Overview
This study is a phase II clinical study of Cadonilimab (AK104) combined with chemotherapy in the treatment of PD-1 inhibitor-resistant nasopharyngeal carcinoma.
Description
The purpose is to evaluate the safety and effectiveness of Cadonilimab combined with chemotherapy in the treatment of PD-1 inhibitor-resistant nasopharyngeal carcinoma as the second line and above. This study is a single-arm, phase II clinical study. It is planned to enroll about 30 patients with PD-1 inhibitor resistant nasopharyngeal carcinoma. PD-Ll CPS (<50% vs>50%, subjects whose PD-Ll expression could not be evaluated were classified as<50%) was used as the stratification factor. The study will set up a safety induction period. It is planned to enroll about 6 PD-1 inhibitor resistant subjects first, and the researchers will conduct a preliminary safety assessment. If the safety and tolerability are good, and the preliminary curative effect signal is observed, it will enter the extended group period. When about 15 subjects are selected, effectiveness analysis will be carried out. If 6 of the 15 subjects with severe side effects can not tolerate, the researcher may stop the group of subjects after discussion. In case of poor safety, the researcher decided to revise or stop the study after discussion.
Eligibility
Inclusion Criteria:
- The age at the time of enrollment is more than 18 years old and less than 75 years old, both male and female.
- The Eastern Cancer Cooperation Organization (ECOG) physical fitness score was 0 or 1.
- The expected survival period is more than 3 months.
- Nasopharyngeal carcinoma confirmed by histology or cytology.
- The subject has previously received treatment with PD-1 inhibitor and failed without indication of radical local treatment.
According to the evaluation standard of curative effect of solid tumor, RECIST v l L At
least one measurable lesion.
Exclusion Criteria:
1. Except for nasopharyngeal carcinoma, the subjects had other malignant tumors within 2
years before enrollment. Subjects with other tumors that have been cured by local
treatment, such as basal or cutaneous squamous cell carcinoma, superficial bladder
cancer, cervical or breast cancer in situ, are not excluded.
2. He participated in the treatment of experimental drugs within 4 weeks before the first
study administration.
3. Patients with active autoimmune diseases that require systematic treatment in the past
two years (such as the use of disease improvement drugs, corticosteroids,
immunosuppressive therapy), and replacement therapy (such as thyroxine, insulin, or
physiological corticosteroid replacement therapy for adrenal or pituitary
insufficiency) are not considered as a systemic treatment.
4. Have a history of immune deficiency; HIV antibody test positive; At present, systemic
corticosteroids or other immunosuppressants are being used for a long time.
5. Active tuberculosis (TB) is known. Subjects suspected of active TB should be excluded
from active TB.
6. The history of allogeneic organ transplantation and allogeneic hematopoietic stem cell
transplantation are known.
7. The untreated active hepatitis B subjects (HBsAg positive and HBV-DNA more than 1000
copies/ml (200 IU/ml) or higher than the lower detection limit, whichever is higher)
are required to receive anti hepatitis B virus treatment during the study treatment
period; Active hepatitis C subjects (HCV antibody positive and HCV-RNA level higher
than the lower limit of detection).
8. Major surgical operation or serious injury occurred within 30 days before the first
administration, or major surgical operation planner (determined by the researcher)
within 30 days after the first administration; Minor local operations (excluding
central venous catheterization via peripheral vein puncture) were performed within 3
days before the first administration.
9. There is central nervous system metastasis.
10. There are currently uncontrolled concomitant diseases, including but not limited to
symptomatic congestive heart failure (grade 2 and above determined according to the
functional classification of the New York Heart Association), unstable angina
pectoris, acute myocardial ischemia, poorly controlled arrhythmia, decompensated liver
cirrhosis, nephrotic syndrome, uncontrolled metabolic disorder, severe active peptic
ulcer disease or gastritis, Mental illness/social condition that may limit the
subject's compliance with the research requirements or affect the subject's ability to
provide written informed consent.
11. There was a history of myocarditis, cardiomyopathy and malignant arrhythmia in the
past. Unstable angina pectoris, congestive heart failure or vascular disease (such as
aortic aneurysm or peripheral venous thrombosis requiring surgical repair) that needs
hospitalization within 12 months before the first administration of the drug, or other
cardiac damage that may affect the safety evaluation of the study drug (such as poorly
controlled arrhythmia, myocardial infarction or ischemia); There is a history of
esophageal and gastric varices, serious ulcer, wound healing, gastrointestinal
perforation, abdominal pain, gastrointestinal obstruction, abdominal abscess or acute
gastrointestinal bleeding within 6 months before the first administration; Any
arterial thromboembolic event occurred within 6 months before the first
administration, including venous thromboembolic generation of NC I CTCAE 5.0 grade 3
and above, transient ischemic attack, cerebrovascular accident, hypertensive crisis or
hypertensive encephalopathy; Acute exacerbation of chronic obstructive pulmonary
disease occurred within 1 month before the first administration; There is currently
hypertension and after treatment with oral antihypertensive drugs, the systolic blood
pressure is more than 160 mmHg or the diastolic blood pressure is less than 100 mmHg.
12. Have a history of severe bleeding tendency or coagulation dysfunction; One month
before the first administration, there were blood symptoms with significant clinical
significance, including but not limited to gastrointestinal bleeding, hemoptysis,
screening imaging showed that the tumor wrapped around important blood vessels or had
obvious necrosis and cavity, and the researcher believed that participating in the
study might cause bleeding risk;
13. The toxicity of previous anti-tumor treatment has not been relieved, which is defined
as that the toxicity has not returned to the level 0 or 1 of NC l CTCAE 5.0, or the
level specified in the inclusion/exclusion criteria, except for the sequelae of hair
loss and previous lead treatment related neurotoxicity. Subjects (such as hearing
loss) who have irreversible toxicity and are not expected to worsen after
administration of the study drug may be included in the study after consultation with
the medical examiner. Subjects with long-term toxicity caused by radiotherapy that
cannot be recovered according to the judgment of the researcher may be included in the
study after consultation with the medical supervisor.
14. The live vaccine was vaccinated within 30 days before the first administration, or was
planned to be vaccinated during the study period.
15. Known allergy to any component of any study drug; A history of severe hypersensitivity
to other monoclonal antibodies is known.
16. Known history of mental illness, drug abuse, alcohol or drug abuse.
17. Pregnant or lactating women.
18. Any previous or current disease, treatment, or laboratory test abnormality may confuse
the results of the study, affect the full participation of the subject in the study,
or participation in the study may not be in the best interests of the subject.
19. Local or systemic diseases caused by non-malignant tumors, or diseases or symptoms
secondary to tumors, which can lead to higher medical risk and/or uncertainty of
survival evaluation, such as tumor-like leukemia reaction (white blood cell count>20 X
109/L or cachexia performance (such as known weight loss of more than 10% in the 3
months before screening), etc