A Phase 1 First in Human Study Evaluating Safety, Pharmacokinetics and Efficacy of ABBV-400 as Monotherapy and in Combination With Bevacizumab in Adult Subjects With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 520
- 试验地点
- 82
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. 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 is an investigational drug being developed for the treatment of advanced solid tumors. Study doctors put the participants in groups called treatment arms. The Recommended Phase 2 dose (RP2D) will be explored. Each treatment arm receives a different dose of ABBV-400. This study will include a dose escalation phase to determine the best dose of ABBV-400, followed by a dose expansion phase to confirm the dose and combination with bevacizumab. Approximately 500 adult participants with NSCLC, gastroesophageal adenocarcinoma/gastroesophagel junction adenocarcinoma (GEA) and colorectal cancer (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.
Dose escalation arms, participants will receive intravenous (IV) escalating doses of ABBV-400 monotherapy. Dose expansion arms, 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], squamous NSCLC [Part 2iii], GEA [Part 3] will receive intravenous (IV) ABBV-400 monotherapy, participants CRC will receive IV ABBV-400 monotherapy in expansion [Part 4], participants MET amplification will receive IV ABBV-400 monotherapy in expansion [Part 5], participants MET mutation will receive IV ABBV-400 monotherapy in expansion [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].
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of malignant solid tumor (World Health Organization [WHO] criteria).
- •Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.
- •For Part 1 only - advanced solid tumors including (but not limited to) non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), gastroesophagel junction adenocarcinoma (GEA), colorectal cancer (CRC), and renal cell carcinoma (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 Lung Cancer (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, if applicable, for non-squamous wtEGFR NSCLC (Part 2i) and squamous 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. Participants must have progressed on
- •If applicable, an immune checkpoint inhibitor.
- •If applicable, appropriate available therapies, including HER2-directed therapies.
- •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 colorectal cancer (CRC) that does not harbor the BRAF V600E mutation and are not dMMR+/MSI-Hi with progression on:
- •A fluoropyrimidine (e.g., 5-fluorouracil or capecitabine).
- •Oxaliplatin.
- •Irinotecan.
- •If applicable, anti-EGFR (including, but not limited to cetuximab or panitumumab).
- •If applicable, anti-vascular endothelial growth factor (VEGF) monoclonal antibody (including but not limited to bevacizumab, ramucirumab, or aflibercept).
- •If applicable, targeted therapy
- •Participants who are considered ineligible for or are intolerant of standard therapy per investigator are eligible. Prior trifluridine/tipiracil (TAS-102) or Regorafenib treated participants are eligible.
- •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. Participants who are intolerant to standard treatment are eligible.
- •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.
- •Intolerant to the standard treatment are eligible
- •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:
- •A fluoropyrimidine (e.g., 5-fluorouracil or capecitabine)
- •Oxaliplatin
- •Irinotecan
- •If applicable, anti-EGFR (including, but not limited to cetuximab or panitumumab)
- •If applicable, anti-vascular endothelial growth factor (VEGF) monoclonal antibody (including but not limited to bevacizumab, ramucirumab, or aflibercept)
- •If applicable, targeted therapy Participants who are considered ineligible for or are intolerant of standard therapy per investigator are eligible. Participants treated previously with TAS-102 or regorafenib are not eligible.
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or
- •Laboratory values meeting the criteria outlined in the protocol.
排除标准
- •History of interstitial lung disease (ILD) or pneumonitis that required treatment with systemic steroids, nor any evidence of active ILD or on screening chest CT scan..
- •History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis.
- •History of clinically significant, intercurrent lung-specific illnesses, as noted in the protocol.
- •For Part 7 only: Prior TAS-102 or regorafenib treated participants are not eligible.
研究组 & 干预措施
Part 1 (Monotherapy Dose Escalation)
Participants with advanced solid tumors will receive escalating doses of ABBV-400.
干预措施: ABBV-400 (Drug)
Part 2i (wtEGFR Non-Small Cell Lung Cancer [NSCLC])
Participants with non-squamous wtEGFR NSCLC will receive ABBV-400 at the Recommended Phase 2 dose (RP2D).
干预措施: ABBV-400 (Drug)
Part 2ii (mutEGFR NSCLC)
Participants with non-Squamous mutEGFR NSCLC will receive ABBV-400 at RP2D.
干预措施: ABBV-400 (Drug)
Part 2iii (Squamous NSCLC)
Participants with squamous NSCLC will receive ABBV-400 at RP2D.
干预措施: ABBV-400 (Drug)
Part 3 (Gastroesophageal Adenocarcinoma/Gastroesophagel Junct
Participants with gastroesophageal adenocarcinoma will receive ABBV-400 at the RP2D.
干预措施: ABBV-400 (Drug)
Part 4 (Colorectal Cancer)
Participants with Colorectal Cancer (CRC) will receive ABBV-400 at the RP2D and various dose levels for dose optimization.
干预措施: ABBV-400 (Drug)
Part 5 (MET Amplification)
Participants with mesenchymal-epithelial transition proto-oncogene (MET) amplification will receive ABBV-400 at the RP2D and various dose levels for dose optimization.
干预措施: ABBV-400 (Drug)
Part 6 (MET Mutation)
Participants with MET mutation will receive ABBV-400 at the RP2D and various dose levels for dose optimization.
干预措施: ABBV-400 (Drug)
Part 7a (Combination Dose Escalation)
Participants with CRC will receive escalating doses of ABBV-400 in combination with bevacizumab.
干预措施: ABBV-400 (Drug)
Part 7a (Combination Dose Escalation)
Participants with CRC will receive escalating doses of ABBV-400 in combination with bevacizumab.
干预措施: Bevacizumab (Drug)
Part 7bi (Combination Dose Optimization Low Dose)
Participants with CRC will receive the low dose determined in the dose escalation arm (Part 7a) of ABBV-400 in combination with bevacizumab.
干预措施: ABBV-400 (Drug)
Part 7bi (Combination Dose Optimization Low Dose)
Participants with CRC will receive the low dose determined in the dose escalation arm (Part 7a) of ABBV-400 in combination with bevacizumab.
干预措施: Bevacizumab (Drug)
Part 7bii (Combination Dose Optimization High Dose)
Participants with CRC will receive the high dose determined in the dose escalation arm (Part 7a) of ABBV-400 in combination with bevacizumab.
干预措施: ABBV-400 (Drug)
Part 7bii (Combination Dose Optimization High Dose)
Participants with CRC will receive the high dose determined in the dose escalation arm (Part 7a) of ABBV-400 in combination with bevacizumab.
干预措施: Bevacizumab (Drug)
Part 7biii (Combination Comparator)
Participants with CRC will receive trifluridine/tipiracil (TAS-102) in combination with bevacizumab.
干预措施: Trifluridine/Tipiracil (Drug)
Part 7biii (Combination Comparator)
Participants with CRC will receive trifluridine/tipiracil (TAS-102) in combination with bevacizumab.
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Up to 48 Months
ORR defined as percentage of participants with confirmed best overall response of Confirmed complete response (CR) and partial response (PR) per investigator review according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
次要结局
- Duration of Response (DOR) for Participants with Confirmed CR/PR per RECIST v1.1(Up to 48 Months)
- PFS per RECIST v1.1(Up to 48 Months)
- Overall survival (OS)(Up to 48 Months)
- Parts 1-6: ORR per Independent Central Review (ICR) in Participants with MET Amplification(Up to 48 Months)