Trial Title:
Cadonilimab+ Paclitaxel (Albumin-bound) Treat Advanced Gastric Adenocarcinoma With PD-(L)1 Inhibitors Resistance
NCT ID:
NCT06118645
Condition:
Gastric Adenocarcinoma
Conditions: Official terms:
Adenocarcinoma
Paclitaxel
Conditions: Keywords:
cadonilimab
paclitaxel (albumin-bound)
gastric adenocarcinoma
PD-(L)1 inhibitors resistance
esophagogastric junction adenocarcinoma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
This is a single-arm, open, multicenter clinical study to evaluate the efficacy and
safety of cadonilimab in combination with paclitaxel (albumin-bound type) as a
second-line treatment for advanced gastric adenocarcinoma or esophagogastric junction
adenocarcinoma The study included a screening period (no more than 28 days after the
subject signed the informed consent letter to the first dose) treatment period (receiving
the appropriate treatment regimen until the disease progression and toxicity of
intolerable withdrawal of the informed consent letter and death or the end of the study,
whichever occurred first) and follow-up period (including safety follow-up and survival
follow-up).
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
cadonilimab combined +paclitaxel (albumin-bound)
Description:
1. In the safe induction phase6 subjects will receive cadonilimab (10mg/kg, Q3W,
intravenous infusion, up to 2 years) and paclitaxel (albumin-bound type)(125
mg/m2,Days1, 8,Q3w, intravenous infusion, up to 8 cycles).
2. If the safety and tolerability are good, and the initial efficacy signal is
observed, the extended enrollment phase will enter the extended enrollment phase of
drug administration and the safety introduction phase
Arm group label:
cadonilimab combined +paclitaxel (albumin-bound)
Summary:
Cadonilimab combined with paclitaxel (albumin-bound) treat advanced gastric
adenocarcinoma or esophagogastric junction adenocarcinoma with PD-(L)1 inhibitors
resistance
Detailed description:
An open, multicenter, Phase II study of cadonilimab combined with paclitaxel
(albumin-bound) in the treatment of advanced gastric adenocarcinoma or esophagogastric
junction adenocarcinoma that has failed prior treatment with PD-(L)1 inhibitors
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Be able to understand and voluntarily sign a written informed consent, which must be
signed prior to performing the specified study procedure required for the study.
2. Age and gender: ≥18 years old and≤75 years old, both men and women.
3. The Eastern United States Cancer Collaborative (ECOG) physical Fitness score was
0-1.
4. Histologically or cytologically confirmed unresectable or metastatic gastric
adenocarcinoma or esophagogastric junction adenocarcinoma (EGJ defined as the center
of the tumor within 5 cm of the anatomic location of the cardia, as described in the
Siewert classification system).
5. Patients who have progressed or become intolerant after prior treatment with a
regimen containing PD-1/PD-L1 monoclonal antibody had a tumor shrinkage response
assessed as CR, PR, or reduced SD(<0% reduction in total target lesion diameter from
baseline according to RECIST v 1.1) and persisted for 4 months or more after
treatment with PD-1/PD-L1 monoclonal antibody If the disease progresses during
neoadjuvant/adjuvant chemotherapy or radical chemoradiotherapy or within 6 months
after the end of the last treatment, it is considered to have received first-line
treatment
6. Expected survival ≥12 weeks.
7. According to RECIST v1.1, subjects must have at least one measurable lesion. For
subjects who have previously received radiotherapy, a radiation-treated lesion may
be considered a target if there is objective evidence of significant progression
after radiotherapy if there is no other alternative target lesion.
8. Subjects are required to provide the most recent archived (at least 2 years old)
and/or freshly obtained tumor tissue samples and at least 3 unstained FFPE
pathological slides.
9. The functions of important organs must meet the following requirements:
(1) Hematological system: Neutrophil count≥1.5×10^9/L; Platelet count≥100×10^9/L;
Hemoglobin≥90g/L; (2) Liver function： Serum albumin≥28g/L; Total bilirubin (TBI)≤1.5×ULN;
Alanine aminotransferase (ALT)≤3×ULN (or≤5×ULN if liver metastates are present);
Aspartate aminotransferase (AST)≤2.5×ULN (or≤5×ULN if liver metastates are present); (3)
Renal function: Calculated creatinine clearance≥50 mL/min (using the Cockcroft-Gault
formula); Female: CrCl = (140- age in years) × weight in kg × 0.85 72 × serum creatinine
in mg/ dL
Male: CrCl = (140- age in years) × weight in kg × 1.00 72 × serum creatinine in mg/ dL
Urinary protein 2+ or 24 hours (h) urinary protein quantification<1.0g. (4) Coagulation
function: Subjects not receiving anticoagulation therapy: INR or APTT ≤ 1.5×ULN; (5)
Cardiac function: Left ventricular ejection fraction (LVEF)≥ 50 10. Fertile female
subjects must undergo a urine or serum pregnancy test within 3 days prior to the first
dosing (if the urine pregnancy test result is not confirmed negative, serum pregnancy
test is required, based on the blood pregnancy result), and the result is negative if the
fertile female subject is not neutered The subject must be on a highly effective
contraceptive method since screening and must consent to continued use of the
contraceptive method for 120 days after the last dose of the study drug; Whether to stop
contraception after this time point should be discussed with the investigator.
11.If an unsterilized male subject has sex with a fertile female partner, the subject
must use an effective contraceptive method from the beginning of screening until the
120th day after the last dose; Whether to stop contraception after this time point should
be discussed with the investigator.
12.Subjects were willing and able to comply with the schedule for visiting treatment
protocol laboratory tests and other study requirements.
Exclusion Criteria:
Patients with any of the following criteria were excluded from the study
1. Other pathological types confirmed by histopathological or cytological examination,
such as squamous cell carcinoma, undifferentiated carcinoma, neuroendocrine
carcinoma and Mixed pathological types will be judged according to the main
components, adenocarcinoma components confirmed by the pathologist greater than 70%
can be included in the group
2. Participants had other malignancies within 3 years prior to enrollment. Subjects
with other malignancies that have been cured by local treatment, such as basal or
cutaneous squamous cell carcinoma, superficial bladder cancer, cervical cancer, or
carcinoma in situ of the breast, are not excluded.
3. The last systemic anti-tumor therapy, including chemotherapy and radiotherapy,
immunotherapy, targeted therapy (small molecule targeted therapy is within 2 weeks
before the first drug administration), and biologic therapy, was received within 3
weeks before the first drug administration; Palliative local treatment for
non-target diseases and foci was performed within 2 weeks before the first
administration; Received systemic non-specific immunomodulatory therapy (e.g.,
interleukin, interferon, thymosin, etc.) within 2 weeks prior to initial
administration; Received Chinese herbal medicine or proprietary Chinese medicine
with anti-tumor indications within 2 weeks prior to the first administration。
4. Previously received immunotherapy other than PD-1/PD-L1 inhibitors, including immune
checkpoint inhibitors (such as anti-CTLA-4 antibodies, anti-CD47 antibodies,
anti-SIRP-α antibodies, anti-LAG-3 antibodies, etc.), immune checkpoint agonists,
and immune cell therapy Any treatment targeting the immune mechanism of tumor
action.
5. Taxoids have been used in anti-tumor therapy in the past (including chemotherapy
drugs such as paclitaxel and docetaxel)..
6. HER-2 overexpression (immunohistochemistry 2+ and FISH+, and immunohistochemistry
3+) did not use anti-HER-2 therapy (including trastuzumab, etc.) in previous
anti-tumor therapy.
7. Any of the following has occurred during previous treatment with PD-1/PD-L1
inhibitors:
(1)There has been a history of grade 3 or higher irAE(excluding endosecretory
system-related irAE) from PD-1/PD-L1 inhibitor therapy that resulted in permanent
discontinuance of therapy, grade 2 immune-related cardiotoxicity, or any grade of
neurological or ocular irAE; (2)Prior to screening in this study, subjects who were
treated with prior PD-1/PD-L1 inhibitors and did not have complete remission of all
adverse events or did not have remission to grade 1 were admitted to the study if their
condition was stable and asymptomatic with appropriate alternative therapy; (3)Previous
adverse events requiring immunosuppressant therapy other than glucocorticoids or
recurrent adverse events during prior immunotherapy requiring systemic glucocorticoid
therapy.
8. People with active autoimmune diseases that have required systemic treatment within
the past two years (such as treatment with disease-modifying drugs, corticosteroids,
immunosuppressive agents) and replacement therapy (such as thyroxine, islet, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency) are not considered a systemic treatment.
9. Subjects with known active or untreated brain metastases, meningeal metastases,
spinal cord compression, or pIA disease are admitted if they meet the following
requirements and have measurable lesions outside the central nervous system:
Asymptomatic after treatment, radiologically stable for at least 4 weeks prior to
the start of study therapy (e.g. no new or enlarged brain metastases), and systemic
glucocorticoid and anticonvulsant therapy have been discontinued for at least 2
weeks.
10. The presence of pleural effusion, pericardial effusion or peritoneal effusion with
clinical symptoms requiring diuretic treatment and/or repeated drainage.
11. Clinically significant gastrointestinal obstruction, gastrointestinal perforation,
intraperitoneal abscess, and fistula formation occurred within 6 months before first
administration.
12. The presence of active or recurrent inflammatory gastrointestinal diseases (e.g.
Crohn's disease ulcerative colitis radiation enteritis hemorrhagic enteritis chronic
diarrhea, etc.) 13. History of myocarditis, cardiomyopathy, and malignant
arrhythmias, Unstable angina pectoris requiring hospitalization, myocardial
infarction, congestive heart failure (grade 2 or higher as defined by the New York
Heart Association Functional Scale), or vascular disease (such as risk of rupture)
in the 12 months prior to initial administration Aneurysms), or other heart damage
that may affect the safety evaluation of the investigational drug (e.g., poorly
controlled arrhythmias, myocardial ischemia).
14. Severe infection within 4 weeks prior to initial dosing, including but not limited
to comorbiditic sepsis or severe pneumonia that requires hospitalization; Active
infections that have received systemic anti-infective therapy within 2 weeks prior
to initial dosing (excluding antiviral therapy for hepatitis B or C) 15. Subjects
with known active tuberculosis (TB) and suspected active TB should be clinically
screened for exclusion; Known active syphilis infection 16. Subjects with current
active hepatitis B (HBsAg positive with more than 1000 copies /ml(200 IU/ml) of
HBV-DNA or higher than the lower limit of detection, whichever is higher) are
required to receive anti-HBV therapy during the study treatment for those with
hepatitis B; Active hepatitis C subjects (HCV antibody positive with HCV-RNA levels
above the lower limit of detection).
17. Subjects with current active hepatitis B (HBsAg positive with more than 1000 copies
/ml(200 IU/ml) of HBV-DNA or higher than the lower limit of detection, whichever is
higher) are required to receive anti-HBV therapy during the study treatment for
those with hepatitis B; Active hepatitis C subjects (HCV antibody positive with
HCV-RNA levels above the lower limit of detection).
18. The history of allogeneic organ transplantation and allogeneic hematopoietic stem
cell transplantation is known 19.No remission of toxicity from prior antitumor
therapy, defined as toxicity not returning to the level specified in the NCI CTCAE
Version 5.0, level 0 or level 1, or in the inclusion/exclusion criteria, except for
hair loss in subjects who develop irreversible toxicity and are not expected to be
aggravated after administration of the investigational drug (e.g., hearing loss)
After consultation, subjects may be included in the study of long-term toxicity
caused by radiation therapy, and those who are judged by the investigator to be
unable to recover may be included in the study.
20.Known allergy to any component of any investigational drug; There is a known history
of severe hypersensitivity to other monoclonal antibodies.
21.If a live or attenuated vaccine has been administered within 30 days prior to the
first dose, or if a live or attenuated vaccine is planned to be administered during the
study period, inactivated vaccine use is permitted.
22.Known history of mental illness substance abuse alcohol or drugs 23. Pregnant or
lactating women 24.The presence of any past or current abnormality in laboratory tests
for treatment of disease that may confuse the study results, affect the subject's full
participation in the study, or that participation in the study may not be in the
subject's best interest.
25.Local or systemic diseases caused by non-malignant tumors; Or disease or symptoms
secondary to the tumor that may lead to higher medical risk and/or uncertainty in the
evaluation of survival, such as tumor leukemia-like reactions, manifestations of
cachexia, etc 26.Any condition that the investigator believes may cause the subject to
receive the study drug treatment to be at risk of interfering with the evaluation of the
study drug, or affecting the interpretation of the study results。
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
Accepts Healthy Volunteers
Start date:
November 1, 2023
Completion date:
August 1, 2026
Lead sponsor:
Agency:
China Medical University, China
Agency class:
Other
Source:
China Medical University, China
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06118645
