APG-157 in Locally Advanced Head and Neck Squamous Cell Carcinoma
2026年6月29日 更新者：Aveta Biomics, Inc.
A Multicenter, Randomized, Open-Label Phase 3 Study of APG-157 as Neoadjuvant Therapy or as Induction and Maintenance Therapy in Locally Advanced Head and Neck Squamous Cell Carcinoma
This Phase 3, multicenter, randomized, open-label study evaluates APG-157 in adults with newly diagnosed locally advanced head and neck squamous cell carcinoma (LA-HNSCC).
Two independently powered cohorts are enrolled based on treatment pathway.
Cohort A evaluates APG-157 administered as neoadjuvant therapy before curative-intent surgery in participants with resectable oral cavity or oropharyngeal cancer who are medically ineligible for perioperative pembrolizumab.
Cohort B evaluates APG-157 administered as induction therapy before definitive chemoradiotherapy and as maintenance therapy after chemoradiotherapy in participants with unresectable or medically inoperable disease.
Participants are randomized 1:1 within each cohort to receive APG-157-based treatment or standard-of-care therapy.
The primary hypothesis is that APG-157 given before definitive surgery followed by (chemo)radiotherapy improves event-free survival (EFS) compared to surgery and adjuvant (chemo)radiotherapy alone (Cohort A), and that APG-157 given as induction therapy prior to definitive chemoradiotherapy (CRT) followed by maintenance APG-157 improves EFS compared to definitive CRT alone (Cohort B).
研究概览
地位
尚未招聘
详细说明
This Phase 3, multicenter, randomized, open-label study evaluates APG-157 in adults with newly diagnosed locally advanced head and neck squamous cell carcinoma (LA-HNSCC).
The study consists of two independently powered cohorts designed to evaluate APG-157 in distinct treatment settings.
Cohort A enrolls participants with resectable oral cavity or oropharyngeal squamous cell carcinoma who are objectively medically ineligible for perioperative pembrolizumab according to protocol-defined criteria.
Participants are randomized 1:1 to receive APG-157 administered orally at 600 mg/day for 6 weeks prior to curative-intent surgical resection followed by protocol-directed adjuvant therapy, or standard-of-care surgery followed by adjuvant therapy alone.
Cohort B enrolls participants with unresectable or medically inoperable locally advanced oropharyngeal squamous cell carcinoma.
Participants are randomized 1:1 to receive APG-157 induction therapy for 4 weeks before definitive chemoradiotherapy, followed by APG-157 maintenance therapy initiated within 60 days after chemoradiotherapy and continued for up to 1 year, or standard-of-care definitive chemoradiotherapy alone.The primary objective is to determine whether APG-157-based treatment improves event-free survival compared with standard-of-care treatment.
Key secondary objectives include overall survival, objective response, pathological response, ctDNA clearance, safety, treatment feasibility, and patient-reported outcomes.
研究类型
介入性
注册 (估计的)
826
阶段
- 第三阶段
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
不
描述
Inclusion Criteria
Cohort A (Resectable Disease)
- Adults ≥18 years
- Histologically or cytologically confirmed, previously untreated locally advanced head and neck squamous cell carcinoma (LA-HNSCC) of the oral cavity or oropharynx.
- Resectable disease appropriate for curative-intent surgery.
Stage III-IVA disease according to AJCC criteria:
- Oropharynx, p16-positive: Stage III (T4, N0-N3, M0)
- Oropharynx, p16-negative: Stage III or IVa (T3-T4, N0-N2, M0)
- Oral cavity: Stage III or IVa (T3-T4, N0-N2, M0)
- Objectively medically ineligible for perioperative pembrolizumab according to protocol-defined objective criteria.
- HPV/p16 testing available for stratification.
- Measurable or evaluable disease.
- Life expectancy ≥12 months.
- ECOG Performance Status ≤2.
- Negative pregnancy test for women of childbearing potential and agreement to use effective contraception.
- Ability to comply with study procedures.
Cohort B (Unresectable / Medically Inoperable Disease)
- Adults ≥18 years
- Histologically or cytologically confirmed, previously untreated LA-HNSCC of the oropharynx. Disease not suitable for curative-intent surgery.
Stage III-IVA disease according to AJCC criteria:
- p16-positive Stage III (T4, N0-N3, M0) with >10 pack-year smoking history
- p16-negative Stage III or IVa (T3-T4, N0-N2, M0)
- HPV/p16 testing available for stratification.
- Presence of evaluable tumor burden.
- Eligible to receive definitive chemoradiotherapy.
- Life expectancy ≥12 months.
- ECOG Performance Status ≤2.
- Adequate organ function.
- Contraception requirements met.
- Ability to comply with study procedures.
Exclusion Criteria
Cohort A Specific:
- Stage I-II disease
- Stage IVb or Ivc disease
- T4b unresectable disease
- N3 disease where applicable
- Medically eligible for perioperative pembrolizumab
Cohort B Specific:
- Stage I-II disease
- Disease not appropriate for curative-intent CRT
- Active autoimmune disease requiring systemic therapy
- Prior solid organ or allogeneic stem cell transplant
- Ongoing immunosuppression >10 mg/day prednisone equivalent
Common Exclusion Criteria:
- Primary tumor arising from the nasopharynx, hypopharynx, larynx, paranasal sinus, or unknown primary site.
- Prior treatment for current head and neck squamous cell carcinoma.
- Prior malignancy unless protocol exceptions met
- Distant metastatic disease
- Live vaccine within 30 days
- Known hypersensitivity to APG-157 or its components.
- Unresolved clinically significant toxicity
- Recent participation in another investigational study
- Active uncontrolled infection
- Significant uncontrolled cardiovascular disease
- Pregnancy or breastfeeding.
- QTcF >500 msec or congenital long QT syndrome
- Any condition compromising safety, compliance, or study interpretation
Randomization ratio: 1:1 within each cohort
Stratification Factors:
Cohort A:
- HPV/p16 status,
- Planned platinum strategy,
- PD-L1 CPS category
Cohort B:
- HPV/p16 status
- Planned platinum strategy
- Geographic region.
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：Cohort A - APG-157
APG-157 600 mg/day (200 mg orally three times daily)for 6 weeks prior to curative-intent surgery followed by protocol-directed adjuvant therapy.
|
APG-157 is a first-in-class investigational drug product, formulated as 100 mg soft hydrogel pastille to dissolve in the mouth
Definitive Surgery
Protocol-specified risk-adapted postoperative radiotherapy, with concurrent platinum-based chemotherapy (e.g., cisplatin or carboplatin) administered when indicated based on pathological risk factors
Definitive radiotherapy with concurrent protocol-specified platinum-based chemotherapy.
|
|
有源比较器：Cohort A - Control
Standard-of-care surgery and adjuvant therapy; Participants undergo curative-intent surgery followed by protocol-directed adjuvant therapy
|
Definitive Surgery
Protocol-specified risk-adapted postoperative radiotherapy, with concurrent platinum-based chemotherapy (e.g., cisplatin or carboplatin) administered when indicated based on pathological risk factors
Definitive radiotherapy with concurrent protocol-specified platinum-based chemotherapy.
|
|
实验性的：Cohort B - APG-157
APG-157 induction therapy and standard-of-care definitive chemoradiotherapy followed by APG-157 maintenance therapy.
Participants receive APG-157 600 mg/day for 4 weeks (200 mg orally three times daily) prior to definitive chemoradiotherapy, followed by APG-157 maintenance therapy for up to 1 year
|
APG-157 is a first-in-class investigational drug product, formulated as 100 mg soft hydrogel pastille to dissolve in the mouth
Protocol-specified risk-adapted postoperative radiotherapy, with concurrent platinum-based chemotherapy (e.g., cisplatin or carboplatin) administered when indicated based on pathological risk factors
Definitive radiotherapy with concurrent protocol-specified platinum-based chemotherapy.
|
|
有源比较器：Cohort B - Control
Standard-of-Care Chemoradiotherapy.
Participants receive definitive upfront chemoradiotherapy
|
Protocol-specified risk-adapted postoperative radiotherapy, with concurrent platinum-based chemotherapy (e.g., cisplatin or carboplatin) administered when indicated based on pathological risk factors
Definitive radiotherapy with concurrent protocol-specified platinum-based chemotherapy.
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Event-Free Survival (EFS)
大体时间：From randomization until the first occurrence of a protocol-defined EFS event, death, withdrawal from study follow-up, or study completion, assessed for up to approximately 36 months.
|
EFS is defined as the time from randomization to the earliest occurrence of a protocol-defined EFS event, including radiographic and/or clinical disease progression that precludes initiation or completion of planned definitive curative-intent therapy; locoregional recurrence, progression, or distant metastasis following definitive treatment, confirmed by imaging, pathology, salvage intervention with viable tumor or other protocol-defined assessments, where applicable, or death from any cause. EFS will be analyzed by blinded independent central review (BICR) using RECIST v1.1 and protocol-defined pathology criteria, as applicable. The primary analysis will be conducted in the intent-to-Treat ( ITT) population using stratified log-rank testing and Cox proportional hazards models. |
From randomization until the first occurrence of a protocol-defined EFS event, death, withdrawal from study follow-up, or study completion, assessed for up to approximately 36 months.
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Overall Survival (OS)
大体时间：Time from randomization until death from any cause; assessed up to approximately 60 months.
|
Overall survival is defined as the time from randomization until death from any cause.
|
Time from randomization until death from any cause; assessed up to approximately 60 months.
|
|
Objective Response Rate (ORR)
大体时间：• Cohort A: Week 6 and pre-surgery assessment • Cohort B: Week 4 and pre-CRT assessment
|
Proportion of participants achieving confirmed response (CR) or partial response (PR) according to RECIST v1.1 as assessed by BICR.
|
• Cohort A: Week 6 and pre-surgery assessment • Cohort B: Week 4 and pre-CRT assessment
|
|
ctDNA Clearance Rate
大体时间：Baseline through protocol-defined follow-up assessments up to approximately 36 months.
|
Change in circulating tumor DNA (ctDNA) levels over time and proportion of participants achieving ctDNA clearance from the baseline assessed using a tumor-informed assay.
|
Baseline through protocol-defined follow-up assessments up to approximately 36 months.
|
|
Clinically Meaningful Pathological Response(Cohort A):
大体时间：At definitive surgery (approximately 6-9 weeks after randomization).
|
Proportion of participants achieving ≤50% residual viable tumor in the resected specimen as assessed by BICR.
|
At definitive surgery (approximately 6-9 weeks after randomization).
|
|
Major Pathologic Response (MPR) (Cohort A)
大体时间：At definitive surgery.
|
Proportion of participants achieving ≤10% residual viable tumor in the resected specimen as assessed by BICR.
|
At definitive surgery.
|
|
Composite Pathologic Response (Cohort A)
大体时间：At definitive surgery.
|
Composite assessment including:
|
At definitive surgery.
|
|
Incidence of Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Treatment Discontinuations Due to Adverse Events
大体时间：From first dose through 30 days after last study treatment.
|
From first dose through 30 days after last study treatment.
|
|
|
Ability to Initiate Definitive Therapy
大体时间：Up to 21 days after last dose of APG-157
|
Proportion of participants able to initiate protocol-defined definitive curative-intent therapy within protocol-specified timing windows (Within 21 days after the last dose of APG-157 prior to definitive surgery (Cohort A) or definitive chemoradiotherapy (Cohort B))
|
Up to 21 days after last dose of APG-157
|
|
Patient-Reported Outcomes
大体时间：Baseline through approximately 36 months.
|
EuroQol-5 Dimension, 5-Level (EQ-5D-5L).
Change from baseline in the EQ-5D-5L Health Utility Index score.
The Health Utility Index is derived from responses to the five EQ-5D-5L dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) using a country-specific value set.
Scores typically range from less than 0 (health states considered worse than death) to 1.0 (full health), with higher scores indicating better health-related quality of life.
|
Baseline through approximately 36 months.
|
|
Patient-Report Outcomes
大体时间：Baseline through approximately 36 months
|
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30).
Change from baseline in the EORTC QLQ-C30 Global Health Status/Quality of Life Scale score.
The Global Health Status/Quality of Life Scale is transformed to a 0 to 100 scale, with higher scores indicating better global health status and quality of life.
|
Baseline through approximately 36 months
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (估计的)
2026年7月1日
初级完成 (估计的)
2031年12月1日
研究完成 (估计的)
2032年12月1日
研究注册日期
首次提交
2026年6月8日
首先提交符合 QC 标准的
2026年6月22日
首次发布 (实际的)
2026年6月25日
研究记录更新
最后更新发布 (实际的)
2026年7月1日
上次提交的符合 QC 标准的更新
2026年6月29日
最后验证
2026年6月1日
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- AVTA30-01
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
不
IPD 计划说明
The sponsor does not currently plan to make individual participant data available to researchers outside the study sponsor and its designated representatives.
Study results will be made publicly available through ClinicalTrials.gov
and scientific publications as appropriate.
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是的
研究美国 FDA 监管的设备产品
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