Trial Title:
DV Combined With Cadonilimab in Subjects With HER2-expressing Gastric Cancer and Gastroesophageal Junction Adenocarcinoma After Progression on First-line Therapy
NCT ID:
NCT06221748
Condition:
Gastric Cancer
Gastroesophageal Junction Adenocarcinoma
Conditions: Official terms:
Adenocarcinoma
Stomach Neoplasms
Esophageal Neoplasms
Paclitaxel
Disitamab vedotin
Conditions: Keywords:
Gastric cancer
Gastroesophageal junction adenocarcinoma
HER2- expressing
Study type:
Interventional
Study phase:
Phase 2/Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Disitamab Vedotin Injection
Description:
Phase II and III study ：2.5mg/kg, intravenous infusion，D1, every 2 weeks
Arm group label:
Disitamab Vedotin
Arm group label:
Disitamab Vedotin + Cadonilimab
Other name:
DV,RC48
Intervention type:
Drug
Intervention name:
Cadonilimab Injection
Description:
Phase II and III study ：6.0mg/kg, intravenous infusion，D1, every 2 weeks.
Arm group label:
Disitamab Vedotin + Cadonilimab
Other name:
AK104, Cadonilimab Injection
Intervention type:
Drug
Intervention name:
Paclitaxel Injection
Description:
Phase II and III study ：Calculate dosage based on body surface are,160mg/m2,intravenous
infusion，D1,D8 every 3 weeks
Arm group label:
Paclitaxel
Summary:
The purpose of this study is to evaluate the efficacy and safety of Disitamab Vedotin
Combined with Cadonilimab in subjects with HER2-expressing locally advanced or metastatic
gastric cancer and gastroesophageal junction adenocarcinoma after progression on
first-line therapy.
Detailed description:
This is an open-label, randomized, multicenter, Phase II/III Study designed to evaluate
safety and efficacy of Disitamab Vedotin Combined with Cadonilimab in subjects with
HER2-expressing locally advanced or metastatic gastric cancer and gastroesophageal
junction adenocarcinoma after progression on first-line therapy.
This clinical study was divided into two parts, phase II and III.Part I: Phase II study
primary objectives of the study are to evaluate the efficacy and safety of Disitamab
Vedotin Combined with Cadonilimab versus Disitamab Vedotin versus paclitaxel in subjects
with HER2-expressing locally advanced or metastatic gastric cancer and gastroesophageal
junction adenocarcinoma after progression on first-line therapy.
Part II: Phase III study primary objectives of the study are to evaluate the efficacy and
safety of Disitamab Vedotin Combined with Cadonilimab versus paclitaxel in subjects with
HER2-expressing locally advanced or metastatic gastric cancer and gastroesophageal
junction adenocarcinoma after progression on first-line therapy.
Tumor assessments, including radiological assessments by CT/MRI scans will be performed
at Screening and subsequently every 6 weeks (±7 days) until disease progression, death,
the start of new anticancer therapy, or patient's withdrawal of consent (whichever occurs
first).
All patients who discontinue treatment will be followed for survival every 3 months until
death, lost to follow-up, withdrawal of consent for survival follow-up, or end of study
(whichever comes first).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Voluntarily agreed to participate in the study and signed an informed consent form;
2. Age 18-75 years(both 18 and 75);
3. Expected survival ≥ 12 weeks
4. ECOG physical condition score of 0 or 1
5. Locally advanced or metastatic gastric adenocarcinoma (including adenocarcinoma of
the gastroesophageal junction) confirmed by histology and/or cytology
6. Subjects will only have failed or been intolerant to prior standard first-line
therapy (excluding paclitaxel), with no restriction on prior treatment with a
PD-1/PD-L1 inhibitor.
7. Confirmation of HER2 (IHC 1+, 2+, or 3+) and PD-L1 expression: for Phase II enrolled
subjects, results of investigator-confirmed HER2 and PD-L1 expression will be
accepted; for Phase III enrolled subjects, HER2 and PD-L1 expression will be
accepted only as results from the central laboratory.
8. Bone marrow function:
1. Hemoglobin ≥ 9 g/dL (no blood transfusion and no erythropoietin treatment
within 2 weeks prior to the examination);
2. Absolute neutrophil count ≥ 1.5 × 109/L (must not receive granulocyte
colony-stimulating factor treatment within 2 weeks prior to the examination)
3. Platelet count ≥ 90 × 109/L (no platelet transfusion or treatment with
recombinant human thrombopoietin within 2 weeks before the test);
9. Liver function (based on normal values at the Clinical Trials Center):
1. Serum total bilirubin ≤ 1.5 times the upper limit of normal (ULN);
2. Alanine aminotransferase (ALT) and Mentholatum aminotransferase (AST) ≤ 2.5 ×
ULN in the absence of hepatic metastases; ALT and AST ≤ 5 × ULN in the presence
of hepatic metastases;
10. Renal function (based on normal values at the Clinical Trials Center):
Blood creatinine ≤ 1.5 x ULN, or creatinine clearance (CrCl) ≥ 60 mL/min calculated
by the Cockcroft-Gault formula method, or measured 24-hour urine CrCl ≥ 60 mL/min;
11. Coagulation:
1. Prothrombin time (PT) ≤ 1.5 x ULN;
2. Thrombin time (TT) ≤ 1.5 × ULN;
3. Activated partial thromboplastin time (APTT) ≤ 1.5×ULN;
12. Cardiac function:
- New York Heart Association (NYHA) classification <3;
- Left ventricular ejection fraction (LVEF) ≥ 50%;
13. The subject is able to provide specimens for central laboratory testing/review (at
least 5 tissue sections) from the site of the primary or metastatic focus of the
tumor within 3 years, preferably specimens taken after failure of first-line
therapy;
14. Have at least one measurable lesion according to RECISTv1.1 criteria;
15. For female subjects: should be surgically sterilized, post-menopausal, or agree to
use a medically approved contraceptive method (e.g., IUD, birth control pills, or
condoms) for the duration of the study treatment and for 6 months after the end of
the study treatment period; must have had a negative blood pregnancy test within 7
days prior to the study drug administration and must not be breastfeeding; and must
not donate eggs for a period of 6 months from the time of signing of the informed
consent form to the time of the last administration of the study drug. No egg
donation for 6 months. For male subjects: should be surgically sterilized or agree
to use a medically approved method of contraception during and for 6 months after
the end of study treatment; no sperm donation from the time of signing the informed
consent until at least 4 months after the last dose of study drug;
16. Be able to understand the requirements of the trial and be willing and able to
comply with the trial and follow-up procedures.
Exclusion Criteria:
1. Metastatic CNS and/or meningeal carcinomatosis；
2. prior treatment with any antibody-drug conjugate including Disitamab Vedotin For
Injection; prior treatment with cardinolizumab
3. Prior anti-cancer therapy resulting in toxicity that has not recovered to CTCAE
(version 5.0) ≤ Grade 1 (except for hair loss, hyperpigmentation, or other
conditions that do not increase the risk of the subject's use of the drug determined
by the investigators;
4. Radical radiotherapy within 3 months prior to study dosing; palliative radiotherapy
2 weeks prior to dosing is permitted, at a dose that meets local diagnostic criteria
for palliative care and with radiotherapy coverage of less than 30% of the bone
marrow area;
5. Prior major surgery within 4 weeks before study dose start and incomplete recovery
6. Received a live vaccine within 28 days prior to the start of the first study dose or
plan to receive any vaccine during the study period
7. Third interstitial effusion associated with clinical symptoms or that requires
symptomatic treatment;
8. Ongoing grade ≥2 sensorimotor or motoneuropathy;
9. serum virology (based on site normal values):
1. Positive Hepatitis B virus surface antigen (HBsAg) test result with a positive
HBV DNA copy number;
2. Positive test result for Hepatitis C Antibody (HCVAb) (enrollment in the study
is only possible if the PCR test result for HCV RNA is negative);
3. Positive test result for human immunodeficiency virus antibody (HIVAb).；
10. Serious arterial/venous or cardiovascular accidents, such as deep vein thrombosis (
except asymptomatic interstitial vein thrombosis which does not require special
treatment), pulmonary embolism, cerebral infarction, cerebral hemorrhage, myocardial
infarction, angina pectoris, etc., except for lacunar cerebral infarction, which is
asymptomatic and does not require clinical intervention, have occurred in the last 6
months prior to the study drug administration;
11. Tumor lesions with bleeding tendency (e.g., presence of active ulcerated tumor
lesions with a positive fecal occult blood test, history of vomiting blood or black
stools within 2 months prior to signing the informed consent form, risk of
gastrointestinal hemorrhage in the judgment of the investigator, etc.), or receipt
of blood transfusion 4 weeks prior to study drug administration;;
12. The occurrence of an active or progressive infection requiring systemic treatment
(trial drug may be initiated 2 weeks after completion of anti-infective therapy);
13. The presence of unsteady controlled systemic disease as judged by the investigator,
including diabetes and hypertension, hepatocirrhosis, interstitial pneumonitis, and
obstructive lung disease.
14. The existence of active autoimmune disease requiring systemic therapy (e.g., use of
immunomodulatory agents, corticosteroids, or immunosuppressive agents) within 2
years prior to the start of study dosing, allowing for related replacement therapy
(e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for
renal or pituitary insufficiency);
15. Other malignancy within 5 years prior to the start of study dosing, with the
exception of the following: malignancies that are expected to resolve with treatment
(including, but not limited to, adequately treated thyroid cancer, carcinoma in situ
of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ of
the breast treated by radical surgery);
16. prior history of allogeneic hematopoietic stem cell transplantation or organ
transplantation;
17. known hypersensitivity to immunosuppressants and any other antibody-drug conjugate
and their components and any of the drugs in this study;
18. women who are pregnant or breast-feeding;
19. Any other disease, metabolic abnormality, physical examination abnormality, or
laboratory test abnormality that, in the judgment of the Investigator, gives reason
to suspect that the subject has a disease or condition that is unsuitable for the
use of the study medication, would interfere with the interpretation of the results
of the study, or puts the subject at a high risk of developing a condition;
20. subjects whose participation in this study is estimated to be insufficiently
adherent or who, in the judgment of the investigator, have other factors that make
them unsuitable for participation in this study.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Beijing Cancer Hospital
Address:
City:
Beijing
Zip:
100142
Country:
China
Status:
Recruiting
Contact:
Last name:
Lin Shen, M.D.
Investigator:
Last name:
Lin Shen, M.D
Email:
Principal Investigator
Facility:
Name:
The First Affiliated Hospital of Xiamen University
Address:
City:
Xiamen
Zip:
361003
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Feng Ye, M.D
Facility:
Name:
Harbin Medical University Cancer Hospital
Address:
City:
Ha'erbin
Zip:
150081
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Yanqiao Zhang, M.D
Facility:
Name:
The First Affiliated Hospital of Zhengzhou University
Address:
City:
Zhengzhou
Zip:
450052
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Yanru Qin, M.D
Facility:
Name:
Hubei Cancer Hospital
Address:
City:
Wuhan
Zip:
430079
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Huiting Xu, M.D
Facility:
Name:
Hunan Cancer Hospital
Address:
City:
Changsha
Zip:
410031
Country:
China
Status:
Recruiting
Contact:
Last name:
Zhenyang Liu, M.D
Facility:
Name:
Xuzhou Central Hospital
Address:
City:
Xuzhou
Zip:
221009
Country:
China
Status:
Recruiting
Contact:
Last name:
Yuan Yuan, M.D
Facility:
Name:
Shandong Cancer Hospital
Address:
City:
Jinan
Zip:
250117
Country:
China
Status:
Recruiting
Contact:
Last name:
Changzheng Li, M.D
Investigator:
Last name:
Changzheng Li
Email:
Principal Investigator
Facility:
Name:
The Affiliated Hospital of Qingdao University
Address:
City:
Qingdao
Zip:
266003
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Jing Lv, M.D
Facility:
Name:
Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Address:
City:
Shanghai
Zip:
200025
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Jun Zhang, M.D
Facility:
Name:
West China Hospital of Sichuan University
Address:
City:
Chengdu
Zip:
610041
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Hongfeng Gou, M.D
Facility:
Name:
Yunnan Cancer Hospital
Address:
City:
Kunming
Zip:
650118
Country:
China
Status:
Recruiting
Contact:
Last name:
Lin Xie, M.D
Start date:
February 22, 2024
Completion date:
December 2027
Lead sponsor:
Agency:
RemeGen Co., Ltd.
Agency class:
Industry
Source:
RemeGen Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06221748
