Neoadjuvant Adebrelimab Plus Dalpiciclib in Head and Neck Squamous Cell Carcinoma

Neoadjuvant Adebrelimab Plus Dalpiciclib in HPV-negative Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase II Clinical Trial

This study is a single arm phase II trial including 30 patients with III-IVB (according to the 8th edition of UICC/AJCC staging) locally advanced head and neck squamous cell carcinoma (HNSCC) eligible for resection, who receive Adebrelimab plus Dalpiciclib as neoadjuvant regimen before surgery.

This proposed study will evaluate the efficacy and safety of preoperative administration of Adebrelimab plus Dalpiciclib in HNSCC who are eligible for resection.

Study Overview

• Status: Not yet recruiting
• Conditions: Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Adebrelimab and dalpiciclib

Detailed Description

In this study, eligible patients will be enrolled into study arm to accept study treatment. Pathological response rate and objective response rate will be the primary outcome measures. Adverse events will also be recorded.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Pathologically diagnosed with HPV-negative head and neck squamous cell carcinoma (HNSCC), including oral, laryngeal, hypopharyngeal, and HPV-negative oropharyngeal carcinoma (with HPV testing methods for oropharyngeal carcinoma, including p16 immunohistochemistry or HPV DNA tests).
2. Patients with resectable locally advanced head and neck squamous cell carcinoma (LA-HNSCC), classified as stage III-IVB according to the 8th edition of UICC/AJCC staging.
3. Age greater than or equal to 18 and less than 75 at the time of study entry.
4. Karnofsky Performance Status (KPS) score ≥ 70 points.
5. No prior exposure to other relevant anti-tumor treatments.
6. No distant metastasis (DM).
7. Intention to undergo curative treatment.
8. Adequate bone marrow function: total white blood cell count ≥ 3.5 × 10^9 /L, absolute lymphocyte count ≥ 0.8 × 10^9/L, absolute neutrophil count ≥ 1.5 × 10^9/L, platelets ≥ 100 × 10^9 /L, hemoglobin ≥ 90g/L.
9. Adequate hepatic function: bilirubin ≤ 1.5 x ULN; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN.
10. Adequate renal function: serum creatinine ≤ 1.5 x ULN, creatinine clearance (Ccr) ≥ 60 ml/min (if using the Cockcroft-Gault formula), urinalysis indicating urinary protein less than 2+, or 24-hour urinary protein quantification < 1g.
11. Adequate coagulation function: international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN. If the subject is currently receiving anticoagulant therapy, PT within the therapeutic range of the anticoagulant can be accepted.
12. No severe organic heart disease and arrhythmia.
13. Women of childbearing age (15-49 years) must have a negative pregnancy test within 7 days before treatment. Both men and women of reproductive age must use highly effective contraception during the study and for 3 months after treatment.
14. Willingness and ability to sign an approved Informed Consent Form.

Exclusion Criteria:

1. Previous treatment of any other form of anti-tumor therapy;
2. Patients with allergies and congenital immunodeficiency;
3. active infection;
4. Previous organ transplantation;
5. History of autoimmune diseases or other conditions requiring prolonged systemic use of corticosteroids or immunosuppressive therapy;
6. Patients with a history of use of the following drugs (CYP3A4 inhibitors: clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir, ritonavir, nefazodone, nelfinavir, posaconazole, saquinavir, telaprevir, telithromycin, voriconazole and grape sleeve or grape sleeve juice, ziprasidone, lorlostazol, ticagrelor, aprepitant, netupitant, ondansetron, domperidone, etc.; CYP3A4 inducers: rifampicin, carbamazepine, enzalutamide, phenytoin, rifampicin and St. John's wort, efaviren, bosentan, modafinil, etc.);
7. Human Immunodeficiency Virus (HIV) positive;
8. Active hepatitis B or C infection (HBV DNA, HCV RNA exceeding normal upper limits);
9. Abnormal blood counts: White blood cells <3.5×10^9/L, absolute lymphocyte count <0.8×10^9/L, neutrophils <1.5×10^9/L, platelets <100×10^9/L, hemoglobin <90g/L; elevated bilirubin >1.5 times the upper limit of normal, transaminases (AST, ALT) >3 times the upper limit of normal (5 times if liver metastasis), serum creatinine >1.5 times the upper limit of normal; abnormal coagulation function, international normalized ratio (INR) or prothrombin time (PT) >1.5 times the upper limit of normal.
10. Severe cardiovascular, respiratory, or immune system diseases, including urinary obstruction, positive cardiac stress test, myocardial infarction, arrhythmias, obstructive or restrictive lung disease, or other diseases that investigators believe may increase the risk of subjects.
11. Pregnant or lactating females;
12. Patients unwilling to use effective contraception during the treatment period and the following 3 months.
13. Simultaneous participation in other clinical studies.
14. Patients in critical condition unable to complete the investigation.
15. Patients with a history of mental illness (e.g., schizophrenia, bipolar disorder, anxiety disorders, depression, phobias, etc.) or those diagnosed with a mental disorder at the time of clinical trial enrollment or their spouses.
16. Patients or spouses experiencing communication barriers or inability to respond normally due to reasons such as confusion, aphasia, intellectual disability, etc.
17. Presence of other malignant tumor diseases.
18. Other factors deemed unsuitable or likely to affect the subject's participation or completion of the study by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment group; Patients with resectable locally advanced head and neck squamous carcinoma cell carcinoma receive adebrelimab plus dalpiciclib before surgery.

Drug: Adebrelimab and dalpiciclib; Before surgery, the eligible patients received 3 cycles of adebrelimab (1200 mg intravenously every 3 weeks, Day 1, 22 and 43) and 2 cycles of dalpiciclib (150 mg, po, every 4 weeks, day 1-21 and 29-49). Administration dose adjustments were permitted according to the haematological or non-haematological toxicity.; Other Names: Dalpiclib hydroxyethanesulfonate tablets; Adebrelimab iniection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological response rate	The pathological response was evaluated by pTR (the appearance of tumor necrotic cells and keratin fragments with giant cell/tissue cell responses), including significant pathological response (Major pathological response, MPR, pTR-2 ≥ 50%), partial pathological response (Partial pathological response, PPR, pTR-1 10% -49%), and no pathological response (Non pathological response, NPR, pTR-0<10%).	1-year

Collaborators and Investigators

• Sponsor: Zhongzheng Xiang

Study record dates

Study Major Dates

• Study Start (Estimated): January 31, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: December 1, 2023
• First Submitted That Met QC Criteria: December 28, 2023
• First Posted (Actual): January 10, 2024

Study Record Updates

• Last Update Posted (Actual): January 22, 2024
• Last Update Submitted That Met QC Criteria: January 19, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Immunotherapy; Neoadjuvant therapy; CDK4/6 inhibitor; Locally advanced head and neck squamous cell carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: Neo-AdDa

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No