New pastille could change head and neck cancer treatment

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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.