This study is the first clinical study of first-line treatment of head and neck squamous cell carcinoma with drugs targeting VEGF signaling pathway combined with PD-1 inhibitors in China, 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.
Head and neck cancer is the sixth most common cancer in the world, with more than 550,000 cases and 300,000 deaths worldwide each year. About 75,000 Chinese suffer from head and neck cancer each year, and currently, there are a total of 176,000 patients with head and neck cancer in China. More than 95% of head and neck cancers are squamous cell carcinomas, and head and neck squamous cell carcinoma (SCCHN) disrupts and affects the patient's appearance and basic physiological functions, sensory functions, and language functions, thus affecting the patient's quality of life. Most head and neck squamous cell carcinomas are incurable, and they will develop local recurrence and metastasis. More than 60% of patients with head and neck squamous cell carcinoma have stage III or IV disease characterized by large size tumors with marked local invasion, evidence of metastasis to regional lymph nodes, or both. Locally advanced head and neck cancer has a high risk of local recurrence and distant metastasis and a poor prognosis. Over the past 20 years, multimodal treatment approaches have steadily improved cure rates while striving to maintain patient function and quality of life. Currently, there are a large number of ongoing clinical trials that combine targeted therapies and immunotherapies. The basic rationale behind these combinations is that they combine different immunological and tumor biological mechanisms to enhance antitumor activity; in addition, some evidence suggests that targeted therapies can enhance certain aspects of the "cancer-immune cycle" (e.g., tumor antigenicity, T cell priming/trafficking/infiltration, etc.) to synergistically enhance immunotherapy. This clinical study involved Recombinant Humanized Anti-PD-1 Monoclonal Antibody Injection (Camrelizumab), a Class 1 new therapeutic biological product developed by Jiangsu Hengrui Medicine Co., Ltd., which was approved by NMPA in May 2019 for the treatment of relapsed or refractory classical Hodgkin's lymphoma, by NMPA in March 2020 for the treatment of patients with advanced hepatocellular carcinoma who have received sorafenib and/or oxaliplatin-based systemic chemotherapy, and in June 2020 for the second-line treatment of esophageal squamous cell carcinoma and first-line treatment of non-squamous non-small cell lung cancer. Preclinical study data showed that camrelizumab had comparable in vivo efficacy and safety compared with similar drugs abroad. Since 2015, Hengrui has simultaneously carried out a number of phase I/II clinical trials in Australia and China to preliminarily verify the safety, tolerability and efficacy of camreibizumab in the treatment of advanced solid tumors. This clinical study also involved apatinib mesylate developed by Jiangsu Hengrui Medicine Co., Ltd. and marketed in 2014. Apatinib mesylate is a small molecule targeted drug, a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor, which exerts anti-angiogenic effect mainly by inhibiting VEGFR to treat malignant tumors. Preclinical studies have shown that its anti-tumor effect is superior to that of similar drugs. In 2014, apatinib mesylate has been used in patients with advanced gastric or gastro-esophageal junction adenocarcinoma who have progressed or relapsed after at least 2 prior systemic chemotherapies.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
81
Camrelizumab 200 mg IV on Day 1 of each 3-week cycle for up to 24 months
Cisplatin 75 mg/m\^2 or Carboplatin AUC5 IV on Day 1 of each 3-week cycle (4 to 6 cycle maximum)
Docetaxel 75 mg/m\^2 IV on Day 1 of each 3-week cycle (4 to 6 cycle maximum)
Apatinib 250mg qd for up to 24 months
Carboplatin at a target AUC 5 IV on Day 1 of each 3-week cycle (6 cycle maximum)
the Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai, China
Overall Survival (OS) in All Participants
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up.
Time frame: 12 months
Progression Free Survival Per RECIST 1.1
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Time frame: 12 months
Objective Response Rate Per RECIST 1.1
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.
Time frame: 12 months
Duration of Response Per RECIST 1.1
Duration of response-defined as the time from first documented complete or partial response to radiographically confirmed disease progression or death from any cause, whichever occurred first.
Time frame: 24 months
ORR in Participants With PD-L1 CPS ≥1
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.
Time frame: 12 months
ORR in Participants With PD-L1 CPS ≥20
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.
Time frame: 12 months
DOR in Participants With PD-L1 CPS ≥1
Duration of response-defined as the time from first documented complete or partial response to radiographically confirmed disease progression or death from any cause, whichever occurred first.
Time frame: 24 months
DOR in Participants With PD-L1 CPS ≥20
Duration of response-defined as the time from first documented complete or partial response to radiographically confirmed disease progression or death from any cause, whichever occurred first.
Time frame: 12 months
Number of Participants Experiencing an Adverse Event (AE).
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants that experienced at least one AE was reported for each treatment arm.
Time frame: 12 months
Quality of life(EORTC QLQ-C30 scale)
The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the GHS question "How would you rate your overall health during the past week?" (Item 29) and the QoL question "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent).
Time frame: 12 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.