A Global First-in-Human Study in NSCLC, HNSCC, and Solid Tumors With Azirkitug as a Single Agent and in Combination(s) With Budigalimab, Bevacizumab, or Telisotuzumab Adizutecan
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 694
- 试验地点
- 83
- 主要终点
- Time to Maximum Observed Serum Concentration (Tmax) of ABBV-514
研究概览
简要总结
Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. Non-Small Cell Lung Cancer (NSCLC) is a solid tumor, a disease in which cancer cells form in the tissues of the lung. Head and Neck Squamous Cell Carcinoma (HNSCC) is a solid tumor, a disease in which cancer cells form in the tissues of the head and neck. The purpose of this study is to assess adverse events and pharmacokinetics of azirkitug as a monotherapy and in combination with budigalimab, bevacizumab, or telisotuzumab adizutecan.
Bevacizumab is an approved product, while budigalimab, azirkitug, and telisotuzumab adizutecan are investigational drugs being developed for the treatment of NSCLC, HNSCC, and other solid tumors. Study doctors put the participants in groups called treatment arms. The maximum-tolerated dose (MTD)/maximum administered dose (MAD) of azirkitug will be explored. Each treatment arm receives a different dose of azirkitug in monotherapy and in combination with budigalimab, bevacizumab, or telisotuzumab adizutecan. Approximately 694 adult participants will be enrolled in the study across approximately 80 sites worldwide.
Participants will receive azirkitug as a monotherapy or in combination with budigalimab, bevacizumab, or telisotuzumab adizutecan as an Intravenous (IV) Infusion for an estimated treatment period of up to 2 years.
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 a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
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
- •Pre Treatment biopsy or archive tissue within 6 months without intervening treatment
- •Eastern Cooperative Oncology Group (ECOG) performance status of <= 0 or 1 and a life expectancy of >= 3 months.
- •Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST)
- •Laboratory values meeting criteria outlined in the protocol
- •NSCLC - Advanced or metastatic progressed on standard of care (SOC) including chemotherapy and prior anti-PD-(L)1 antibody (separately or in combination). Actionable gene alterations are eligible if failed targeted therapeutic options.
- •HSNCC - Advanced/metastatic progressed on platinum and PD-1/PD-LI in recurrent or metastatic setting.
- •Micro Satellite Stable Colorectal Cancer (MSS-CRC) - Progressed on Oxaliplatin, Irinotecan, a fluoropyrimidine, anti-EGFR, VEGF or VEGFR therapies, BRAFV600E or HER2, other targetable mutations targeted with locally approved therapy, TAS-102, Regorafenib and not MSI-h or MMR-deficient
- •Gastric and Gastroesophageal Junction adenocarcinoma (GEA) - Advanced/metastatic progressed on at least 1 prior cytotoxic chemotherapeutic regimen and if applicable immune checkpoint inhibitor and/or HER2 therapy
- •High-Grade Serous Ovarian Cancer (HGSOC) - Progressed serous epithelial ovarian, fallopian tube or primary peritoneal cancer post SOC and not eligible for surgical resection. Platinum resistant cannot have >5 lines of prior therapy.
- •Pancreatic Adenocarcinoma (PDAC) - Advanced/metastatic progressed after SOC. Includes adenosquamous carcinoma and post-Whipple.
- •Triple Negative Breast Cancer (TNBC) - Progressed after 1 or 2 systemic therapy that must have included taxane and treatment naïve to immunotherapy targeting T-cell co-stimulation
排除标准
- •Pancreatic Ductal Adenocarcinoma (PDAC) - Excludes neuroendocrine or acinar pancreatic carcinoma and participants with coagulopathy or at risk of or history of Deep vein thrombosis (DVT)/PE
- •No major surgery within 28 days prior to dosing
- •No active autoimmune/immunodeficiency disease with limited exceptions
- •Combination treatment excludes participants treated with anti-programmed cell death protein 1(PD-1)/Programmed cell death ligand 1 (PD-L1) who had immune mediated toxicity G3 or greater, interstitial lung disease, or hypersensitivity Combination treatment may also require no significant cardiac deficiencies and/or events
- •Pregnancy
- •Excluded medications include anticancer therapy within 5 half-live or 28 days (whichever is shorter), agent targeting Chemokine Receptor (CCR)8, live vaccines, immunosuppressive medication with limited exceptions
研究组 & 干预措施
Part 4 Dose Optimization & Randomization Azirkitug+Budigalimab
Participants will receive Azirkitug in combination with budigalimab.
干预措施: Azirkitug (Drug)
Part 1 Dose Escalation: Azirkitug
Participants will receive Azirkitug.
干预措施: Azirkitug (Drug)
Part 1 Dose Escalation: Azirkitug + Budigalimab
Participants will receive Azirkitug in combination with budigalimab.
干预措施: Azirkitug (Drug)
Part 7 Dose Expansion: Azirkitug + Budigalimab
Participants will receive Azirkitug at recommended dose determined in Dose Escalation portion in combination with budigalimab.
干预措施: Azirkitug (Drug)
Part 3 Dose Expansion: Azirkitug + Budigalimab
Participants will receive Azirkitug at recommended dose determined in Dose Escalation portion in combination with budigalimab.
干预措施: Azirkitug (Drug)
Part 8 Dose Expansion: Azirkitug + Bevacizumab
Participants will receive Azirkitug at recommended dose determined in Dose Escalation portion in combination with bevacizumab.
干预措施: Azirkitug (Drug)
Part 9 Dose Expansion: Azirkitug + Budigalimab
Participants will receive Azirkitug at recommended dose determined in Dose Escalation portion in combination with budigalimab.
干预措施: Azirkitug (Drug)
Part 10 Dose Expansion: Azirkitug+Telisotuzumab Adizutecan
Participants will receive Azirkitug at recommended dose determined in the safety lead in portion in combination with telisotuzumab adizutecan.
干预措施: Azirkitug (Drug)
Part 10 Safety Lead In: Azirkitug + Telisotuzumab Adizutecan
Participants will receive Azirkitug in combination with telisotuzumab adizutecan.
干预措施: Azirkitug (Drug)
Part 10 Dose Expansion: Azirkitug+Telisotuzumab Adizutecan
Participants will receive Azirkitug at recommended dose determined in the safety lead in portion in combination with telisotuzumab adizutecan.
干预措施: Telisotuzumab Adizutecan (Drug)
Part 3 Dose Expansion: Azirkitug + Budigalimab
Participants will receive Azirkitug at recommended dose determined in Dose Escalation portion in combination with budigalimab.
干预措施: Budigalimab (Drug)
Part 2 Dose Expansion: Azirkitug + Budigalimab
Participants will receive Azirkitug at recommended dose determined in Dose Escalation portion in combination with budigalimab.
干预措施: Budigalimab (Drug)
Part 6 Dose Expansion: Azirkitug + Budigalimab
Participants will receive Azirkitug at recommended dose determined in Dose Escalation portion in combination with budigalimab.
干预措施: Azirkitug (Drug)
Part 7 Dose Expansion: Azirkitug + Budigalimab
Participants will receive Azirkitug at recommended dose determined in Dose Escalation portion in combination with budigalimab.
干预措施: Budigalimab (Drug)
Part 5 Dose Expansion: Azirkitug + Budigalimab
Participants will receive Azirkitug at recommended dose determined in Dose Escalation portion in combination with budigalimab.
干预措施: Budigalimab (Drug)
Part 10 Safety Lead In: Azirkitug + Telisotuzumab Adizutecan
Participants will receive Azirkitug in combination with telisotuzumab adizutecan.
干预措施: Telisotuzumab Adizutecan (Drug)
Part 4 Dose Optimization & Randomization Azirkitug+Budigalimab
Participants will receive Azirkitug in combination with budigalimab.
干预措施: Budigalimab (Drug)
Part 2 Dose Expansion: Azirkitug + Budigalimab
Participants will receive Azirkitug at recommended dose determined in Dose Escalation portion in combination with budigalimab.
干预措施: Azirkitug (Drug)
Part 1 Dose Escalation: Azirkitug + Budigalimab
Participants will receive Azirkitug in combination with budigalimab.
干预措施: Budigalimab (Drug)
Part 8 Safety Lead In: Azirkitug + Bevacizumab
Participants will receive Azirkitug in combination with bevacizumab.
干预措施: Azirkitug (Drug)
Part 2 Dose Expansion: Azirkitug
Participants will receive Azirkitug at recommended dose determined in Dose Escalation portion.
干预措施: Azirkitug (Drug)
Part 4 Dose Expansion: Azirkitug
Participants will receive Azirkitug at recommended dose determined in Dose Escalation portion.
干预措施: Azirkitug (Drug)
Part 4 Dose Expansion: Azirkitug + Budigalimab
Participants will receive Azirkitug in combination with budigalimab.
干预措施: Azirkitug (Drug)
Part 4 Dose Expansion: Azirkitug + Budigalimab
Participants will receive Azirkitug in combination with budigalimab.
干预措施: Budigalimab (Drug)
Part 4 Dose Optimization and Randomization: Azirkitug
Participants will receive Azirkitug at recommended dose determined in Dose Escalation portion.
干预措施: Azirkitug (Drug)
Part 5 Dose Expansion: Azirkitug + Budigalimab
Participants will receive Azirkitug at recommended dose determined in Dose Escalation portion in combination with budigalimab.
干预措施: Azirkitug (Drug)
Part 9 Dose Expansion: Azirkitug + Budigalimab
Participants will receive Azirkitug at recommended dose determined in Dose Escalation portion in combination with budigalimab.
干预措施: Budigalimab (Drug)
Part 6 Dose Expansion: Azirkitug + Budigalimab
Participants will receive Azirkitug at recommended dose determined in Dose Escalation portion in combination with budigalimab.
干预措施: Budigalimab (Drug)
Part 8 Safety Lead In: Azirkitug + Bevacizumab
Participants will receive Azirkitug in combination with bevacizumab.
干预措施: Bevacizumab (Drug)
Part 8 Dose Expansion: Azirkitug + Bevacizumab
Participants will receive Azirkitug at recommended dose determined in Dose Escalation portion in combination with bevacizumab.
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Time to Maximum Observed Serum Concentration (Tmax) of ABBV-514
时间窗: Up to 2 Years
Time to maximum Observed Serum Concentration (Tmax) of of ABBV-514.
Antidrug Antibody (ADA)
时间窗: Up to 2 Years
Incidence and concentration of anti-drug antibodies.
Number of Participants with Adverse Events (AE)
时间窗: Up to 2 Years
An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Terminal Elimination Half-Life (t1/2) of ABBV-514
时间窗: Up to 2 Years
Terminal elimination half-life (t1/2) of ABBV-514.
Neutralizing Antidrug Antibody (nADA)
时间窗: Up to 2 Years
Incidence and concentration of neutralizing anti-drug antibodies.
Maximum Observed Serum Concentration (Cmax) of ABBV-514
时间窗: Up to 2 Years
Maximum Observed Serum Concentration (Cmax) of of ABBV-514.
Area Under the Serum Concentration Versus Time Curve (AUC) of ABBV-514
时间窗: Up to 2 Years
Area under the serum concentration versus time curve (AUC) of ABBV-514.
Maximum Observed Serum Concentration (Cmax) of Azirkitug
时间窗: Up to 2 Years
Maximum Observed Serum Concentration (Cmax) of azirkitug.
Time to Maximum Observed Serum Concentration (Tmax) of Azirkitug
时间窗: Up to 2 Years
Time to maximum Observed Serum Concentration (Tmax) of azirkitug.
Terminal Elimination Half-Life (t1/2) of Azirkitug
时间窗: Up to 2 Years
Terminal elimination half-life (t1/2) of azirkitug.
Area Under the Serum Concentration Versus Time Curve (AUC) of Azirkitug
时间窗: Up to 2 Years
Area under the serum concentration versus time curve (AUC) of azirkitug.
Azirkitug Antidrug Antibody (ADA)
时间窗: Up to 2 Years
Incidence and concentration of azirkitug anti-drug antibodies.
Azirkitug Neutralizing Antidrug Antibody (nADA)
时间窗: Up to 2 Years
Incidence and concentration of azirkitug neutralizing anti-drug antibodies.
Cmax of Budigalimab
时间窗: Up to 2 Years
Cmax of budigalimab.
Tmax of Budigalimab
时间窗: Up to 2 Years
Tmax of budigalimab.
t1/2 of Budigalimab
时间窗: Up to 2 Years
t1/2 of budigalimab.
AUC of Budigalimab
时间窗: Up to 2 Years
AUC of budigalimab.
Budigalimab ADA
时间窗: Up to 2 Years
Incidence and concentration of budigalimab ADA.
Budigalimab nADA
时间窗: Up to 2 Years
Incidence and concentration of budigalimab nADA.
Cmax of Telisotuzumab Adizutecan
时间窗: Up to 2 Years
Cmax of telisotuzumab adizutecan.
Tmax of Telisotuzumab Adizutecan
时间窗: Up to 2 Years
Tmax of telisotuzumab adizutecan.
t1/2 of Telisotuzumab Adizutecan
时间窗: Up to 2 Years
t1/2 of telisotuzumab adizutecan.
AUC of Telisotuzumab Adizutecan
时间窗: Up to 2 Years
AUC of telisotuzumab adizutecan.
Telisotuzumab Adizutecan ADA
时间窗: Up to 2 Years
Incidence and concentration of telisotuzumab adizutecan ADA.
Telisotuzumab Adizutecan nADA
时间窗: Up to 2 Years
Incidence and concentration of telisotuzumab adizutecan nADA.
次要结局
未报告次要终点