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Head and Neck CancerPhase 3NCT07667296

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

A Phase 3 study testing APG-157, Surgery and Radiation/Chemotherapy in people with Head and Neck Cancer and Head and Neck (HNSCC), run by Aveta Biomics, Inc..

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
APG-157, Surgery and Radiation/Chemotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
826 participants
Where
No sites listed yet
Study dates
Jul 2026to Dec 2032
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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.

Who cannot join

  • Cohort A Specific:
  • Stage I-II disease
  • Stage IVb or Ivc disease
  • T4b unresectable disease
  • N3 disease where applicable
  • Medically eligible for perioperative pembrolizumab
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  • 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.

About this study

Official title: 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).

Read the detailed description

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.

Being tested
APG-157, Surgery, Radiation/Chemotherapy
Medical subject headings
Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck, Mouth Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • APG-157Drug

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

  • SurgeryProcedure or surgery

    Definitive Surgery

  • Radiation/ChemotherapyRadiation

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

  • Radiation/ChemotherapyRadiation

    Definitive radiotherapy with concurrent protocol-specified platinum-based chemotherapy.

Study groups in NCT07667296
Study groupRoleWhat they receive
Cohort A - APG-157ExperimentalAPG-157 600 mg/day (200 mg orally three times daily)for 6 weeks prior to curative-intent surgery followed by protocol-directed adjuvant therapy.
Receives: Drug: APG-157; Procedure: Surgery; Radiation: Radiation/Chemotherapy
Cohort A - ControlActive comparatorStandard-of-care surgery and adjuvant therapy; Participants undergo curative-intent surgery followed by protocol-directed adjuvant therapy
Receives: Procedure: Surgery; Radiation: Radiation/Chemotherapy
Cohort B - APG-157ExperimentalAPG-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
Receives: Drug: APG-157; Radiation: Radiation/Chemotherapy
Cohort B - ControlActive comparatorStandard-of-Care Chemoradiotherapy. Participants receive definitive upfront chemoradiotherapy
Receives: Radiation: Radiation/Chemotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)
  1. Overall Survival (OS)

    Overall survival is defined as the time from randomization until death from any cause.

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

  2. Objective Response Rate (ORR)

    Proportion of participants achieving confirmed response (CR) or partial response (PR) according to RECIST v1.1 as assessed by BICR.

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

  3. ctDNA Clearance Rate

    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.

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

  4. Clinically Meaningful Pathological Response(Cohort A):

    Proportion of participants achieving ≤50% residual viable tumor in the resected specimen as assessed by BICR.

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

  5. Major Pathologic Response (MPR) (Cohort A)

    Proportion of participants achieving ≤10% residual viable tumor in the resected specimen as assessed by BICR.

    Measured: At definitive surgery.

  6. Composite Pathologic Response (Cohort A)

    Composite assessment including:

    • Pathologic tumor response category
    • Surgical margin status
    • Extranodal extension status
    • Clinical-to-pathologic downstaging

    Measured: At definitive surgery.

  7. Incidence of Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Treatment Discontinuations Due to Adverse Events

    Measured: From first dose through 30 days after last study treatment.

  8. Patient-Reported Outcomes

    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.

    Measured: Baseline through approximately 36 months.

  9. Patient-Report Outcomes

    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.

    Measured: Baseline through approximately 36 months

  10. Ability to Initiate Definitive Therapy

    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))

    Measured: Up to 21 days after last dose of APG-157

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jun 2026
  2. Study startJul 2026 (estimated)
  3. Primary completionDec 2031 (estimated)
  4. Study completionDec 2032 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
826 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07667296
Sponsor's protocol ID
AVTA30-01
Status last verified
Jun 2026
First submitted
8 Jun 2026
Last updated
1 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: 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.
Expanded access
Available

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing APG-157, Surgery and Radiation/Chemotherapy in people with Head and Neck Cancer and Head and Neck (HNSCC), run by Aveta Biomics, Inc..

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 1 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-Free Survival (EFS) (time frame: 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2026.

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