Study to Assess Adverse Events and Change in Disease Activity in Adult Participants With Advanced Solid Tumors Receiving Intravenous (IV) ABBV-400 as Monotherapy and in Combination With IV Bevacizumab
关于
癌症是身体特定部位的细胞不受控制地生长和繁殖的一种情况. The purpose of this study is to assess adverse events and change in disease activity when ABBV-400 is given to adult participants to treat advanced solid tumors.
ABBV-400是一种用于治疗晚期实体瘤的研究药物. 研究医生将参与者分成治疗组. 将探讨推荐的2期剂量(RP2D). 每个治疗组接受不同剂量的ABBV-400. 该研究将包括一个剂量递增阶段，以确定ABBV-400的最佳剂量, 随后是剂量扩展阶段，以确认剂量和与贝伐单抗的联合. 大约500名患有NSCLC的成年参与者, gastroesophageal adenocarcinoma/胃食管结腺癌(GEA) and 结直肠癌(CRC) or advanced solid tumors, will be enrolled in the study in approximately 7-10 sites in the Dose Escalation phase and 85-95 sites in the Dose Expansion phase worldwide.
剂量递增武器, 参与者将接受静脉(IV)递增剂量的ABBV-400单药治疗. 剂量膨胀臂, participants in the following advanced solid tumor indications: non-squamous NSCLC with wildtype EGFR-expression (wtEGFR NSCLC) [Part 2i] or mutated EGFR-expression (mutEGFR NSCLC) [Part 2ii], 鳞状非小细胞肺癌[第2iii部分], GEA [Part 3]将接受静脉(IV) ABBV-400单药治疗, CRC参与者将扩大接受IV ABBV-400单药治疗[Part 4], MET扩增的参与者将在扩展期接受IV ABBV-400单药治疗[第5部分], MET突变参与者将扩大接受IV ABBV-400单药治疗[Part 6], participants CRC safety lead in will receive escalating doses of IV ABBV-400 in combination with IV bevacizumab [Part 7a], and participants CRC dose optimization in will the low or high dose of IV ABBV-400 determined in Part 7a in combination with IV bevacizumab or oral trifluridine/tipiracil (TAS-102) tablets [Part 7b].
与他们的护理标准相比，本试验参与者的治疗负担可能更高. Participants will attend regular visits during the study at an approved institution (hospital or clinic). 医疗评估将经常检查治疗效果, 血液测试, 问卷调查和副作用.
资格
入选标准:
- 恶性实体瘤的诊断(世界卫生组织[WHO]标准).
- 根据实体肿瘤反应评价标准(RECIST) v1可测量的疾病.1.
- For Part 1 only - advanced solid tumors including (but not limited to) non-small cell lung cancer (NSCLC), 头颈部鳞状细胞癌, 胃食管结腺癌(GEA), 结直肠癌(CRC), 和肾细胞癌(RCC), who have progressed on all standard of care therapy and are not amenable to surgical resection or other approved therapeutic options that have demonstrated clinical benefit.
- For Part 2 only - advanced non-squamous squamous Non-Small Cell 肺癌 (NSCLC) that have progressed after treatment with at least:
- Platinum-based chemotherapy and an immune checkpoint inhibitor and/or appropriate targeted therapy for an actionable gene alteration, 如果适用的话, 非鳞状wtEGFR NSCLC (Part 2i)和鳞状NSCLC (Part 2iii).
- Platinum-based chemotherapy doublet and tyrosine kinase inhibitor(s) (TKI[s]) for non- squamous mutEGFR NSCLC (Part 2ii).
- Must have no more than 2 lines of prior cytotoxic chemotherapy excluding adjuvant therapy and must have advanced NSCLC that is not amenable to surgical resection or other approved therapeutic options that have demonstrated clinical benefit.
- For Part 3 only - Participants with advanced GEA that has progressed after treatment with at least 1 prior cytotoxic chemotherapeutic regimen for locally advanced or metastatic disease and have not received more than 2 prior lines of cytotoxic chemotherapy regimens. 参与者必须有进步
- 如果适用，使用免疫检查点抑制剂.
- 如果适用，适当的可用疗法，包括her2导向疗法. Participants who are considered ineligible for or are intolerant of standard therapy per investigator are eligible.
- For Part 4 only - Participants with history of advanced histopathologically or cytologically confirmed 结直肠癌(CRC) that does not harbor the BRAF V600E mutation and are not dMMR+/MSI-Hi with progression on:
- 氟嘧啶(e.g.、5-氟尿嘧啶或卡培他滨).
- 铂.
- 伊立替康.
- 如适用，抗egfr(包括但不限于西妥昔单抗或帕尼单抗).
- 如果适用的话, anti-vascular endothelial growth factor (VEGF) monoclonal antibody (including but not limited to bevacizumab, ramucirumab, 或aflibercept).
- 如果适用，进行靶向治疗
- Participants who are considered ineligible for or are intolerant of standard therapy per investigator are eligible. 既往接受过trifluridine/tipiracil (TAS-102)或Regorafenib治疗的受试者符合条件.
- For Part 5 only - participants with advanced histologically or cytologically confirmed solid tumors characterized by MET amplification who are not amenable to surgical resection and who have disease progression after at least one prior systemic therapy and/or who have no satisfactory alternative treatment options. 对标准治疗不耐受的参与者符合条件. For Part 6 only - Participants with advanced histologically or cytologically confirmed solid tumors harboring MET mutations including: mutations in the tyrosine kinase domain, the juxtamembrane region and the extracellular domain (as locally determined by next-generation sequencing (NGS) or a validated qPCR on tissue), who are not amenable to surgical resection and who have disease progression after at least one prior systemic therapy and/or who have no satisfactory alternative treatment options.
- 对标准治疗不耐受者为合格
- For Part 7 (CRC combination) only: Participants with history of advanced histopathologically or cytologically confirmed CRC that does not harbor the mutation and are not dMMR+/MSI-H with progression on:
- 氟嘧啶(e.g.、5-氟尿嘧啶或卡培他滨)
- 铂
- 伊立替康
- 如适用，抗egfr(包括但不限于西妥昔单抗或帕尼单抗)
- 如果适用的话, anti-vascular endothelial growth factor (VEGF) monoclonal antibody (including but not limited to bevacizumab, ramucirumab, 或aflibercept)
- 如果适用，进行靶向治疗 Participants who are considered ineligible for or are intolerant of standard therapy per investigator are eligible. 先前接受TAS-102或regorafenib治疗的参与者不符合条件.
- 东部肿瘤合作组(ECOG)绩效状态(PS)为0或1.
- 实验室值符合方案中列出的标准.
排除标准:
- History of interstitial lung disease (ILD) or pneumonitis that required treatment with systemic steroids, 也没有活动性ILD或胸部CT扫描的证据..
- 特发性肺纤维化病史，组织性肺炎(如.g.如闭塞性细支气管炎)、药物性肺炎或特发性肺炎.
- 如方案中所述，有临床意义的、并发的肺部特异性疾病史.
- 仅对于第7部分:先前的TAS-102或瑞非尼治疗的参与者不符合条件.
加入这个试验
- 皇冠hga025大学圣莫尼卡分校
- 皇冠hga025大学洛杉矶分校韦斯特伍德