PO.CTP01.03 · 进行中的临床试验

Palbociclib（P）治疗CCND1扩增（amp）肺癌（LC）患者（pts）：靶向药物与分析利用注册研究（TAPUR）的结果

Palbociclib (P) in patients (pts) with lung cancer (LC) with CCND1 amplification (amp): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study

编号 CT211 展板 6 时间 4/21 09:00–12:00 区域 Section 51 主讲 Evan Pisick, MD

分会场 Phase II and Phase III Clinical Trials in Progress

该海报暂无可下载的资料 AACR 官方页面

作者与单位 Authors & Affiliations

Evan Pisick¹, Michael Rothe², Elizabeth Garrett-Mayer², Christopher M. Reynolds³, Bamidele Adesunloye⁴, Ramya Thota⁵, Kathryn F. Mileham⁶, Kelly Lynch⁷, Rachel E. Sanborn⁸, Timothy L. Cannon⁹, Justin T. Moyers¹⁰, Janet Tu¹¹, Mehmet Akce¹², Abigail Gregory², Dominique C. Hinshaw², Gina N. Grantham², Susan Halabi¹³, Richard L. Schilsky²

¹City of Hope - Chicago, Zion, IL,²American Society of Clinical Oncology, Alexandria, VA,³Michigan Cancer Research Consortium, Ypsilanti, MI,⁴City of Hope - Atlanta, Atlanta, GA,⁵Intermountain Healthcare, Murray, UT,⁶Atrium Health Levine Cancer Institute, Wake Forest University School of Medicine, Charlotte, NC,⁷Cancer Research Consortium of West Michigan, Norton Shores, MI,⁸Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR,⁹Inova Schar Cancer Institute, Fairfax, VA,¹⁰The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate, Los Angeles, CA,¹¹Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX,¹²O’Neal Comprehensive Cancer Center, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL,¹³Duke University Medical Center, Durham, NC

摘要 Abstract

中文摘要

背景：TAPUR是一项II期篮子研究，评估市售靶向药物在携带特定基因组改变的晚期癌症患者中的抗肿瘤活性。本文报告一个采用P治疗的CCND1 amp LC患者队列的结果。方法：符合条件的患者患有非小细胞（NSCLC）或小细胞（SCLC）LC、有可测量病灶、ECOG体能状态（PS）0-2、器官功能充足，且无剩余标准治疗（tx）选择。基因组检测在经CLIA认证、CAP认可的场所选定实验室进行。扩增临界值按NGS供应商定义。肿瘤不得携带RB基因突变（mut）。P给药方案为每次一粒125 mg胶囊口服，每日一次，服用21天后停药7天，直至疾病进展。主要终点为研究者评估的疾病控制（DC），定义为按RECIST v1.1标准的客观缓解（OR）或持续至少16+周（wks）的疾病稳定（SD16+）。采用Simon两阶段设计检验无效DC率15%对35%（把握度=0.85；alpha=0.10）。次要终点为无进展生存期（PFS）、总生存期（OS）、OR、SD持续时间和安全性。结果：共入组29例携带CCND1 amp（n=28）或CCND1 amp及mut（n=1）的NSCLC（n=28）或SCLC（n=1）患者。KRAS和CDKN2A/B的共存改变包括：KRAS mut（n=2）、amp（n=2）以及mut及amp（n=1）；CDKN2A mut（n=6）、缺失（del；n=1）以及mut及del（n=1）。1例NSCLC患者无法评估疗效。表格显示人口统计学特征、结局和毒性。5例患者观察到SD16+，均为携带CCND1 amp的NSCLC，DC率为25%（单侧90% CI，10至100），OR率为0%（95% CI，0至12）。无效DC率未被拒绝（p=0.28）。4例患者发生≥1次3-4级tx相关不良事件（AE）或严重不良事件（SAE）。结论：P未达到预设标准以宣布在CCND1 amp LC患者中存在活性信号。应为这些患者考虑其他治疗，包括临床试验中提供的治疗。表格：人口统计学特征、毒性（N=29）和疗效结局（n=28）中位（Med）年龄，岁（范围）63（34，84）女性，例数（%）11（38） ECOG PS，例数（%）0 4（14） 1 20（69） 2 5（17）既往全身治疗方案，例数（%）1 1（3） 2 8（28） ≥3 20（69） DC率，%（OR或SD16+）（单侧90% CI），p值 25（10，100），p = 0.28 OR率，%（95% CI）0（0，12）中位PFS，周（95% CI）9（7，16）中位OS，周（95% CI）25（17，41） SD16+患者的中位SD持续时间（范围），周 25（16-30） tx相关AE或SAE（3-4级）患者数 1 AE 2 4（14） SAE 3 1（3） 1 患者可能经历了一次或多次事件 2 白细胞减少、淋巴细胞减少、中性粒细胞减少、疼痛 3 脓毒症

查看英文原文 English abstract

Background: TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with specific genomic alterations. Results in a cohort of pts with LC with CCND1 amp treated with P are reported. Methods: Eligible pts had non-small cell (NSCLC) or small cell (SCLC) LC, measurable disease, ECOG performance status (PS) 0-2, adequate organ function, and no remaining standard treatment (tx) options. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Amp cut-offs were defined per NGS providers. Tumors must not have had mutations (mut) in the RB gene. P dosing was one 125 mg capsule taken orally once daily for 21 days followed by 7 days off, until disease progression. Primary endpoint was disease control (DC) per investigator defined as objective response (OR) or stable disease (SD) of at least 16+ weeks (wks) duration (SD16+) per RECIST v1.1. Simon 2-stage design tested the null DC rate of 15% vs. 35% (power = 0.85; alpha = 0.10). Secondary endpoints were progression-free survival (PFS), overall survival (OS), OR, duration of SD, and safety. Results: 29 pts with NSCLC (n=28) or SCLC (n=1) with CCND1 amp (n=28) or CCND1 amp and mut (n=1) were enrolled. Co-alterations in KRAS and CDKN2A/B included: KRAS mut (n=2), amp (n=2), and mut and amp (n=1); CDKN2A mut (n=6), deletion (del; n=1), and mut and del (n=1). 1 pt with NSCLC was unevaluable for efficacy. Table shows demographics, outcomes, and toxicity. SD16+ was observed in 5 pts, all with NSCLC and CCND1 amp for a DC rate of 25% (1-sided 90% CI, 10 to 100) and an OR rate of 0% (95% CI, 0 to 12). The null DC rate was not rejected (p=0.28). 4 pts had ≥1 grade 3-4 tx-related adverse events (AE) or serious adverse events (SAE). Conclusions: P did not meet prespecified criteria to declare a signal of activity in pts with LC with CCND1 amp. Other tx should be considered for these pts, including tx offered in clinical trials. Table: Demographics, Toxicity (N=29), and Efficacy Outcomes (n=28) Median (Med) age, years (range) 63 (34, 84) Female, No. (%) 11 (38) ECOG PS, No. (%) 0 4 (14) 1 20 (69) 2 5 (17) Prior systemic regimens, No. (%) 1 1 (3) 2 8 (28) ≥3 20 (69) DC rate, % (OR or SD16+) (1-sided 90% CI), p-value 25 (10, 100), p = 0.28 OR rate, % (95% CI) 0 (0, 12) Med PFS, wks (95% CI) 9 (7, 16) Med OS, wks (95% CI) 25 (17, 41) Med duration SD in pts with SD16+ (range), wks 25 (16-30) Number of pts 1 with tx-related AE or SAE (grade 3-4) AE 2 4 (14) SAE 3 1 (3) 1 Patients may have experienced one or more events 2 Leukopenia, lymphopenia, neutropenia, pain 3 Sepsis

利益披露 Disclosure

E. Pisick, None.. M. Rothe, None.. E. Garrett-Mayer, None.. C. M. Reynolds, None. B. Adesunloye, Eisai Other, Advisory Board. Pfizer Other, Advisory Board. Exellixis Other, Advisory Board. R. Thota, None. K. F. Mileham, Abbvie Independent Contractor, Other, Advisory board. Astra Zeneca Independent Contractor, Other, Advisory board. Bayer Independent Contractor, Other, Advisory Board. Genentech Independent Contractor, Other, Advisory Board. Janssen Independent Contractor, Other, Advisory Board. Merck Independent Contractor, Other, Advisory Board. Nuvation Bio Independent Contractor, Other, Advisory Board. Takeda Independent Contractor, Other, Advisory Board. Tempus ). K. Lynch, None. R. E. Sanborn, AstraZeneca, Bristol Myers Squibb, Merck ). Abbive, Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, Curio Science, Daiichi Sankyo, G1 Therapeutics, GE Healthcare, Gilead Sciences, IDEOlogy Health, Illumina, InhibRx, Janssen Oncology Independent Contractor. Johnson & Johnson/Janssen, Lilly Oncology, Natera, OncLive/MJH Life Sciences, OSE Immunotherapies, Pfizer, Rigel, Sanofi/Aventis, Targeted Oncology Independent Contractor. Amgen, AstraZeneca, G1 Therapeutics, GE Healthcare, Gilead Sciences, GlaxoSmithKline, Janssen Oncology, Sanofi/Aventis Other, Advisory Board. OSE Immunotherapies Other, Data Safety Monitoring Board. AstraZeneca, Merck Other, Investigator Sponsored Trial. T. L. Cannon, Astra Zeneca Independent Contractor, Other, consultant one time. Revolution Medicine Independent Contractor, Other, consultant one time. J. T. Moyers, None.. J. Tu, None. M. Akce, Partner Therapeutics Other, Consulting or advisory role. BMS Other, Consulting or advisory role and Research support to institution. Daichii Sankyo Other, Consulting or advisory role. Taiho Other, Consulting or advisory role. Incyte Other, Consulting or advisory role. Genentech Other, Consulting or advisory role and Research support to institution. AstraZeneca Other, Consulting or advisory role and Research support to institution. Curio Science Other, Consulting or advisory role. GSK Other, Consulting or advisory role. ProDa BioTech Other, Research support to institution. A. Gregory, Pfizer Other, Employment of Immediate Family Member Stock options held by Immediate Family Member. D. C. Hinshaw, None.. G. N. Grantham, None. S. Halabi, BMS Other, Member of DSMB. CG Oncology Other, Member of DSMB. Janssen Other, Member of DSMB. Sanofi Other, Member of DSMB. R. L. Schilsky, Clarified Precision Medicine Stock Option, Other, Leadership Position. Leap Therapeutics Stock, Other, Leadership Position. Cellworks Independent Contractor, Stock Option, Other, Consulting/Advisory Role. ZephyrAI Independent Contractor, Other, Consulting/Advisory Role. Flatiron Health Independent Contractor, Other, Consulting or Advisory Role. Toray Industries Other, Honoraria for service on a study for DSMB. AstraZeneca Other, Research Funding to ASCO in support of the TAPUR Study. Bayer Other, Research Funding to ASCO in support of the TAPUR Study. Bristol Myers Squibb Other, Research Funding to ASCO in support of the TAPUR Study. Genentech/Roche Other, Research Funding to ASCO in support of the TAPUR Study. Lilly Other, Research Funding to ASCO in support of the TAPUR Study. Merck Other, Research Funding to ASCO in support of the TAPUR Study. Pfizer Other, Research Funding to ASCO in support of the TAPUR Study. Boehringer Ingelheim Other, Research Funding to ASCO in support of the TAPUR Study. Taiho Oncology Other, Research Funding to ASCO in support of the TAPUR Study. WUGEN, Inc. Other, Honoraria for service as a DSMB Member. AbbVie Other, Honorarium for lecture. Sygnomics Independent Contractor, Other, consulting or advisory role.

← 返回 AACR 2026 检索