Nasopharyngeal Carcinoma, Recurrent or Metastatic
Conditions
Keywords
Nasopharyngeal Carcinoma
Brief summary
The study is to evaluate the efficacy of KL-A167 combined with cisplatin and gemcitabine vs placebo combined with cisplatin and gemcitabine in the treatment of recurrent or metastatic nasopharyngeal carcinoma, as measured by progression-free survival (PFS) per the Response Evaluation Criteria in Solid Tumors RECIST Version 1.1
Detailed description
This study is a randomized, double-blind, placebo-controlled and multicenter study. It is expected that patients with recurrent or metastatic nasopharyngeal carcinoma who had not received systematic anti-tumor treatment before are enrolled, and the efficacy and safety of KL-A167 injection combined with cisplatin and gemcitabine are compared with placebo combined with cisplatin and gemcitabine in the treatment of recurrent or metastatic nasopharyngeal carcinoma. Subjects who meet the enrollment requirements will be randomized to the trial group or the control group according to the ratio of 2:1. The stratification factors are: liver metastasis (with vs without) and ECOG score (0 vs 1)
Interventions
DRUGKL-A167
KL-A167 4-6 cycles for combined therapy.KL-A167 maintenance.
DRUGGemcitabine
4-6 cycles for combined therapy
DRUGCisplatin
4-6 cycles for combined therapy.
DRUGPlacebo
4-6 cycles for combined therapy.Placebo maintenance.
Sponsors
Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Intervention model description
multicenter, double-blind, randomized, controlled phase III trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* The ages at the time of signing the informed consent are ≥ 18 years old and ≤ 75 years old, regardless of gender. * Patients with nasopharyngeal carcinoma diagnosed definitively by histology or cytology. * Recurrent or metastatic nasopharyngeal carcinoma:Nasopharyngeal carcinoma patients with distant metastasis at the time of initial diagnosis (stage IVB nasopharyngeal carcinoma as defined by the 8th Edition of the staging system of Union for International Cancer Control and American Cancer Joint Committee); or nasopharyngeal carcinoma patients with local recurrence and/or distant metastasis more than 6 months after the end of previous radical treatment.Have not received systematic treatment for recurrent or metastatic nasopharyngeal carcinoma before; those who have local recurrence are not suitable for local treatment or have been treated locally. * Eastern Cooperative Oncology Group (ECOG) performance status is 0 \~ 1 score, and the expected survival time is ≥ 12 weeks. * At least one measurable lesion according to RECIST 1.1; the lesions that have received radiotherapy are not selected as target lesions. * Patients must provide tissues or tissue specimens for biomarker analysis during the screening period, and the freshly obtained tissues are preferred. Patients who cannot obtain the fresh tissues can provide archived paraffin sections. * Significant organ functions meet the following requirements:a)Blood routine: Neutrophil count (NEUT) ≥ 1.5×109/L; platelet count (PLT)≥100×109/L; hemoglobin ≥ 90 g/L.b)Liver function: Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal value (ULN); total bilirubin (TBIL) ≤ 1.5×ULN; for patients with liver metastasis, ALT and AST ≤ 5×ULN; for patients with liver metastasis or Gilbert syndrome, TBIL ≤ 3×ULN.c)Albumin ≥ 30 g/L.d)Renal function: creatinine clearance rate (CrCl) ≥ 60 ml/min (using standard Cockcroft-Gault formula).e)Coagulation function: International standardized ratio (INR) ≤ 1.5×ULN; activated partial thromboplastin time (APTT) ≤ 1.5×ULN. * Those who have child-bearing potential during the study period and within 6 months after the end of the last dose study (both men and women) must take effective medical contraceptive measures. * Patients voluntarily participate in this study, sign informed consent, and are able to comply with the visits and related procedures specified in the protocol.
Exclusion criteria
* Patients with pathologically diagnosed nasopharyngeal adenocarcinoma or sarcoma. * Central nervous system metastasis is present at the time of screening. * Uncontrollable tumor-related pain. * Other malignant tumors before randomization (except those who have non-melanoma in situ skin cancer, superficial bladder cancer, cervical cancer in situ, breast cancer, localized prostate cancer, etc., which have been cured and not recurred within 3 years, and the investigator considers those who can be enrolled). * It is known that there is a history of allergy to any ingredient of KL-A167 injection or severe hypersensitivity to other monoclonal antibodies, or hypersensitivity to gemcitabine, cisplatin and any excipients. * Have received any of the following treatment:a)Previous immunotherapy, including immune checkpoint inhibitors (such as PD-1 antibody, PD-L1 antibody, CTLA-4 antibody, etc.), immune checkpoint agonists, immune cell therapy and other treatments targeting at the immune mechanism of tumor.b)Any clinical study drugs within 4 weeks before randomization.c)Participation in another clinical study concurrently, unless it is an observational (non-interventional) clinical study or an interventional clinical study follow-up.d)The last dose of non-systemic anticancer therapy (including local radiotherapy, radiofrequency ablation, anti-tumor Chinese patent medicine, etc.) within 2 weeks before randomization.e)Those who were vaccinated with anti-tumor vaccine previously or have been vaccinated with any active vaccine (such as influenza vaccine, varicella vaccine, etc.) within 4 weeks before randomization or plan to do so during the study period.f)Major surgery (except diagnosis of nasopharyngeal carcinoma) or severe trauma was performed within 4 weeks before randomization.g)Any blood components, anemia correcting drugs (including but not limited to drugs which supplement hematopoietic raw materials, raise red blood cells and raise hemoglobin), drugs which raise white blood cells and platelets were used within 2 weeks before randomization. * Concomitant diseases that may affect protocol compliance or trial results, including:a)Major cardiovascular diseases, such as Grade II and above cardiac dysfunction (NYHA standard); myocardial infarction, unstable arrhythmia or unstable angina pectoris within 3 months before randomization; previous history of myocarditis or cardiomyopathy; echocardiography showed ejection fraction \< 50%; QTc interval, male \> 450 msec, female \> 470 msec; ECG examination is abnormal and the investigator considers there is additional risk.b) Symptomatic hypercalcemia (serum calcium\> 2.9 mmol/L ). * The toxicity of previous anti-tumor treatment has not recovered to ≤ CTCAE version 5.0 Level 1 or the level specified in the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | up to 24 month | PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the Independent Review Committee according to RECIST v1.1 or death from any cause, whichever occurs first |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival(PFS) | up to 24 month | Progression-free survival (PFS) assessed by the investigators according to RECIST V 1.1 |
| Objective Response Rate (ORR) | up to 24 month | The percentage of patients with CR and PR assessed by the Independent Review Committee and investigators according to RECIST v 1.1 |
| Disease Control Rate (DCR) | up to 24 month | The proportion of patients who have achieved CR，PR and SD assessed by the Independent Review Committee and investigators according to RECIST v 1.1 |
| Duration of Response (DoR) | up to 24 month | From the date that response criteria are first met to the first occurrence of PD as determined by the Independent Review Committee and investigators according to RECIST v1.1 or death from any cause, whichever occurs first |
| Overall Survival (OS) | up to 24 month | OS, defined as the time from randomization to death or lose of follow, whichever occurs first |
| 1 year and 2 years Overall Survival (OS) rate | up to 24 month | The percentage of patients overall survival in 1 year and 2 years |
| Time to Response（TTR） | up to 24 month | The time from randomization to the date that response criteria are first met assessed by the Independent Review Committee and investigators according to RECIST v 1.1 |
Countries
China
Outcome results
None listed