Combination treatment of Penpulimab and Cetuximab for advanced head and neck cancer

An Exploratory Clinical Study to Evaluate the Efficacy and Safety of Penpulimab in Combination With Cetuximab as First-line Treatment in Patients With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (R/MSCCHN)

This study is testing a new combination of two medications, Penpulimab and Cetuximab, to see if they can help people with advanced head and neck cancer who haven't had treatment before.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 48 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Eye & ENT Hospital of Fudan University (Academic / other)
• Drugs / interventions: cetuximab, nimotuzumab, gefitinib, afatinib, chemotherapy, immunotherapy, prednisone, Penpulimab
• Locations: 2 sites (Changchun, Jilin and 1 other locations)
• Trial ID: NCT05260671 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of Penpulimab, a PD-1 antibody, in combination with cetuximab as a first-line treatment for patients with recurrent or metastatic squamous cell carcinoma of the head and neck. The study is a multicenter, prospective, single-arm exploratory trial aiming to enroll 48 patients who have not received prior treatment for their condition. Participants will receive Penpulimab and cetuximab intravenously, with treatment cycles lasting 14 days. The trial will assess the response to this combination therapy based on measurable tumor lesions and safety profiles.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed recurrent or metastatic squamous cell carcinoma of the head and neck that is not suitable for local treatment.

Not a fit: Patients with localized disease that can be treated with surgery or radiotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with advanced head and neck cancer.

How similar studies have performed: Previous studies have shown promising results with PD-1 and cetuximab combination therapies, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* Age: ≥ 18 years, male or female;
* Histologically confirmed squamous cell carcinoma of the head and neck (oral cavity, oropharynx, larynx, hypopharynx) (SCCHN);
* Recurrent/metastatic SCCHN not suitable for local treatment such as surgery or radiotherapy in the opinion of the investigator;
* At least one measurable tumor lesion according to RECIST 1.1 criteria;
* The tumor expresses PD-L1, with a comprehensive positive score CPS ≥ 1;
* Eastern Cooperative Oncology Group (ECOG) PS: 0-1
* Expected survival ≥ 3 months;
* Normal function of major organs, meeting the following criteria: blood routine examination criteria must be met: (no blood transfusion within 14 days before screening) 1) HB ≥ 90 g/L; 2) ANC ≥ 1.5 × 109/L; 3) PLT ≥ 75 × 109/L; biochemistry: (without transfusion or blood product within 14 days before screening) 1) BIL ≤ 1.5 × upper limit of normal (ULN) (≤ 3 × ULN for patients with Gilbert's syndrome); 2) ALT and AST ≤ 2.5 × ULN (≤ 5 × ULN for patients with liver metastasis); 3) Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50ml/min (Cockcroft-Gault formula); 4) Coagulation function: activated partial thromboplastin time (APTT), international normalized ratio (INR), prothrombin time (PT) ≤ 1.5 × ULN; left ventricular ejection fraction (LVEF) ≥ 50% assessed by cardiac Doppler ultrasound;
* Women of childbearing potential must have a negative pregnancy test (serum or urine) within 14 days prior to enrollment and are willing to use reliable contraception during the trial and must be non-lactating patients; male subjects must use reliable contraception from the start of treatment to 6 months after the last dose;
* The subjects voluntarily join the study, sign the ICF, have good compliance, and cooperate in the follow-up

Exclusion Criteria:

* Received systemic chemotherapy, but excluding chemotherapy for locally advanced disease as a part of multimodal treatment. Note: Chemotherapy for locally advanced disease includes induction chemotherapy, radiotherapy with concurrent chemotherapy, and adjuvant chemotherapy;
* Previous immunotherapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibodies or any other antibody or drug specifically targeting T cell costimulation or immune checkpoint pathways;
* Previous use of anti-EGFR drugs such as cetuximab, nimotuzumab, gefitinib, and afatinib;
* Pregnant or lactating, or planning to become pregnant during the study period;
* Current participation and receipt of study treatment, or participation in an investigational drug trial or use of an investigational device within 4 weeks prior to randomization;
* Presence of uncontrolled or symptomatic active central nervous system (CNS) metastases, which may present with clinical symptoms, cerebral edema, spinal cord compression, carcinomatous meningitis, leptomeningeal disease, and/or progressive growth;
* Any active autoimmune disease or history of autoimmune disease (but not limited to autoimmune hepatitis, interstitial pneumonia, enteritis, hypophysitis, vasculitis, nephritis; positive HIV test or history of the above diseases, or history of organ transplantation; but the following patients are allowed: vitiligo, psoriasis, alopecia, well-controlled type I diabetes mellitus, Hypothyroidism with euthyroidism treated by replacement therapy;
* Treatment with systemic immunosuppressive drugs within 2 weeks before the start of study treatment or anticipation of the need for systemic immunosuppressive drugs during study treatment, with the following exceptions: 1) Intranasal, inhaled, topical steroids, or topical steroids (e.g., intra-articular); 2) Physiological doses of systemic corticosteroids (≤ 10 mg/day prednisone or equivalent); 3) Steroid premedication for hypersensitivity (e.g., premedication for CT scan);
* Significant cardiovascular disease, such as cardiac insufficiency above class II (New York Heart Association (NYHA) classification) or left ventricular ejection fraction \< 50%, unstable angina pectoris, myocardial infarction within 1 year, arrhythmia requiring treatment, QTc ≥ 450 ms (male), QTc ≥ 470 ms (female);
* The subject has an active infection or infectious disease, requiring systemic antibacterial, antifungal, or antiviral treatment, including tuberculosis infection; or has an unexplained fever (body temperature \> 38.5℃) during the screening period or prior to the first dose;
* Interstitial lung disease or non-infectious lung disease (including past medical history and prevalence), uncontrolled systemic diseases, including pulmonary fibrosis, acute lung disease, diabetes (fasting blood glucose (FBG) \> 8.9 mmol/L), hypertension (systolic blood pressure ≥ 150 mmHg, diastolic blood pressure ≥ 90 mmHg), kidney disease (urine routine showed urine protein ≥ 2 +, or 24 h urine protein quantification \> 1.0g), etc., except for local interstitial pneumonia induced by radiotherapy;
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage;
* Subjects with a history of other malignancies within the past 5 years, but except for cured cervical carcinoma in situ, squamous cell carcinoma of the skin, basal cell carcinoma of the skin, localized prostate cancer, or other carcinomas in situ with definitive resection;
* Virological screening meets any of the following criteria: hepatitis B HBsAg positive and HBV-DNA ≥ 10\^3 copies/ml; hepatitis C: HCV antibody positive and HCV-RNA positive (results greater than the lower limit of detection of the analytical method);
* Participants may need to be vaccinated during the study or have received a live viral vaccine within 4 weeks prior to enrollment. Seasonal influenza vaccine without live virus is permitted.
* Patients with other concomitant diseases that seriously jeopardize the patient's safety or affect the patient's completion of the study, as judged by the investigator.

Where this trial is running

Changchun, Jilin and 1 other locations

• Department of radiotherapy,The First Bethune Hospital of Jilin University — Changchun, Jilin, China (Recruiting)
• Department of Radiotherapy, Eye & ENT Hospital of Fudan University — Shanghai, China (Recruiting)

Study contacts

• Principal investigator: Xiaoshen Wang — Eye & ENT Hospital of Fudan University
• Study coordinator: Xiaoshen Wang

Conditions Head and Neck Neoplasms; Recurrent Disease; Metastatic Cancer