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).
調査の概要
状態
まだ募集していません
詳細な説明
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.
研究の種類
介入
入学 (推定)
826
段階
- フェーズ 3
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
いいえ
説明
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.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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.
|
|
アクティブコンパレータ：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.
|
|
実験的：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.
|
|
アクティブコンパレータ：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.
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Event-Free Survival (EFS)
時間枠：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.
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Overall Survival (OS)
時間枠：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)
時間枠：• 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
時間枠：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):
時間枠：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)
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
|
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スポンサー
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (推定)
2026年7月1日
一次修了 (推定)
2031年12月1日
研究の完了 (推定)
2032年12月1日
試験登録日
最初に提出
2026年6月8日
QC基準を満たした最初の提出物
2026年6月22日
最初の投稿 (実際)
2026年6月25日
学習記録の更新
投稿された最後の更新 (実際)
2026年7月1日
QC基準を満たした最後の更新が送信されました
2026年6月29日
最終確認日
2026年6月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- AVTA30-01
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
いいえ
IPD プランの説明
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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米国FDA規制医薬品の研究
はい
米国FDA規制機器製品の研究
いいえ
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