraria（个体经营），咨询/顾问：AstraZeneca；酬金（个体经营），咨询/顾问：Roche；Honoraria（个体经营），咨询/顾问：诺华；酬金（个体经营），咨询/顾问：辉瑞公司。J.Cortés：Honoraria（个体），Honoraria（机构），咨询/顾问：罗氏；酬金（个体经营），咨询/顾问：Celgene；咨询/顾问：Cellestia；酬金（机构），咨询/顾问：阿斯利康；咨询/顾问：Biothera Pharmaceutical；咨询/顾问：Merus；咨询/顾问：西雅图遗传学；咨询/顾问：第一三共；咨询/顾问：Erytech；咨询/顾问：Athenex；咨询/顾问：Polyphor；酬金（个体经营），咨询/顾问：礼来公司；酬金（机构），咨询/顾问：Servier；酬金（自己），酬金（机构），咨询/顾问：MSD; 咨询/顾问：GSK；Honoraria（个体）：诺华; 荣誉（个人），荣誉（机构）：卫材；荣誉（个人），荣誉（机构）：Pfizer；Honoraria（个体经营）：Samsung Bioepis；酬金（机构），MedSIR（股票，专利和知识产权）：Ariad Pharmaceuticals。Baxalta GMBH /军人事务。拜耳医疗保健。Guardanth Health。皮库尔疗法。Puma C.伦敦玛丽皇后大学。西根 所有其他作者都声明没有利益冲突。