An Open-Label, Phase II, Randomized, Controlled Study of Danvatirsen Plus Pembrolizumab Compared to Pembrolizumab Alone in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 69
- 试验地点
- 32
- 主要终点
- Confirmed ORR
研究概览
简要总结
Open-label, Phase II, randomized, controlled study evaluating the efficacy and safety of danvatirsen in combination with pembrolizumab compared with pembrolizumab alone as first-line treatment of patients with recurrent/metastatic (R/M) HNSCC. Two-thirds of patients will be randomized to receive danvatirsen and pembrolizumab and one-third will be randomized to receive pembrolizumab alone.
详细描述
This is a multicenter, open-label, Phase II, randomized, controlled study to determine the efficacy, safety, and other indicators of clinical and biological activity of the combination of danvatirsen and pembrolizumab as first-line treatment for R/M HNSCC.
After providing informed consent, patients will be assessed for eligibility during the screening phase of the study. All patients must be willing and able to provide a formalin fixed paraffin-embedded (FFPE) archival or fresh tumor sample collected during the screening period; a fresh biopsy is preferred if safe and feasible to obtain and consented to by the patient. Following the screening period, eligible patients will be randomized in a 2:1 ratio to danvatirsen + pembrolizumab or pembrolizumab monotherapy, respectively. Patients will receive treatment in 21-day cycles. Patients assigned to the pembrolizumab monotherapy arm will receive treatment until a criterion for discontinuation is met or a maximum of 24 months of treatment. Patients assigned to combination therapy will receive both treatments until a criterion for discontinuation is met or the patient has received a maximum of 24 months of treatment, after which they may remain on danvatirsen monotherapy.
Patients in both treatment arms will have radiologic tumor assessments every 6 weeks (±1 week), regardless of treatment delays, until objective disease progression, initiation of new anticancer treatment, death, withdrawal of consent, or end of study, whichever occurs first.
All patients who discontinue study treatment for any reason will have a safety follow-up visit 30 days (+7 days) after the last dose of study treatment and a follow-up for AEs 90 days (+7 days) after the last dose of pembrolizumab. Patients will be followed for survival at 12 week (±7 days) intervals until death or withdrawal of consent, whichever occurs first. Survival follow-up will continue until at least 15 months after the last patient is randomized in the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Must have given written informed consent (signed and dated).
- •Aged ≥18 years at the time of informed consent.
- •Recurrent/metastatic histologically or cytologically proven squamous cell carcinoma of the head and neck that is considered incurable by local therapy. Eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.
- •Presence of measurable tumor per RECIST v1.1 criteria.
- •Detectable PD-L1 expression in tumor, defined as CPS ≥1 determined by a FDA or national regulatory agency of the country in which the patient resides.-approved test.
- •Baseline fresh tumor biopsy or archival specimen.
- •ECOG performance status of 0 or
- •Adequate organ function within 10 days of study treatment,
- •Oxygen saturation on room air ≥92% by pulse oximetry.
- •Females must be non-pregnant and non-lactating and either be postmenopausal or agree to adequate birth control.
- •Males must be surgically sterile or agree to adequate birth control.
- •Has an estimated life expectancy of at least 3 months.
- •Has recovered from all complications or surgery and all toxicities of prior therapy
排除标准
- •Prior therapy for metastatic HNSCC.
- •Has disease suitable for local therapy with curative intent.
- •Primary tumor of the nasopharynx.
- •Has received prior therapy with an anti-programmed death 1 (PD-1), anti PD L1, or anti-programmed death-ligand-2 (PD-L2).
- •Radiation therapy (or other non-systemic therapy) within 2 weeks of Day 1 of study treatment.
- •Known autoimmune disease that has required systemic treatment
- •Known immunodeficiency or receiving systemic steroid therapy that would be the equivalent of >10 mg prednisone daily
- •Prior allogeneic tissue/solid organ transplant.
- •Has significant cardiovascular disease
- •Has received a live vaccine within 30 days
- •Active infection requiring systemic antiviral or antimicrobial therapy
- •History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
- •History of other malignancies
- •Active HIV infection except patients who are currently stable on antiretroviral therapy for at least 4 weeks
- •Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
- •Treated or untreated parenchymal brain metastases or leptomeningeal disease.
- •Treatment with another investigational drug, biological agent, or device within 1 month of screening, or 5 half-lives of investigational agent (if known), whichever is longer.
- •Hypersensitivity to any component of danvatirsen or pembrolizumab.
研究组 & 干预措施
Danvatirsen plus pembrolizumab
Danvatirsen dosing:
Week 1: Danvatirsen intravenously (IV) on Days 1, 3, and 5
Week 2 and subsequent weeks: Danvatirsen IV weekly
Pembrolizumab dosing:
Pembrolizumab every 3 weeks after the Danvatirsen dose.
干预措施: Danvatirsen (Drug)
Danvatirsen plus pembrolizumab
Danvatirsen dosing:
Week 1: Danvatirsen intravenously (IV) on Days 1, 3, and 5
Week 2 and subsequent weeks: Danvatirsen IV weekly
Pembrolizumab dosing:
Pembrolizumab every 3 weeks after the Danvatirsen dose.
干预措施: Pembrolizumab (Drug)
Pembrolizumab
Pembrolizumab IV every 3 weeks
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Confirmed ORR
时间窗: Up to 18 months
Determine the ORR (Partial response \[PR\] + CR defined according to RECIST v1.1) as determined by the Investigator for the combination of danvatirsen and pembrolizumab compared with pembrolizumab alone
次要结局
- DCR & CR Rate(Up to 18months)
- OS(Up to 30months)
- DOR(Up to 18months)
- PFS(Up to 18months)
- Number of Participants With Adverse Events as Assessed by CTCAE v5.0(Up to 18 months)
- ORR in Tumors With CPS ≥20 and ≥ 50(Up to 18months)
- DOR in Tumors With CPS ≥20 and ≥50(Up to 18months)
- Maximum Plasma Concentration(Up to 18 months)
- Trough Concentration(Up to 18 months)
- Area Under the Plasma Concentration-time Curve(Up to 18 months)
- Time to Maximum Plasma Concentration(Up to 18 months)
- Immunogenicity of Danvatirsen(Up to 18 months)