【佳學基因靶向藥物基因檢測】IMAGENE 試驗：多中心、概念驗證、II 期研究，評估尼拉帕尼與 PD-1 抑制劑聯(lián)合治療具有同源重組修復基因突變的實體癌患者的療效和安全性

組織腫瘤檢測一次——目標

小組討論研究基因組織學知識要點《重要分析位點的影響及性質(zhì)》《BMC Cancer》在?2022 Dec 9;22(1):1292.發(fā)表了一篇題目為《Clinical Trial》腫瘤靶向藥物治療基因檢測臨床研究文章。該研究由Taigo Kato,?Nobuaki Matsubara,?Masaki Shiota,?Masatoshi Eto,?Takahiro Osawa,?Takashige Abe,?Nobuo Shinohara,?Yota Yasumizu,?Nobuyuki Tanaka,?Mototsugu Oya,?Koshiro Nishimoto,?Takuji Hayashi,?Masashi Nakayama,?Takahiro Kojima,?Kenjiro Namikawa,?Takao Fujisawa,?Susumu Okano,?Eisuke Hida,?Yoshiaki Nakamura,?Hideaki Bando,?Takayuki Yoshino,?Norio Nonomura等完成。促進了腫瘤的正確治療與個性化用藥的發(fā)展，進一步強調(diào)了基因信息檢測與分析的重要性。

腫瘤基因檢測及靶向藥物治療研究關鍵詞：

同源重組修復,免疫檢查點抑制劑,尼拉帕尼, PARP抑制劑,腫瘤不可知療法。

腫瘤治療檢測基因臨床應用結(jié)果

靶向藥物研究立項的依據(jù)：先前的臨床試驗已經(jīng)證明了聚（ADP-核糖）聚合酶（PARP）抑制劑（PARPis）對涉及同源重組修復（HRR）基因突變的癌癥患者的潛在療效。此外，隨著腫瘤突變負擔的增加，HRR 基因突變的癌癥可以通過免疫檢查點抑制劑 (ICI) 得到有效治療。我們提議開展一項多中心、單組 II 期試驗（IMAGENE 試驗），以評估尼拉帕尼 (PARPi) 與程序性細胞死亡 1 抑制劑聯(lián)合治療對 HRR 基因突變癌癥患者的療效和安全性，這些患者難治性使用基于下一代測序的循環(huán)腫瘤 DNA (ctDNA) 和腫瘤組織分析的 ICIs 療法。先前 ICI 治療后進展；和 Eastern Cooperative Oncology Group Performance Status ≤ 1。主要終點是所有患者的確認客觀反應率 (ORR)。次要終點包括使用 Caris Assure（CARIS，美國）確認的 ctDNA 的 HRR 基因突變患者的 ORR。 IMAGENE 試驗的目標樣本量為 57 名患者。將使用 Caris Assure、蛋白質(zhì)組分析和 T 細胞庫分析同時進行生物標志物分析，以揭示外周血中的腫瘤免疫監(jiān)視。預期靶向藥物研究的客觀數(shù)據(jù)：我們的試驗旨在證實 PARPi 加 ICI 聯(lián)合治療對 ICI 耐藥患者的臨床益處.此外，通過轉(zhuǎn)化研究，我們的試驗將闡明哪些患者即使在 ICIs 失敗后仍可從 HRR 基因突變腫瘤患者的靶向聯(lián)合治療中獲益。試驗注冊：IMAGENE 試驗：jRCT，臨床試驗編號： jRCT2051210120，注冊日期：2021年11月9日。關鍵詞：同源重組修復；免疫檢查點抑制劑；尼拉帕尼； PARP抑制劑；腫瘤不可知療法。

腫瘤發(fā)生與革命國際數(shù)據(jù)庫描述：

Background:?Previous clinical trials have demonstrated the potential efficacy of poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) in patients with cancer involving homologous recombination repair (HRR) gene-mutation. Moreover, HRR gene-mutated cancers are effectively treated with immune checkpoint inhibitors (ICIs) with the increase in tumor mutation burden. We have proposed to conduct a multicenter, single-arm phase II trial (IMAGENE trial) for evaluating the efficacy and safety of niraparib (PARPi) plus programmed cell death-1 inhibitor combination therapy in patients with HRR gene-mutated cancers who are refractory to ICIs therapy using a next generation sequencing-based circulating tumor DNA (ctDNA) and tumor tissue analysis.Methods:?Key eligibility criteria for this trial includes HRR gene-mutated tumor determined by any cancer gene tests; progression after previous ICI treatment; and Eastern Cooperative Oncology Group Performance Status ≤ 1. The primary endpoint is the confirmed objective response rate (ORR) in all patients. The secondary endpoints include the confirmed ORR in patients with HRR gene-mutation of ctDNA using the Caris Assure (CARIS, USA). The target sample size of the IMAGENE trial is 57 patients. Biomarker analyses will be performed in parallel using the Caris Assure, proteome analysis, and T cell repertoire analysis to reveal tumor immunosurveillance in peripheral blood.Expected outcome:?Our trial aims to confirm the clinical benefit of PARPi plus ICI combination therapy in ICI-resistant patients. Furthermore, through translational research, our trial will shed light on which patients would benefit from the targeted combination therapy for patients with HRR gene-mutated tumor even after the failure of ICIs.Trial registration:?The IMAGENE trial: jRCT, Clinical trial no.: jRCT2051210120, Registered date: November 9, 2021.Keywords:?Homologous recombination repair; Immune checkpoint inhibitor; Niraparib; PARP inhibitor; Tumor-agnostic therapy.