Clinical trial · Interventional
APG-157 in Locally Advanced Head and Neck Squamous Cell Carcinoma
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
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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).
Conditions
Conditions (7)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Head and Neck Cancer | Malignant Head and Neck Neoplasm | ALIAS | 0.90 |
| Head and Neck (HNSCC) | Head and Neck Squamous Cell Carcinoma | ALIAS | 0.85 |
| Oral Cavity | — | UNRESOLVED | — |
| Oral Cavity Carcinoma | Oral Cavity Carcinoma | ONTOLOGY_EXACT | 0.98 |
| Oral Cavity Squamous Cell Carcinoma | Oral Cavity Squamous Cell Carcinoma | ONTOLOGY_EXACT | 0.98 |
| Oropharyngeal | — | UNRESOLVED | — |
| Oropharynx Squamous Cell Carcinoma | Oropharynx Squamous Cell Carcinoma | ONTOLOGY_EXACT | 0.98 |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| APG-157 | Drug | — | UNRESOLVED |
| Radiation/Chemotherapy | Radiation | — | UNRESOLVED |
| Surgery | Procedure | — | UNRESOLVED |
Design
Arms and outcomes
Arms (4)
- type
- EXPERIMENTAL
- label
- Cohort A - APG-157
- description
- 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.
- interventionNames
- Drug: APG-157
- Procedure: Surgery
- Radiation: Radiation/Chemotherapy
- type
- ACTIVE_COMPARATOR
- label
- Cohort A - Control
- description
- Standard-of-care surgery and adjuvant therapy; Participants undergo curative-intent surgery followed by protocol-directed adjuvant therapy
- interventionNames
- Procedure: Surgery
- Radiation: Radiation/Chemotherapy
- type
- EXPERIMENTAL
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria Cohort A (Resectable Disease) 1. Adults ≥18 years 2. Histologically or cytologically confirmed, previously untreated locally advanced head and neck squamous cell carcinoma (LA-HNSCC) of the oral cavity or oropharynx. 3. Resectable disease appropriate for curative-intent surgery. 4. 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) 5. Objectively medically ineligible for perioperative pembrolizumab according to protocol-defined objective criteria. 6. HPV/p16 testing available for stratification. 7. Measurable or evaluable disease. 8. Life expectancy ≥12 months. 9. ECOG Performance Status ≤2. 10. Negative pregnancy test for women of childbearing potential and agreement to use effective contraception. 11. Ability to comply with study procedures. Cohort B (Unresectable / Medically Inoperable Disease) 1. Adults ≥18 years 2. Histologically or cytologically confirmed, previously untreated LA-HNSCC of the oropharynx. Disease not suitable for curative-intent surgery. 3. 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) 4. HPV/p16 testing available for stratification. 5. Presence of evaluable tumor burden. 6. Eligible to receive definitive chemoradiotherapy. 7. Life expectancy ≥12 months. 8. ECOG Performance Status ≤2. 9. Adequate organ function. 10. Contraception requirements met. 11. 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.
References
Publications (0)
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