Cetuximab Plus Dalpicilib in Patients With HPV Negative, PD-1 Resistant R/M HNSCC

NCT05721443 | Unknown Phase 2 DMC

• 1 other identifier: SH9H-2022-T252-1
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This study is the first clinical study in PD-1 resistant patients with head and neck squamous cell carcinoma with drugs targeting EGFR signaling pathway combined with CDK4/6 inhibitors, which explores the new combination therapies urgently needed in clinical practice and lays a foundation for subsequent studies, with important scientific research significance and clinical value.

Conditions

Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• objective response rate

  ORR was defined as the percentage of participants in the analysis population who have a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1.

  24 months

Secondary Outcomes (4)

• overall survival

  24 months

• Progression Free Survival Per RECIST 1.1

  24 months

• Number of Participants Experiencing an Adverse Event (AE).

  24 months

• Quality of life#EORTC QLQ-C30 scale#

  24 months

Study Arms (1)

Dalpiciclib+cetuximab

EXPERIMENTAL

The dosing regimen for cetuximab combined with dalpiciclib is: the starting dose of cetuximab is 400 mg/m2, titrated over 120 minutes, and the titration rate should be limited to 5 ml/min. A maintenance dose of 250 mg/m2, titrated over not less than 60 minutes, with pretreatment with H1 receptor blocker desensitization prior to dosing, administered once weekly. The recommended dose of dalpiciclib is 150 mg once daily for 21 days, followed by 7 days of discontinuation (3/1 dosing regimen) for a 28-day treatment cycle. Take the drug at approximately the same time each day. If the patient vomits or misses a dose, the dose should not be made up that day. The next dose should be taken as usual. Subjects will continue treatment with cetuximab in combination with dalpiciclib until termination criteria are met.

Drug: Dalpiciclib+cetuximab

Interventions

Dalpiciclib+cetuximab DRUG

The dosing regimen for cetuximab combined with dalpiciclib is: the starting dose of cetuximab is 400 mg/m2, titrated over 120 minutes, and the titration rate should be limited to 5 ml/min. A maintenance dose of 250 mg/m2, titrated over not less than 60 minutes, with pretreatment with H1 receptor blocker desensitization prior to dosing, administered once weekly. The recommended dose of dalpiciclib is 150 mg once daily for 21 days, followed by 7 days of discontinuation (3/1 dosing regimen) for a 28-day treatment cycle. Take the drug at approximately the same time each day. If the patient vomits or misses a dose, the dose should not be made up that day. The next dose should be taken as usual. Subjects will continue treatment with cetuximab in combination with dalpiciclib until termination criteria are met.

Dalpiciclib+cetuximab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University: lead

Study Sites (1)

the Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200011, China

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Condition Hierarchy (Ancestors)

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

Study Officials

• Yue He, M.D.

  the Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guoxin Ren, M.D.

CONTACT

13916948812; renguoxincn@sina.com

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: November 9, 2022
• First Posted: February 10, 2023
• Study Start: April 1, 2023
• Primary Completion: January 1, 2024
• Study Completion: January 1, 2026
• Last Updated: February 10, 2023

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)