Trial Title:
A Clinical Study to Evaluate the Safety and Tolerability of JS001sc in Advanced Nasopharyngeal Carcinoma
NCT ID:
NCT05751486
Condition:
Advanced Nasopharyngeal Carcinoma
Conditions: Official terms:
Carcinoma
Nasopharyngeal Carcinoma
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Parallel Assignment
Intervention model description:
Parallel
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Toripalimab injection(subcutaneous)/JS001sc
Description:
JS001sc Q3W combination with gemcitabine and cisplatin.
Arm group label:
JS001sc Q3W
Intervention type:
Biological
Intervention name:
Toripalimab injection(subcutaneous)/JS001sc
Description:
JS001sc long period combination with gemcitabine and cisplatin.
Arm group label:
JS001sc long period
Intervention type:
Biological
Intervention name:
Toripalimab /JS001
Description:
JS001 IV (if applicable) .
Arm group label:
JS001 IV (if applicable)
Intervention type:
Biological
Intervention name:
Toripalimab injection(subcutaneous)/JS001sc
Description:
Additional cohort (if applicable)
Arm group label:
Additional cohort (if applicable)
Summary:
The purpose of this phase I clinical study was to evaluate the safety and tolerability of
JS001sc monotherapy and combination with gemcitabine and cisplatin (GP) in patients with
Advanced nasopharyngeal carcinoma.
Detailed description:
This study is the first human study of Toripalimab injection(subcutaneous) .Patients with
advanced nasopharyngeal carcinoma were planned to be enrolled.
Two cohorts were initially proposed, Toripalimab injection (subcutaneous) Q3W combination
with gemcitabine and cisplatin (GP) regimen and JS001sc long-term dosing combined with GP
regimen.
Cohort 1: JS001sc Q3W SC combined with GP regimen chemotherapy; Cohort 2: JS001sc long
period SC combined with GP regimen chemotherapy; IV cohort (if applicable): the Safety
Monitor Committe (SMC) will discuss whether to conduct an IV cohort and determine the
dose/frequency of the IV cohort, based on the initial safety and clinical pharmacological
data of triprilimab injection in combination with the GP regimen; Additional cohort (if
applicable): the exploration of additional dosing/frequency will be discussed by the SMC
based on prior safety and clinical pharmacological data.
Subjects with no disease progression (PD) after the combination chemotherapy period
(JS001/JS001SC combined with GP regimen, in one therapeutic cycle of three weeks, for at
most 6 cycles) will enter the monotherapy maintenance period.JS001/JS001sc monotherapy
maintenance treatment of the same dose/frequency f the combination chemotherapy
period.Based on the preliminary safety and clinical pharmacological data, SMC will
discusses whether to change the dose/frequency.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. The subjects voluntarily participated in the study with full informed consent and
signed written informed consent form;
2. Recurrent/metastatic nasopharyngeal carcinoma diagnosed histologically and/or
cytologically,Patients with no loco-regional therapy or radical therapy of primary
metastatic （UICC&AJCC 8th edition) or recurrent nasopharyngeal carcinoma after
radical therapy.No previous systematic treatment for recurrent or metastatic
disease.
3. Patients with recurrent nasopharyngeal carcinoma after radical therapy must be
satisfied that the disease recurrence more than 6 months after the last radiotherapy
or chemotherapy.
4. There should be at least one measurable lesion according to RECIST V1.1 evaluation
criteria. The lesions that have previously received radiotherapy should not be
considered as target lesions unless there is definite progression after
radiotherapy.
5. Age of 18-75 years (inclusive), male or female;
6. The physical status score is 0 or 1 on the Eastern Oncology Collaboration (ECOG)
scale;
7. The expected survival is ≥3 months;
8. Major organ functions meet the following requirements.No blood transfusion or blood
products, hematopoietic stimulating factors or other drugs were used to correct
blood cell counts within 14 days prior to the examination：
Neutrophil absolute count ≥1.5 × 109/L;
Platelet count ≥ 100 × 109/L;
Hemoglobin ≥ 90 g/L;
Serum albumin ≥ 30 g/L;
Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN) with biliary obstruction
resolved prior to randomization;
Alkaline phosphatase (ALP)≤ 3 × ULN, ALP≤ 5 × ULN (Patients may have liver or bone
metastasis);
Albumin ≥ 30 g/L;
Serum creatinine (Cr) ≤ 1.5 × ULN, Cr clearance ≥ 60 mL/min (Cockcroft -Gault
Formulas, refer to attachment 2);
International Normalized Ratio (INR), prothrombin time (PT), and activated Partial
thrombin Time (aPTT) ≤ 1.5× ULN (Patients should not have received anticoagulant
therapy);If Patients receiving anticoagulant therapy that they should use a steady
dose;
9. Within 7 days prior to the first dose, women of reproductive age must be confirmed
as having a negative serum pregnancy test and consent to use effective contraception
during the duration of study drug use and for 150 days after the last dose. Women of
childbearing age are defined as sexually mature women: 1) no hysterectomy or
bilateral ovariectomy, 2) Natural menopause did not last for 24 consecutive months
(Amenorrhea after cancer treatment does not rule out fertility);Male patients with a
female partner of reproductive age agreed to use effective contraception during the
study drug use period and for 6 months after the last dose;
Exclusion Criteria:
1. A history of severe allergic reactions to to any component of JS001;
2. A history of hypersensitivity to gemcitabine or cisplatin or any excipients;
3. Prior treatment with Anti-PD-1 antibody, anti-PD-L1 or anti-CTLA-4 antibody;
4. Received antitumor therapy ,Such as, chemotherapy, radiotherapy,immune therapy
therapy, biological drugs therapy or other investigational drugs within 4 weeks or 5
half-lives period （Choose the shorter one）before the administration of the first
dose;Receive traditional Chinese medicine or Chinese patent medicine preparations
with anti-tumor indications within 2 weeks prior to initial administration;
5. Within 28 days prior to the first study drug administration, there are other major
surgeries except for the diagnosis of nasopharynx carcinoma, or assessed by
researchers and specialists that they did not have fully recovered from the
complications of major surgery;
6. The toxic response of previous anti-tumor treatment has not been restored to CTCAE
0-1, except for hair loss and pigmentation.Irreversible toxicity reasonably expected
not to be aggravated by the drug under study (e.g. hearing loss). They can be
included after confirmation with the sponsor.
7. A subject with clinical symptoms of CNS and/or cancer meningitis (such as cerebral
edema, hormone intervention, or brain metastases) No clear surgery and/or
radiotherapy for spinal cord compression, or for spinal cord compression that
previously diagnosed and treated, no evidence indicates that the first study of pre
-dating diseases in clinical stability ≥2 weeks of clinical clinic; Received the
treatment of brain or meningeral membrane, such as clinical stability has been
maintained for at least 2 months, and has stopped systemic hormone therapy (dose> 10
mg/day dawnone or other curative hormones such as);
8. Poorly controlled the thoracic effusion, pericardial effusion, or ascites that need
to be drained (thoracic ascites ≥1 times/month)
9. Poorly controlled tumor-related pain:
For patients who need analgesic treatment, they must receive a stable dose treatment
before participating in the study ; Before entering the group, a clinical indication
lesions should be treated for local treatment (for example, bone metastases or
metastasis of neurotransidal);
10. Featured pulmonary fibrosis, drug -induced pneumonia, mechanized pneumonia (that is,
occlusion fine pineitis), radioactive pneumonia with clinical symptoms or steroids,
active pneumonia or other medium -weight lungs that seriously affect lung function
that seriously affect lung function disease;
11. The first 4 weeks before the medication found that there were necrotic lesions, and
the researchers judged that there was a risk of hemorrhage;
12. Within the first 5 years of administration, there are other malignant tumors other
than nasopharyngeal cancer (except for cured cervical in situ cancer, base or
squamous cell skin cancer, limited prostate cancer or Ductal carcinoma in situ of
breast);
13. The subject has any active autoimmune disease or a history of autoimmune diseases
within two years. Except for the following situations: 1) patients with thyroid
dysfunction, receiving stable dose thyroid hormone replacement treatment; 2)
receiving stable insulin therapy schemes Later, patients with type I diabetes were
obtained; 3) skin diseases that do not need to be treated with whole body, such as
psoriasis, vitiligo, etc. (for more comprehensive list of autoimmune diseases, see
Annex 4);
14. Severe infections (CTCAE> 2) within 28 days before the administration (CTCAE> 2),
such as severe pneumonia, fungal ledis, infection complications, etc. that need to
be hospitalized;
15. Availability with active lung tuberculosis (TB) is undergoing anti -tuberculosis
treatment or screening within one year before receiving anti -tuberculosis
treatment;
16. It suffers from corticosteroids that require long -term use of immunosuppressive
drug treatment, or the use of immunosuppressive dose (dose> 10 mg/day or other
curative hormones such as 10 mg/day);
17. Received any live vaccine within 4 weeks before the medication (for example,
vaccines for infectious diseases, such as influenza vaccines, chickenpox vaccines,
etc.);
18. Women of pregnancy or lactation;
19. Known human immune defect virus (HIV) positive patients;
20. Hepatitis B core antibodies (HBCAB) or hepatitis B surface antigen (HBSAG) positive
detection of HBV DNA copy number ≥1000CPS/ml or reference value limit;
21. Hepatitis C (HCV) antibody positive at the same time detected HCV RNA copies of
positive;
22. Patients who have been transplanted in the same kind of album bone marrow or
previously performed physical organ transplantation;
23. There are severe nerve or mental illness, including dementia and seizures;
24. Due to NCI-CTCAE ≥ 2 peripheral neuropathy;
25. With major cardiovascular diseases, such as the New York Heart Diseases (NYHA) heart
function grading II or above heart disease (see Annex 3), the myocardial infarction
and control within 3 months before the first study; Unstable angina pectoris;
Knitrines of patients with coronary arteries, congestive heart failure of the above
standards, or left ventricular ejection scores <50%of patients must use the
optimized stable medical plan determined by the doctor. If appropriate, you can
consult the heart. Sick expert;
26. Investigators are judged that they are not suitable for other situations in this
study, including but not limited to any disease or medical history that may confuse
the results o study and interfere with patients.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat-sen University Cancer Center
Address:
City:
Guangzhou
Zip:
510060
Country:
China
Status:
Recruiting
Contact:
Last name:
Ruihua Xu, M.D.
Phone:
86 13922206676
Email:
xurh@sysucc.org.cn
Start date:
October 21, 2022
Completion date:
December 30, 2025
Lead sponsor:
Agency:
Shanghai Junshi Bioscience Co., Ltd.
Agency class:
Other
Source:
Shanghai Junshi Bioscience Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05751486
