A Phase I/II, Open-Label, Multi-Center Study of ALE.C04 as a Single Agent and in Combination With Pembrolizumab in Adult Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 21
- 试验地点
- 22
- 主要终点
- Incidence of Dose Limiting Toxicity (DLT)
研究概览
简要总结
The purpose of this study is to evaluate the safety profile of ALE.C04 monotherapy and in combination with pembrolizumab, to characterize pharmacokinetics profile of ALE.C04, recommended Phase II dose (RP2D) for ALE.C04 in combination with pembrolizumab and as monotherapy and to assess anti-tumor activity of ALE.C04 monotherapy and in combination with pembrolizumab in patients with Head and Neck Cancer.
详细描述
The study comprises a phase I and a phase II. The phase I dose escalation part for both ALE.C04 monotherapy and in combination with pembrolizumab and a recommended dose for expansion (RDE) part for both ALE.C04 monotherapy and in combination with pembrolizumab. The phase II comprises a 1:1 randomized 2 arms assessing 2 dose levels of ALE.C04 as monotherapy and a 1:1 randomized 2 arms assessing ALE.C04 and pembrolizumab given in combination versus pembrolizumab monotherapy
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
盲法说明
Open Label
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
- •Be willing and able to provide written informed consents
- •Be 18 years of age on day of signing informed consent.
- •Have histologically or cytologically confirmed Recurrent or Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC) that is considered incurable by local therapies.
- •Have provided tissue for claudin-1 (CLDN1), programmed death ligand-1 (PD-L1) and biomarker analysis in a central Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.
- •Have measurable disease based on RECIST 1.1 as determined by the site.
- •Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
- •Have results from testing of human papillomavirus (HPV) status for oropharyngeal cancer
排除标准
- •Has progressive disease (PD) within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC (Phase II randomized combination part only).
- •Has had radiation therapy (or other non-systemic therapy) within 2 weeks prior to randomization or patient has not fully recovered (i.e., ≤Grade 1 or at baseline) from adverse events due to a previously administered treatment. Palliative radiotherapy to a limited field is allowed.
- •Severe immune-related adverse events leading to discontinuation of prior immune-oncology agent only for Phase I dose escalation monotherapy and combination and Phase II monotherapy.
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Dermatological conditions requiring active pharmacological treatment including psoriasis, atopic dermatitis, excessively dry skin or recurrent conjunctivitis, scleroderma, vitiligo, or any other active autoimmune dermatological disorder.
- •Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the clinical study, interfere with the patient's participation for the full duration of the clinical study, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
- •Has received prior therapy with an anti-programmed death (PD)-1, anti-PD-L1 or anti-PD-L2 (Phase II randomized combination part only).
研究组 & 干预措施
Phase 1 Recommended Dose for Expansion
Two ALE.C04 dose levels (higher or lower) will be considered for the combination with pembrolizumab
干预措施: ALE.C04 (Drug)
Phase 1 Recommended Dose for Expansion
Two ALE.C04 dose levels (higher or lower) will be considered for the combination with pembrolizumab
干预措施: Pembrolizumab (Drug)
Phase 1 Dose Escalation
ALE.C04 single agent: Three planned doses of ALE.C04 and ALE.C04 in combination with pembrolizumab. Once a certain dose level of ALE.C04 is considered safe and well tolerated, the first cohort of patients receiving ALE.C04 at a lower dose level combined with pembrolizumab will be initiated
干预措施: ALE.C04 (Drug)
Phase 1 Dose Escalation
ALE.C04 single agent: Three planned doses of ALE.C04 and ALE.C04 in combination with pembrolizumab. Once a certain dose level of ALE.C04 is considered safe and well tolerated, the first cohort of patients receiving ALE.C04 at a lower dose level combined with pembrolizumab will be initiated
干预措施: Pembrolizumab (Drug)
Phase 2 Randomized Combination part
ALE.C04 at RP2D combined to pembrolizumab compared to pembrolizumab monotherapy
干预措施: ALE.C04 (Drug)
Phase 2 Randomized Combination part
ALE.C04 at RP2D combined to pembrolizumab compared to pembrolizumab monotherapy
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Incidence of Dose Limiting Toxicity (DLT)
时间窗: 21 days
Phase I dose escalation
Confirmed Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) assessment according to RECIST1.1
时间窗: Up to 4.5 year
Time from start of study treatment to first documentation of objective progressive disease (PD) as per RECIST1.1 or to death due to any causes whichever come first during phase II
Incidence and severity of adverse events (AEs), serious adverse events (SAEs)
时间窗: Up to 30 days after last dose - Approximately 4.5 years
Descriptive statistics will be used to summarize results
Confirmed Objective Response Rate (ORR) by investigators assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
时间窗: Up to 4.5 year
Proportion of patients with confirmed Complete Response (CR) or Partial Response (PR) according to RECIST 1.1 for Phase II
次要结局
- Maximum serum concentration (Cmax) pharmacokinetics (PK) of ALE.C04(up to 4.5 years)
- Area under the concentration-time curve (AUC) pharmacokinetics (PK) of ALE.C04(up to 4.5 years)
- Immune Duration Of Response (iDOR)(up to 4.5 years)
- Immune Progression Free Survival (iPFS) evaluated by investigators(up to 4.5 years)
- Overall Survival (OS)(up to 4.5 years)
- Minimum serum concentration (Cmin) pharmacokinetics (PK) of ALE.C04(up to 4.5 years)
- Change from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30(Phase II combination part only - Up to 4.5 year)
- Confirmed ORR by investigators assessment according to RECIST1.1(up to 4.5 year)
- Maximum serum concentration (Cmax) Pharmacokinetics (PK) of pembrolizumab(up to 4.5 years)
- Minimum serum concentration (Cmin) Pharmacokinetics (PK) of pembrolizumab(up to 4.5 years)
- Area under the concentration-time curve (AUC) Pharmacokinetics (PK) of pembrolizumab(up to 4.5 years)
- Immunogenicity of ALE.C04(up to 4.5 years)
- Disease Control Rate (DCR) as per investigator assessment according to RECIST1.1(up to 4.5 years)
- Immune Disease Control Rate (iDCR) as per investigator assessment according to immune RECIST(up to 4.5 years)
- Duration Of Response (DOR)(up to 4.5 years)
- Confirmed immune Objective Response Rate (iORR) by investigators assessment according to immune RECIST(up to 4.5 year)
- Progression Free Survival (PFS) evaluated by investigators(up to 4.5 years)
- Change from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Question Head and Neck module 43 (HN43)(Phase II combination part only - Up to 4.5 year)