A Phase 1/2 Multicenter, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of AO-176
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 57
- 试验地点
- 10
- 主要终点
- Safety of AO-176 assessed by adverse events and laboratory abnormalities
研究概览
简要总结
This is a first-in-human, Phase 1/2 multi-center, open-label, dose escalation and expansion study of AO-176 which will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and clinical effects of AO-176 in patients with advanced solid tumors.
详细描述
This is a first-in-human, Phase 1/2 multicenter, open-label, dose escalation and expansion study of AO-176 in patients with solid tumors. Part A of this study will examine escalating repeat doses of AO-176 monotherapy in patients with select advanced solid tumors, including epithelial ovarian carcinoma (EOC), which will include primary peritoneal and fallopian tube carcinoma; squamous cell carcinoma of the head and neck; endometrial carcinoma; castration resistant prostate cancer; non-small cell lung adenocarcinoma; papillary thyroid carcinoma; pleural or peritoneal malignant mesothelioma; and gastroesophageal adenocarcinoma, for which standard therapy proven to provide clinical benefit does not exist or is no longer effective.
Part B and Part C of this study will examine escalating repeat doses of AO-176 in combination with paclitaxel (Part B) or pembrolizumab (Part C) in platinum-resistant EOC, including primary peritoneal and fallopian tube carcinoma; endometrial carcinoma; and gastric adenocarcinoma/gastroesophageal adenocarcinoma.
The monotherapy and combination dose escalation portions of the study utilize a classic 3+3 design, with enrollment of 3 patients per cohort and expansion of the cohort in the event of a dose-limiting toxicity (DLT).
Once the maximum-tolerated dose (MTD)/recommended phase 2 dose (RP2D) has been established in dose escalation, tumor-specific dose expansion cohorts will be recruited to further assess safety and evaluate preliminary efficacy of AO-176 as monotherapy, in combination with paclitaxel, and in combination with pembrolizumab.
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
- 未提供
排除标准
- •Previous hypersensitivity reaction to treatment with another monoclonal antibody
- •Unresolved hypersensitivity to paclitaxel or any of its excipients (Part B only). Patients who have been desensitized may participate.
- •Part C Only
- •History of interstitial lung disease or a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
- •History of immune mediated colitis, hepatitis, endocrinopathies, nephritis or significant immune mediated skin reactions such as toxic epidermal necrolitis or Stevens -Johnson Syndrome
- •History of any autoimmune disease which required systemic therapy* in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs) including but not limited to: i. Inflammatory bowel disease (including ulcerative colitis and Crohn's Disease) ii. Rheumatoid arthritis iii. Systemic progressive sclerosis (scleroderma) iv. Systemic lupus erythematosus v. Autoimmune vasculitis (e.g. Wegener's granulomatosis) *Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed)
- •Prior treatment with a checkpoint inhibitor (anti-PD-1, PD-L1, CTLA-4 etc.) within 4 weeks prior to the start of study drug
- •Prior treatment with a CD47-targeted therapy
- •Prior organ or stem cell transplant
研究组 & 干预措施
AO-176 Dose Escalation
Each dose escalation cohort will initially recruit 3 patients to receive AO-176 in a standard 3+3 design; cohorts will be expanded in the event of a DLT.
干预措施: AO-176 (Drug)
AO-176 Dose Expansion
Once the MTD/RP2D has been established, tumor-specific dose expansion cohorts will be recruited to further assess safety and evaluate preliminary efficacy of AO-176.
干预措施: AO-176 (Drug)
AO-176 + Paclitaxel Dose Escalation
Each dose escalation cohort will initially recruit 3 patients to receive AO-176 and paclitaxel in a standard 3+3 design; cohorts will be expanded in the event of a DLT.
干预措施: AO-176 + Paclitaxel (Drug)
AO-176 + Paclitaxel Dose Expansion
Once the MTD/RP2D has been established, tumor-specific dose expansion cohorts will be recruited to further assess safety and evaluate preliminary efficacy of AO-176 + paclitaxel.
干预措施: AO-176 + Paclitaxel (Drug)
AO-176 + Pembrolizumab Dose Escalation
Each dose escalation cohort will initially recruit 3 patients to receive AO-176 and pembrolizumab in a standard 3+3 design; cohorts will be expanded in the event of a DLT.
干预措施: AO-176 + Pembrolizumab (Drug)
AO-176 + Pembrolizumab Dose Expansion
Once the MTD/RP2D has been established, tumor-specific dose expansion cohorts will be recruited to further assess safety and evaluate preliminary efficacy of AO-176 + pembrolizumab.
干预措施: AO-176 + Pembrolizumab (Drug)
结局指标
主要结局
Safety of AO-176 assessed by adverse events and laboratory abnormalities
时间窗: Up to 12 months
Evaluate the safety of AO-176 measured by the number adverse events, serious adverse events and lab abnormalities.
Safety of AO-176 and paclitaxel assessed by adverse events and laboratory abnormalities
时间窗: Up to 12 months
Evaluate the safety of AO-176 in combination with paclitaxel measured by the number adverse events, serious adverse events and lab abnormalities.
Safety of AO-176 and pembrolizumab assessed by adverse events and laboratory abnormalities
时间窗: Up to 12 months
Evaluate the safety of AO-176 in combination with pembrolizumab measured by the number adverse events, serious adverse events and lab abnormalities.
次要结局
- AO-176 anti-tumor activity assessed by changes in response criteria(Up to 12 months)
- AO-176 + paclitaxel anti-tumor activity assessed by changes in response criteria(Up to 12 months)
- AO-176 + pembrolizumab anti-tumor activity assessed by changes in response criteria(Up to 12 months)