Combining chemotherapy with cetuximab and avelumab for advanced head and neck cancer

A Single-arm Phase II Study of Cetuximab Plus Platinum and Taxane-based Chemotherapy Followed by AVElumab and Cetuximab as First-line Therapy for Recurrent/Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC) Patients With PD-L1 Combined Positive Score (CPS)≥1≤19: the Immunotherapy Sequenc

This study is testing a new treatment plan that combines chemotherapy with two medications, cetuximab and avelumab, to see if it helps people with advanced head and neck cancer live longer without their disease getting worse.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 67 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Gruppo Oncologico del Nord-Ovest (Academic / other)
• Drugs / interventions: Cetuximab, chemotherapy, immunotherapy, prednisone, avelumab, pembrolizumab
• Locations: 8 sites (Cagliari, CAGLIARI and 7 other locations)
• Trial ID: NCT06869473 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial evaluates the effectiveness of a sequential treatment approach for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who have a PD-L1 combined positive score between 1 and 19. Participants will first receive three cycles of platinum and taxane-based chemotherapy combined with cetuximab, followed by maintenance therapy with avelumab and cetuximab. The primary goal is to improve the six-month progression-free survival rate from 40% to 55%. This innovative strategy aims to leverage the immune-stimulating effects of chemotherapy and anti-EGFR therapy before transitioning to immunotherapy.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with confirmed recurrent or metastatic HNSCC and a PD-L1 CPS between 1 and 19 who have not received prior systemic therapy.

Not a fit: Patients with lower PD-L1 expression scores or those who have previously undergone systemic therapy for their advanced disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival outcomes for patients with advanced head and neck cancer.

How similar studies have performed: While the approach of combining chemotherapy with immunotherapy is being explored in various contexts, this specific sequential strategy is relatively novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. Subjects able to sign the informed consent and ≥18 y-old.
2. Histologically or cytologically confirmed diagnosis of HNSCC.
3. Confirmed R/M HNSCC (i.e. oral cavity, oropharynx, larynx, hypopharynx) not suitable for curative loco-regional therapy.
4. PD-L1 CPS≥1≤19 (assessment allowed either on primary and/or recurrent/metastatic site of disease).
5. Measurable disease according to RECIST Criteria 1.1.6. Subjects should not have had prior systemic therapy administered in the R/M HNSCC setting.

7.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.

8.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.

10.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.

11.Adequate renal function: calculated or analyzed creatinine clearance ≥ 30 mL/min.

12.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).

13.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.

14.Palliative radiotherapy and/or surgery within 4 weeks before the study entry are allowed.

15.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.

Exclusion criteria:

1. Nasopharyngeal, salivary gland, nasal sinus, and non-melanoma skin cancers are not allowed.
2. Life expectancy lower than 3 months according to the judgement of trial investigator is not allowed.
3. Previous chemotherapy, or biological therapy (i.e. Cetuximab), or immunotherapy administered for R/M setting of HNSCC is not allowed.
4. 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.
5. Known allergic/hypersensitivity reaction to investigational products or any component in their formulations.
6. Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
7. 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.
8. 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.
9. 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.
10. Significant neurologic or known psychiatric or substance abuse disorders that would interfere with cooperation and the requirements of the trial.
11. 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.
12. Prior organ transplantation including allogenic stem-cell transplantation.
13. Active uncontrolled infection requiring systemic therapy (i.e. I.V. antibiotics).
14. Known history of testing positive for HIV or known acquired immunodeficiency syndrome.
15. 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).
16. Live vaccination within 30 days of planned start of study treatment (inactivated vaccines are allowed).
17. Pregnancy (absence of pregnancy must be confirmed by negative serum or urine pregnancy test - ß-HCG - for women of childbearing potential) and/or breast-feeding are not allowed. Subjects of childbearing potential willing to use effective contraceptive method \[Pearl Index \< 1; e.g. oral contraceptive (pill), hormone spiral, hormone implant, transdermal patch, a combination of two barrier methods (condom and diaphragm), sterilization, sexual abstinence\] for the entire study duration and 30 days post-dosing.

Where this trial is running

Cagliari, CAGLIARI and 7 other locations

• Ospedale Oncologico "A. Businco" ARNAS BROTSU — Cagliari, Cagliari, Italy (Not_yet_recruiting)
• Azienda Ospedaliero-Universitaria Policlinico "G. Rodolico-S. Marco — Catania, Catania, Italy (Not_yet_recruiting)
• Azienda Ospedaliero-Universitaria Careggi — Florence, Firenze, Italy (Recruiting)
• Fondazione IRCCS Istituto Nazionale dei Tumori (INT) di Milano — Milan, Milano, Italy (Recruiting)
• Irccs Humanitas Research Hospital — Rozzano, Milano, Italy (Not_yet_recruiting)
• Irccs Fondazione G. Pascale — Naples, Napoli, Italy (Recruiting)
• AOU Luigi Vanvitelli — Naples, Napoli, Italy (Not_yet_recruiting)
• Azienda Ospedaliero-Universitaria Sant'Andrea — Roma, roma, Italy (Not_yet_recruiting)

Conditions Head and Neck Squamous Cell Carcinoma; Recurrent Head and Neck Cancer; Metastatic Head and Neck Cancer; Head and Neck Neoplasms; Squamous Cell Carcinoma; Cetuximab; Avelumab; Anti-EGFR Therapy