APG-157 in Locally Advanced Head and Neck Squamous Cell Carcinoma

NCT07667296 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: AVTA30-01
• Study Type: interventional
• Target: 826
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Head and Neck Cancer; Head and Neck (HNSCC); Oropharyngeal; Oral Cavity; Oral Cavity Carcinoma; Oropharynx Squamous Cell Carcinoma; Oral Cavity Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Event-Free Survival (EFS)

  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.

Secondary Outcomes (10)

• Overall Survival (OS)

  Time from randomization until death from any cause; assessed up to approximately 60 months.

• Objective Response Rate (ORR)

  • Cohort A: Week 6 and pre-surgery assessment • Cohort B: Week 4 and pre-CRT assessment

• ctDNA Clearance Rate

  Baseline through protocol-defined follow-up assessments up to approximately 36 months.

• Clinically Meaningful Pathological Response(Cohort A):

  At definitive surgery (approximately 6-9 weeks after randomization).

• Major Pathologic Response (MPR) (Cohort A)

  At definitive surgery.

Study Arms (4)

Cohort A - APG-157

EXPERIMENTAL

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.

Drug: APG-157; Procedure: Surgery; Radiation: Radiation/Chemotherapy

Cohort A - Control

ACTIVE COMPARATOR

Standard-of-care surgery and adjuvant therapy; Participants undergo curative-intent surgery followed by protocol-directed adjuvant therapy

Procedure: Surgery; Radiation: Radiation/Chemotherapy

Cohort B - APG-157

EXPERIMENTAL

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

Drug: APG-157; Radiation: Radiation/Chemotherapy

Cohort B - Control

ACTIVE COMPARATOR

Standard-of-Care Chemoradiotherapy. Participants receive definitive upfront chemoradiotherapy

Radiation: Radiation/Chemotherapy

Interventions

APG-157 DRUG

APG-157 is a first-in-class investigational drug product, formulated as 100 mg soft hydrogel pastille to dissolve in the mouth

Cohort A - APG-157; Cohort B - APG-157

Surgery PROCEDURE

Definitive Surgery

Cohort A - APG-157; Cohort A - Control

Radiation/Chemotherapy RADIATION

Protocol-specified risk-adapted postoperative radiotherapy, with concurrent platinum-based chemotherapy (e.g., cisplatin or carboplatin) administered when indicated based on pathological risk factors

Cohort A - APG-157; Cohort A - Control; Cohort B - APG-157

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Aveta Biomics, Inc.: lead

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck; Mouth Neoplasms

Interventions

Surgical Procedures, Operative; Radiation; Drug Therapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Physical Phenomena; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: June 8, 2026
• First Posted: June 25, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): December 1, 2031
• Study Completion (Estimated): December 1, 2032
• Last Updated: July 1, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share