Combining Cetuximab and Dalpicilib for HPV Negative Head and Neck Cancer

Cetuximab Plus Dalpicilib in the Second-line Treatment of Patients With HPV Negative, PD-1 Resistant Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma: an Open-label,Single Arm,Phase 2 Trial

This study is testing a new combination of two drugs, cetuximab and dalpicilib, to see if it can help people with HPV-negative head and neck cancer that hasn't responded to other treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 26 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University (Academic / other)
• Drugs / interventions: cetuximab, immunotherapy, pembrolizumab, pablizumab, afatinib, chemotherapy, methotrexate
• Locations: 1 site (Shanghai, Shanghai)
• Trial ID: NCT05721443 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the combination of cetuximab and dalpicilib in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who have shown resistance to PD-1 immunotherapy. The study aims to explore new treatment options for HPV-negative HNSCC, which typically has a poor prognosis and limited response to existing therapies. Participants must have measurable lesions and provide tumor tissue for analysis, ensuring a targeted approach to treatment. The trial is designed to assess the efficacy and safety of this novel combination therapy.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18-75 with recurrent or metastatic HPV-negative HNSCC who have previously received PD-1 immunotherapy.

Not a fit: Patients with HPV-positive head and neck cancer or those who have not previously undergone PD-1 immunotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with HPV-negative, PD-1 resistant head and neck cancer, potentially improving survival and quality of life.

How similar studies have performed: While this specific combination has not been extensively tested, similar approaches targeting the EGFR signaling pathway in head and neck cancers have shown promise in other studies.

Eligibility criteria

Inclusion Criteria:

* Age 18-75 years, both sexes.
* Patients with histologically confirmed post-surgical recurrent/metastatic or locally advanced inoperable surgically resectable squamous cell carcinoma of the head and neck with measurable lesions (spiral CT scan ≥ 10 mm, meeting RECIST 1.1 criteria).
* Have received at least 1 cycle of prior PD-1 immunotherapy with imaging confirmation of progression or clinician determination of no continued benefit from treatment; provided that this is completed at least 4 weeks prior to the first dose of study drug and all associated toxic events have returned to normal or grade I or less as defined by CTCAE 4.03 classification.
* HPV viral testing determined to be negative, using the IHC method.
* Availability of tumor tissue (paraffin specimens less than 2 years old or fresh tumor tissue) for detection of PD-L1 and CDK4-related genes.
* ECOG score of 0 or 1.
* Expected survival of ≥ 12 weeks.
* Normal major organ function within 2 weeks prior to treatment, i.e., meeting the following criteria：Bone marrow function: hemoglobin ≥ 100 g/L without transfusion or colony-stimulating factor support therapy, white blood cell count ≥ 4.0\*10\^9/L or neutrophil count ≥ 2.0\*10\^9/L, and platelet count ≥ 100\*10\^9/L; Liver: serum total bilirubin level ≤ 1.5 times the upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 times the upper limit of normal; Renal: blood creatinine level below 1.5 times the upper limit of normal or creatinine clearance ≥ 60 ml/min and urea nitrogen ≤ 200 mg/L; Urine protein \<+, or if urine protein + then total 24-hour protein must be \<500mg; Blood glucose: within normal range and/or with diabetes in treatment but under stable glycemic control; Pulmonary function: baseline FEV1 of at least 2L; if baseline FEV1 \<2L then FEV1 \>800ml expected post-surgery as assessed by a surgical specialist; Cardiac function: no myocardial infarction within 1 year; no unstable angina; no symptomatic severe arrhythmias; no cardiac insufficiency.

Exclusion Criteria:

* Patients previously treated with cetuximab or other anti-EGFR monoclonal antibodies or small molecule tyrosine kinase inhibitors.
* Patients who are currently receiving antineoplastic therapy.
* Patients who have participated or are participating in a clinical trial of another drug/therapy within 4 weeks prior to the first dose of the study drug.
* Patients who have received hematopoietic stimulating factors, such as granulocyte colony-stimulating factor (G-CSF), erythropoietin, etc., within 1 week prior to the first dose of the study drug.
* Positive HIV antibody or syphilis spirochete antibody test results.
* Patients with active hepatitis B or C: If positive for HBsAg or HBcAb, additional HBV DNA testing (results above the upper limit of the normal range). If HCV antibody test result is positive, add HCV RNA test (result above the upper limit of the normal range).
* Known hypersensitivity to recombinant humanized EGFR monoclonal antibody drugs and their components.
* Massive pleural or ascites fluid with clinical symptoms and requiring symptomatic management.
* Active lung disease (interstitial pneumonia, pneumonia, obstructive lung disease, asthma) or a history of active tuberculosis.
* Has any uncontrollable clinical problem, including but not limited to: Persistent or active (severe) infection; Poorly controlled diabetes mellitus; Cardiac disease (Class III/IV congestive heart failure or heart block as defined by the New York Heart Association); Deep vein thrombosis or pulmonary embolism; myocardial infarction; severe or unstable arrhythmia or angina; percutaneous coronary intervention, acute coronary syndrome, coronary artery bypass grafting; cerebrovascular accident, transient ischemic attack, cerebral embolism within 6 months prior to first dose.
* Previous stem cell transplantation or organ transplantation.
* Those with a history of psychotropic substance abuse and unable to abstain or a history of psychiatric disorders.
* Other serious, acute or chronic medical conditions or abnormalities in laboratory tests that, in the judgment of the investigator, may increase the risk associated with study participation or may interfere with the interpretation of study results.
* Patients who, in the judgment of the investigator, have poor compliance or other conditions that make them unsuitable for participation in this trial.
* Patients with a history of other malignancies within five years.

Where this trial is running

Shanghai, Shanghai

• the Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine — Shanghai, Shanghai, China (Recruiting)

Study contacts

• Principal investigator: Yue He, M.D. — the Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
• Study coordinator: Guoxin Ren, M.D.

Conditions Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma