Neoadjuvant Camrelizumab With Dalpiciclib for Resectable Head and Neck Squamous Cell Carcinomas

July 20, 2024 updated by: Xingchen Peng, West China Hospital

The Safety and Feasibility of Neoadjuvant Camrelizumab With Dalpiciclib for the Treatment of Resectable Head and Neck Squamous Cell Carcinoma：A Phase 1 Trial

The purpose of this study is to explore the safety and feasibility of anti-programmed cell death protein 1(PD-1) immunotherapy, Camrelizumab, combined with cyclin-dependent kinase 4/6 blockade, Dalpiciclib, as a new neoadjuvant treatment regimen for patients with resectable head and neck squamous cell carcinoma(HNSCC).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Head and Neck Squamous Cell Carcinoma (HNSCC) is the most common malignancies of the head and neck, accounting for 90% of head and neck cancer. The 5-year survival rate under standard treatment is only 50%. 70%~80% of first diagnosed patients already developed into locally advanced status (stage II-Iva). In recent years, the use of neoadjuvant therapy (NAC) followed by surgery or radiotherapy has been advocated because of its higher probability of local/regional failure and distant metastasis after treatment. TPF (Docetaxel + Cisplatin + Fluorouracil) regimen is considered as the standard regimen of induced chemotherapy for head and neck squamous cell carcinoma (especially in laryngeal cancer), which can significantly reduce the patient's distant metastasis rate and prolong overall survival (OS). However, the therapeutic effect of neoadjuvant therapy on head and neck squamous cell carcinoma has reached a bottleneck. In recent years, PD-1 inhibitors have achieved significant effects in the field of tumor therapy and have been approved for the treatment of various tumors including recurrent metastatic head and neck tumors. There are also several prospective clinical research attempting to combine ICB with targeted therapeutic drugs for neoadjuvant therapy of HNSCC. The efficacy and safety results show potential synergy between these drugs.

Recent preclinical studies have shown that CDK4/6 inhibitors promote efficacy of PD-1/PD-L1 inhibitors through tumor antigen presentation enhancing, suppressed proliferation of regulatory T (Treg) cells, effector T- cell activation enhancing, and induction of T- cell memory. The previous study confirmed that CDK4/6 inhibitor combined with ICB can be administered safely in patients with recurrent or metastatic head and neck squamous cell carcinoma(HNSCC) and non-small cell lung carcinoma(NSCC).

In summary, the investigators designed this study to explore the safety and efficacy of anti-PD1 immunotherapy, Camrelizumab, combined with CDK4/6 inhibitor, dalpiciclib, as a new neoadjuvant treatment regimen for patients with resectable HNSCC. It will also provide new ideas, strategies, and experimental evidence for the development of immunotherapy.

Study Type

Interventional

Enrollment (Estimated)

6

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Sichuan
      • Chengdu, Sichuan, China, 610041

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 18 years or above.

  • Patients with pathologically confirmed HNSCC (except for nasopharyngeal carcinoma) and meet the following conditions:

    • were newly diagnosed and without distant metastasis;
    • were deemed surgically resectable evaluated by a head and neck surgeon;
    • were willing to undergo surgery.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
  • Adequate organ and bone marrow function: absolute neutrophil count ≥ 1.5 × 10^9/L, hemoglobin ≥ 80 g/L, platelets ≥ 80 × 10^9/L;ALT, AST and ALP < 2.5× upper limit of normal (ULN), total bilirubin ≤ 2×ULN;albumin≥ 2.8 g/dL；creatinine clearance ≥ 60 ml/min；INR≤ 1.5；APTT≤ 1.5×ULN
  • Written informed consent.

Exclusion Criteria:

  • History of other malignancies (except for the history of malignant tumors that have been cured and have not recurred within 5 years, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, in situ cervical cancer, and gastrointestinal mucosal cancer, etc.）
  • Have an active autoimmune disease requiring systemic treatment or a documented history of clinically severe autoimmune disease.
  • Any history of allergic disease, or a sever hypersensitivity reaction to drugs, or allergy to the study drug components.
  • Any of prior therapy with:anti-PD-1, anti-PD-L1/2, anti-CTLA-4 antibody, anti-EGFR antibody or EGFR-TKIs； antitumor vaccine; any active vaccine against an infectious disease within 4 weeks prior to the first dose or planned during the study period; major surgery or serious trauma within 4 weeks before the first dose; toxicity from prior antitumor therapy has not recovered to ≤ CTCAE Version 5.0 ·Grade 1 or the level specified by the inclusion/exclusion criteria.
  • With serious medical diseases, such as grade II and above cardiac dysfunction (NYHA criteria), ischemic heart disease, supraventricular or ventricular arrhythmia, poorly controlled diabetes mellitus, poorly controlled hypertension, echocardiographic ejection fraction < 50%, etc.
  • With interstitial pneumonitis, non-infectious pneumonitis, active pulmonary tuberculosis, or history of pulmonary tuberculosis infection that were not controlled by treatment.
  • With hyperthyroidism, or organic thyroid disease.
  • With active infection, or unexplained fever during the screening period or 48 hours before the first dose.
  • With active hepatitis B or C, or known history of positive HIV test, or acquired immunodeficiency syndrome.
  • History of a clear neurological or psychiatric disorder.
  • History of drug abuse or alcohol abuse.
  • Women who are pregnant or breastfeeding, or have a reproductive plan from the screening period to 3 months after the end of the study, or have sex without contraceptive measures, or are unwilling to take appropriate contraceptive measures.
  • Received any investigational drug within 4 weeks prior to the first dose, or concurrently enrolled in another clinical trial.
  • Any other factors that are not suitable for inclusion in this study judged by investigators.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Camrelizumab+Dalpiciclib(100mg) 3 patients

Camrelizumab will be given at at a dose of 200 mg intravenously every three weeks on day 1 of a planned 21-day cycle, and two doses before surgery

Dalpiciclib will be given at a dose of 100 mg every day orally with three weeks on and one week off. Four weeks is a cycle and it will be given for two cycles.

For dalpiciclib, there is 2 dose levels, 100mg qd and 150 mg qd, and if no patients experience DLT on 100mg level, 150mg level will be administered.
Drug: Camrelizumab
Camrelizumab will be given at at a dose of 200 mg intravenously every three weeks on day 1 of a planned 21-day cycle, and two doses before surgery
Drug: Dalpiciclib 100mg
Dalpiciclib will be given at a dose of 100 mg every day orally with three weeks on and one week off. Four weeks is a cycle and it will be given for two cycles.
Experimental: Camrelizumab+Dalpiciclib(150mg) 3 patients

Camrelizumab will be given at at a dose of 200 mg intravenously every three weeks on day 1 of a planned 21-day cycle, and two doses before surgery

Dalpiciclib will be given at a dose of 150 mg every day orally with three weeks on and one week off. Four weeks is a cycle and it will be given for two cycles.

For dalpiciclib, there is 2 dose levels, 100mg qd and 150 mg qd, and if no patients experience DLT on 100mg level, 150mg level will be administered.
Drug: Camrelizumab
Camrelizumab will be given at at a dose of 200 mg intravenously every three weeks on day 1 of a planned 21-day cycle, and two doses before surgery
Drug: Dalpiciclib 150mg
Dalpiciclib will be given at a dose of 150 mg every day orally with three weeks on and one week off. Four weeks is a cycle and it will be given for two cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety of combination camrelizumab and dalpiciclib as assessed by number of participants who experience adverse events
Time Frame: Through the study completion, an average of 12 weeks
Number of participants who experience grade 1 or higher adverse events, as defined by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).
Through the study completion, an average of 12 weeks
Feasibility of combination camrelizumab and dalpiciclib as assessed by number of participants who experience adverse events
Time Frame: Through the study completion, an average of 12 weeks
Number of participants who experience grade 1 or higher adverse events, as defined by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).
Through the study completion, an average of 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Major Pathologic Response
Time Frame: Time of surgery
Major Pathologic Response (MPR) was defined as fewer than 10% viable tumor cells.
Time of surgery
Maximum Tolerated Dose (MTD) as determined by number of participants with dose limiting toxicities (DLT)
Time Frame: Through the study completion, an average of 12 weeks
Maximum tolerated dose will be determined by the maximum dose at which the least number of participants experience dose-limiting toxicity. The dose limiting toxicity is defined using the Common Terminology Criteria for Adverse Events (CTCAE).
Through the study completion, an average of 12 weeks
Objective response rate (ORR)
Time Frame: Through the study completion, an average of 12 weeks
Proportion of participants with measurable disease at baseline and have been re-evaluated after at least 1 cycle of therapy with observed reduction in tumor burden as defined by RECIST and iRECIST criteria after 2 doses of Proportion of participants with measurable disease at baseline and have been re-evaluated after at least 1 cycle of therapy with observed reduction in tumor burden as defined by RECIST and iRECIST criteria after 2 doses of nivolumab and ipilimumab.
Through the study completion, an average of 12 weeks
Progression free survival(PFS)
Time Frame: Up to 2 years
Proportion of participants who achieve progression free survival post treatment
Up to 2 years
Overall survival (OS)
Time Frame: Up to 2 years
Proportion of participants who achieve survival post treatment
Up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

West China Hospital

Investigators

  • Principal Investigator: Jin Zhou, MD.,PhD., West China Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 31, 2023

Primary Completion (Estimated)

October 31, 2024

Study Completion (Estimated)

October 31, 2025

Study Registration Dates

First Submitted

October 25, 2023

First Submitted That Met QC Criteria

October 25, 2023

First Posted (Actual)

October 31, 2023

Study Record Updates

Last Update Posted (Actual)

July 23, 2024

Last Update Submitted That Met QC Criteria

July 20, 2024

Last Verified

July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023-1551

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Head and Neck Squamous Cell Carcinoma

Clinical Trials on Camrelizumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Cameroon

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe