A Phase II Clinical Trial to Evaluate the Efficacy and Safety of TQB2618 Injection Combined With Penpulimab in Patients With Recurrent/Metastatic Nasopharyngeal Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- TQB2618 Injection, Pempulimab Injection, Cisplatin Injection, Gemcitabine Hydrochloride Injection
- Conditions
- Nasopharyngeal Carcinoma
- Sponsor
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
- Enrollment
- 47
- Locations
- 8
- Primary Endpoint
- Maximum tolerated dose (MTD)
- Status
- Completed
- Last Updated
- 25 days ago
Overview
Brief Summary
This study consists of two parts:
Part 1 encompasses a safety lead - in phase and an expansion phase. In both phases, subjects with advanced nasopharyngeal carcinoma who have previously failed platinum - based chemotherapy and immune checkpoint inhibitors (such as anti - PD - 1 monoclonal antibodies/anti - PD - L1 monoclonal antibodies, etc.) will be enrolled. The treatment regimen is TQB2618 combined with penpulimab. During the safety lead - in phase, it is to explore whether two dosage groups of TQB2618 in combination with penpulimab (1200mg/1500mg) are safe and tolerable. If both dosage groups are tolerable, in the expansion phase, an additional 18 to 24 subjects will be enrolled to receive TQB2618 (1500mg) + penpulimab (200mg). If the high dosage (1500mg) of TQB2618 is not tolerated, all subjects will receive TQB2618 (1200mg) + penpulimab (200mg).
Part 2 also includes a safety lead - in phase and an expansion phase. It enrolls treatment - naïve subjects with advanced nasopharyngeal carcinoma who have not received prior systemic treatment. These subjects will receive TQB2618 + penpulimab + GP chemotherapy, with the dosage of TQB2618 being 1200mg. In the safety lead - in phase, 3 to 6 subjects will be enrolled. If the treatment combination is safe and tolerable, then in the expansion phase, an additional 24 to 27 subjects will be enrolled.
Both parts of the study will be carried out simultaneously
Detailed Description
This study is divided into two parts: The first part includes the safe introduction phase and the expansion phase. All the patients with advanced nasopharyngeal carcinoma who failed to be treated with platinum chemotherapy and immunocheckpoint inhibitors (anti-PD-1 monoclonal antibody/anti-PD-L1 monoclonal antibody, etc.) were enrolled. The treatment scheme is TQB2618 + Penpulimab Injection. During the safe introduction period, we explored whether the two dose groups (1200mg/1500mg) were safe and tolerable when TQB2618 was combined with Penpulimab Injection. If the two dose groups are tolerable, 18\~24 patients in the second phase of the extended study were randomized to receive TQB2618 in two dose groups (1200mg/1500mg)+Penpulimab Injection (200mg) at a ratio of 1:1. If high dose (1500mg) of TQB2618 is not tolerated, all patients will receive TQB2618 (1200mg)+Penpulimab Injection (200mg). The second part is a randomized controlled study design, which is divided into two groups. All the newly treated patients with advanced nasopharyngeal carcinoma who have not received systematic treatment in the past received TQB2618+Penpulimab Injection+GP chemotherapy and paianzulimab+GP chemotherapy respectively. The dose of TQB2618 was 1200mg. The two parts of research are carried out at the same time.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed nasopharyngeal carcinoma, stage IVb as defined by the AJCC TNM staging system for nasopharyngeal carcinoma, 8th edition in 2017 or subjects with recurrent nasopharyngeal carcinoma who were not suitable for local therapy (For neoadjuvant/adjuvant therapy and radical concurrent chemoradiotherapy, if the disease progresses during treatment or within 6 months after the treatment completion, it should be counted as a failure of first-line treatment of the original plan, and if it exceeds 6 months, it cannot be counted as first-line treatment failure. Alterations of treatment regimen due to drug intolerance are not defined as treatment failure).
- •The first part of enrolled patients shall also meet the following requirements:
- •At least received first-line treatment for recurrent/metastatic lesions, and the last anti-tumor treatment before enrollment had evidence of imaging progress in line with RECIST 1.1 standard;
- •At least have received platinum containing chemotherapy and immunocheckpoint inhibitors (anti-PD-1 monoclonal antibody/anti-PD-L1 monoclonal antibody, etc.) in the past and failed treatment, and there is evidence of imaging progress that meets the RECIST 1.1 standard. Platinum containing chemotherapy and immunotherapy can be used during palliative treatment for recurrent/metastatic lesions, or during radical treatment for locally advanced diseases.
- •Immunotherapy for recurrent/metastatic lesions shall not exceed 2 lines (For neoadjuvant/adjuvant therapy and radical concurrent chemoradiotherapy, if the disease progresses during treatment or within 6 months after the treatment completion, it should be counted as a failure of first-line treatment of the original plan, and if it exceeds 6 months, it cannot be counted as first-line treatment. Failure. Alterations of treatment regimen due to drug intolerance do not defined as treatment failure
- •For the latest immunotherapy before enrollment, if it is aimed at recurrence/metastasis, the best efficacy is at least SD (≥ 6 weeks) or confirmed PR or immunotherapy duration ≥ 12 weeks.
- •The second part of the enrolled patients also need to meet the following requirements:
- •Have not received systemic antitumor therapy for recurrent/metastatic nasopharyngeal carcinoma before;
- •No previous treatment with immune checkpoint inhibitors (anti PD-1 monoclonal antibody/anti PD-L1 monoclonal antibody, etc.). Those who have used no more than one immune checkpoint inhibitor (limited to CTLA-4/PD-1/PD-L1 monoclonal antibody, not including bispecific antibody, not including Penpulimab injection) in the stage of locally advanced radical treatment can be included if they meet the following criteria:
- •If used in the induction phase (with or without other drugs), the best effect in the induction phase is at least PR;
Exclusion Criteria
- •Combined diseases and medical history:
- •Other malignant tumors have occurred or are currently suffering from other malignant tumors within 5 years before the first medication, except for fully treated non-melanoma skin cancer, cervical carcinoma in situ and papillary thyroid carcinoma;
- •Unresolved toxicities greater than CTC AE grade 1 due to any prior therapy, excluding alopecia, neurotoxic sequelae associated with prior platinum therapy;
- •Received major surgical treatment, obvious traumatic injury (excluding needle biopsy, endoscopic biopsy, etc.) within 28 days before the first drug;
- •Arterial/venous thrombotic events, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, occurred within 6 months before the first drug;
- •Active pulmonary tuberculosis, history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonia, radiation pneumonitis requiring treatment, or active pneumonia with clinical symptoms;
- •Cancer-related symptoms and treatment:
- •Received NMPA-approved Chinese patent medicines with anti-tumor indications in the drug insert within 2 weeks prior to the first administration;
- •Received surgery, chemotherapy, radiotherapy or other anti-cancer therapy within 3 weeks before the start of study treatment (the washout period is calculated from the end of the last treatment); those who have received local radiotherapy in the past can be enrolled if they meet the following conditions: radiotherapy The end of the study treatment is more than 3 weeks (more than 2 weeks for brain radiotherapy); and the target lesions selected in this study are not in the radiotherapy area; Or the target lesion is located in the radiotherapy area, but the progress has been confirmed.
- •Previous treatment with anti-TIM-3 antibodies;
Arms & Interventions
TQB2618+Pempulimab+Chemotherapy
Induction therapy: TQB2618 injection + Penpulimab injection + Gemcitabine hydrochloride injection + cisplatin injection; Maintenance treatment: TQB2618 injection +Penpulimab injection; 21 days as a treatment cycle.
Intervention: TQB2618 Injection, Pempulimab Injection, Cisplatin Injection, Gemcitabine Hydrochloride Injection
TQB2618+Pempulimab
TQB2618 injection combined with Penpulimab injection, 21 days as a treatment cycle.
Intervention: TQB2618 injection; Penpulimab injection
Outcomes
Primary Outcomes
Maximum tolerated dose (MTD)
Time Frame: Baseline up to 3 weeks
If dose limiting toxicity (DLT) occurs in 2 or more subjects in a given dose group, the dose level in the previous dose group is considered MTD.
Objective Response Rate
Time Frame: Up to 60 weeks
It is generally defined as complete response plus partial response.
Progression-free Survival
Time Frame: Up to 60 weeks
The period between the beginning of treatment and the observation of disease progression or death from any cause in a patient with a tumor disease.
Dose-limiting toxicity (DLT)
Time Frame: Baseline up to 3 weeks
It refers to serious toxic reactions that occur within the first treatment cycle and are considered unacceptable.
Secondary Outcomes
- Serious Adverse Event(Baseline up to 100 weeks)
- Duration Of Response(24 weeks)
- Overall Survival(Baseline up to 100 weeks)
- Disease Control Rate(Baseline up to 96 weeks)
- Adverse Events(Baseline up to 100 weeks)