Cetuximab Plus Platinum and Taxane-based Chemotherapy, Followed by Avelumab and Cetuximab, as First-line Treatment for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) Patients With a PD-L1 Combined Positive Score (CPS)≥1≤19.

NCT06869473 | Recruiting Phase 2

• 2 other identifiers: AVEC-1192024-512053-24-00
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 8

Brief Summary

This phase II interventional clinical trial aims to evaluate whether combining cetuximab and avelumab, after three cycles of platinum and taxane-based chemotherapy, can improve treatment outcomes for patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) with a PD-L1 combined positive score (CPS) between 1 and 19. Specifically, the study seeks to determine if this approach can increase the 6-month progression-free survival (PFS) rate from 40% to 55%. The trial will include adult patients with confirmed R/M HNSCC, who have not previously received systemic therapy for their advanced disease. By testing this sequential treatment strategy, researchers hope to improve outcomes for this specific patient population, which has shown poorer responses to existing immunotherapy options compared to those with higher PD-L1 expression levels. Participants will first undergo an induction phase, consisting of three cycles of chemotherapy with paclitaxel, platinum (cisplatin or carboplatin), and cetuximab. After this initial treatment, they will move to a maintenance phase, where they will receive avelumab and cetuximab every two weeks until disease progression or the occurrence of unacceptable side effects. The study aims to answer several key questions: Can this treatment approach improve progression-free survival at 6 months? What impact does it have on overall survival, response rates, and the duration of response? Is this combination therapy safe and well-tolerated? In addition to the treatment itself, participants will be asked to provide blood and tumor tissue samples for translational research, helping scientists better understand how biomarkers influence treatment response. Regular follow-up assessments will also be conducted to monitor disease progression and overall health. By testing this innovative treatment sequence, researchers hope to bridge the gap between different PD-L1 subgroups, potentially offering a more effective and personalized approach for patients with R/M HNSCC.

Conditions

Head and Neck Squamous Cell Carcinoma (HNSCC); Recurrent Head and Neck Cancer; Metastatic Head and Neck Cancer

Keywords

Head and Neck Neoplasms; Squamous Cell Carcinoma; Cetuximab; Avelumab; Anti-EGFR Therapy; Platinum-Based Chemotherapy; Taxane-Based Chemotherapy; PD-L1 Combined Positive Score (CPS)

Outcome Measures

Primary Outcomes (1)

• 6-months (6m)-Progression Free Survival

  The increase of the 6-months (6m)-Progression Free Survival intended as the time from baseline until first evidence of disease progression or death, from 40% to 55% in PD-L1 CPS≥1≤19 R/M HNSCC patients.

  6-months from baseline

Secondary Outcomes (4)

• overall survival (OS)

  From date of enrollment until the date of first documented until the date of death from any cause, assessed up to 12 months from last subject in

• overall response rate (ORR)

  Up to 12 months

• safety of cetuximab plus platinum and taxane-based chemotherapy

  up to 12 months

• duration of response (DOR)

  Up to 12 months

Study Arms (1)

single-arm

EXPERIMENTAL

in-label induction therapy with three cycles of TPE (Paclitaxel, platinum-based compound, Cetuximab), followed, only in patients who are (partially or completely) responders and stable, by a maintenance therapy with the combination of AVEC (Avelumab, an anti-PD-L1 drug, plus Cetuximab, an anti-EGFR drug) extended until disease progression, unacceptable toxicity, or patient withdrawal.

Drug: Cetuximab/avelumab

Interventions

Cetuximab/avelumab DRUG

Study Maintenance therapy: AVEC (each cycle every 2 weeks) Cetuximab will be administered at 500 mg/m2 dose (as a 2-hour intravenous infusion) every 2 weeks until disease progression or unacceptable side effects. Cetuximab will be administered by IV infusion over 120 minutes. The initial dose should be given slowly and speed of infusion must not exceed 5 mg/min. Avelumab will be administered at 800 mg flat dose (as a 1-hour intravenous fusion) every 2 weeks until disease progression or unacceptable side effects.

single-arm

Eligibility Criteria

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

You may qualify if:

• Subjects able to sign the informed consent and ≥18 y-old.
• Histologically or cytologically confirmed diagnosis of HNSCC.
• Confirmed R/M HNSCC (i.e. oral cavity, oropharynx, larynx, hypopharynx) not suitable for curative loco-regional therapy.
• PD-L1 CPS≥1≤19 (assessment allowed either on primary and/or recurrent/metastatic site of disease).
• Measurable disease according to RECIST Criteria 1.1.6. Subjects should not have had prior systemic therapy administered in the R/M HNSCC setting.
• Systemic therapy that was completed more than 6 months prior to signing consent, if given as a part of multimodal curative treatment for locally advanced disease, is allowed.
• ECOG Performance Status (PS) 0-1. 9.Adequate bone marrow function: neutrophils ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, hemoglobin ≥ 9 g/dL.
• Adequate liver function: total bilirubin level \< 1.5 X Upper Limit of Normal (ULN) (except for known medical reason not interfering with liver function, such as Gilbert syndrome), AP, GGT \<3 x ULN and AST and ALT levels ≤ 2.5 × ULN.
• Adequate renal function: calculated or analyzed creatinine clearance ≥ 30 mL/min.
• Archival or fresh tissue of primary disease (i.e. T and/or N and/or M) OR recurrent/metastatic disease available at baseline (before starting TPE) (available as Formalin-Fixed Paraffin-Embedded - FFPE - or as unstained 10-20 slices).
• Participants have to provide peripheral blood samples (at least 8-10 mL stored in EDTA) according the timing described in the translational part of the current protocol.
• Palliative radiotherapy and/or surgery within 4 weeks before the study entry are allowed.
• Symptomatic peripheral neuropathy NCI-CTC v5.0 grade ≥ 2 and / or ototoxicity grade ≥ 2, (except for cases in which ototoxicity is due to trauma or tumor-related mechanical impairment) or creatinine clearance \< 60 mL/min are acceptable and they must be approached with carboplatin (instead of cisplatin) since the trial start.

You may not qualify if:

• Nasopharyngeal, salivary gland, nasal sinus, and non-melanoma skin cancers are not allowed.
• Life expectancy lower than 3 months according to the judgement of trial investigator is not allowed.
• Previous chemotherapy, or biological therapy (i.e. Cetuximab), or immunotherapy administered for R/M setting of HNSCC is not allowed.
• Diagnosis of immunodeficiency or subjects receiving systemic steroid therapy (\> 10 mg/day of prednisone or equivalent) or any other form of immunosuppressive therapy within 30 days prior to start of study treatment which cannot be interrupted.
• Known allergic/hypersensitivity reaction to investigational products or any component in their formulations.
• Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with type I diabetes, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
• Any diagnosed and/or treated additional malignancy within 5 years before the study entry with the exception of: curatively treated basal cell carcinoma of the skin, curatively treated squamous cell carcinoma of the skin, curatively treated prostate cancer, curatively resected in situ cervical cancer, and curatively resected in situ breast cancer.
• Subjects with a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subjects' participation for the full duration of the trial, or is not in the best interest of the subject to participate, according to the opinion of the treating investigator.
• Significant neurologic or known psychiatric or substance abuse disorders that would interfere with cooperation and the requirements of the trial.
• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (≤6 months prior to enrollment), myocardial infarction (≤6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
• Prior organ transplantation including allogenic stem-cell transplantation.
• Active uncontrolled infection requiring systemic therapy (i.e. I.V. antibiotics).
• Known history of testing positive for HIV or known acquired immunodeficiency syndrome.
• Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening tests positive).

Sponsors & Collaborators

• Gruppo Oncologico del Nord-Ovest: lead
• Merck Serono S.P.A., Italy: collaborator
• Clinical Research Technology S.r.l.: collaborator

Study Sites (8)

Ospedale Oncologico "A. Businco" ARNAS BROTSU

Cagliari, CAGLIARI, 09121, Italy

NOT YET RECRUITING

Azienda Ospedaliero-Universitaria Policlinico "G. Rodolico-S. Marco

Catania, CATANIA, 95123, Italy

NOT YET RECRUITING

Azienda Ospedaliero-Universitaria Careggi

Florence, FIRENZE, 50134, Italy

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori (INT) di Milano

Milan, Milano, 20133, Italy

RECRUITING

Irccs Humanitas Research Hospital

Rozzano, Milano, 20089, Italy

NOT YET RECRUITING

Irccs Fondazione G. Pascale

Napoli, Napoli, 80131, Italy

RECRUITING

AOU Luigi Vanvitelli

Napoli, NAPOLI, 80138, Italy

NOT YET RECRUITING

Azienda Ospedaliero-Universitaria Sant'Andrea

Roma, roma, 00189, Italy

NOT YET RECRUITING

MeSH Terms

Conditions

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

Interventions

Cetuximab; avelumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2025
• First Posted: March 11, 2025
• Study Start: February 20, 2025
• Primary Completion (Estimated): August 20, 2027
• Study Completion (Estimated): February 20, 2028
• Last Updated: March 14, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (8)