Trial Title:
To Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Disitamab Vedotin Combined With RC98 in the Treatment of Subjects With HER2-expressing Locally Advanced or Metastatic Gastric Cancer (Including AEG)
NCT ID:
NCT05514158
Condition:
Gastric Cancer
Conditions: Official terms:
Stomach Neoplasms
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
RC48-ADC
Description:
RC48 for injection is a novel antibody-drug conjugate, with a her-2-targeting antibody
and a microtube inhibitor
Arm group label:
RC48 combind with RC98
Other name:
RC48-ADC injection
Intervention type:
Drug
Intervention name:
RC98
Description:
RC98 is a recombinant humanized IgG1 monoclonal antibody targeting programmed cell
death-Ligand 1 (PD-L1)
Arm group label:
RC48 combind with RC98
Other name:
RC98 injection
Summary:
This is a single-center, open-label, dose-escalation phase I clinical study.This study
aimed to evaluate the safety, tolerability, pharmacokinetics and preliminary clinical
efficacy of RC48-ADC combined with RC98 in subjects with advanced gastric cancer.Which
will provide a reference basis for dose confirmation in subsequent clinical studies.
Detailed description:
The dose escalation phase will enroll subjects with HER2-expressing locally advanced or
metastatic gastric cancer, including gastroesophageal junction adenocarcinoma. HER2
expression is defined as follows (meets one of the following):
• HER2 IHC3+, 2+, 1+; (Subjects with HER2 immunohistochemistry (IHC) results of IHC1+,
IHC 2+, and IHC 3+, previous test results (confirmed by the investigator) or research
center test results are acceptable;
The dose-escalation phase preset doses for this combination therapy are as follows:
RC48-ADC: 2.5mg/kg Q2W; RC98 increasing dose: 5.0mg/kg Q2W, 10.0mg/kg Q2W, 15.0mg/kg Q2W.
The dose escalation phase of the combination therapy adopts the Bayesian optimal interval
(BOIN) design method: the fixed dose of RC48-ADC is 2.5 mg/kg, and the dose of RC98 is
escalated, and the initial incremental dose of RC98 is 5.0 mg/kg. MTD has a target
toxicity rate of 0.3 and a maximum sample size of 24. The subjects will be enrolled in
units of 3, with a maximum of 12 subjects in each dose group; the 28 days after the first
dose will be used as the observation window of DLT to make decisions such as dose
increase and decrease. If the DLT criteria were not met within 28 days after the first
dose, dose escalation was not continued to observe DLT and MTD. After the dose escalation
period is over, the investigator decides the recommended phase 2 dose (RP2D) based on the
available safety, tolerability, PK, and efficacy information.
After completing the dose-limiting toxicity (DLT) evaluation, the subject can continue to
receive the original dose of study drug treatment (but not more than the currently
ongoing escalating dose or the maximum tolerated dose under the condition that the
investigator judges that there may be benefits) ), subjects received treatment until
intolerable toxicity, disease progression, or termination of the study by the sponsor.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Voluntarily agree to participate in the research and sign the informed consent;
2. Age 18-70 (including 18 and 70);
3. Expected survival period ≥ 12 weeks;
4. ECOG performance status of 0 or 1 within 3 days before the first dose of study
treatment;
5. Patients with metastatic or unresectable locally advanced or metastatic gastric
cancer (including gastroesophageal junction adenocarcinoma) confirmed by histology
or cytology with disease progression after standard treatment or intolerant to
standard treatment;
6. Female subjects should be surgically sterilized, postmenopausal patients, or agree
to use at least one medically approved contraceptive measure (such as an
intrauterine device, contraceptives) during the study treatment period and within 6
months after the end of the study treatment period. pills or condoms), must have a
negative blood pregnancy test within 7 days prior to study enrollment, and must be
non-nursing. Male subjects should agree to use at least one medically approved
contraceptive method during the study treatment period and within 6 months after the
end of the study treatment period;
7. Able to understand trial requirements, willing and able to comply with trial and
follow-up procedures.
Adequate organ and bone marrow hematopoiesis 8. Bone marrow function:
- Hemoglobin≥90g/L;
- Absolute neutrophil count ≥1.5×109/L;
- Platelets≥100 × 109/L; 9. Liver function (subject to the normal value of the
clinical trial center):
- In the absence of liver metastases, the total serum bilirubin is ≤1.5 times the ULN;
in the presence of liver metastases, the total serum bilirubin is ≤3 times the ULN;
- In the absence of liver metastases, both ALT and AST are ≤3 times ULN, and in the
presence of liver metastases, both ALT and AST are ≤5 times ULN; 10. Renal function
(subject to the normal value of the clinical trial center):
- Serum creatinine ≤ 1.5 times ULN, or creatinine clearance (CrCl) ≥ 60 mL/min
calculated by the Cockcroft-Gault formula, or 24-hour urine CrCl ≥ 60 mL/min; 11.
Coagulation function: International normalized ratio (INR), activated partial
thromboplastin time (APTT) and prothrombin time (PT) are all ≤1.5 times ULN; 12.
Endocrine function: Thyroid-stimulating hormone (TSH) or free thyroxine (FT4) or
free triiodothyronine (FT3) are within the normal range of ±10%; 13. Heart function:
- New York Heart Association (NYHA) class <3;
- Left ventricular ejection fraction ≥50%; 14. At least one measurable lesion
according to RECIST 1.1 criteria; 15. The HER2 IHC test results are IHC 1+, IHC 2+
or IHC 3+, the subject's previous test results (confirmed by the investigator) or
the test results of the research center are acceptable, and can provide a diagnosis
of locally advanced or metastatic gastric cancer of tumor tissue specimens, as well
as a sufficient number of paraffin blocks, tissue sections (5-10 unstained) for
biomarker detection.
Exclusion Criteria:
1. The study drug has been used within 4 weeks before the start of the study drug;
2. Major surgery has been performed within 4 weeks before the start of the study drug
and the patient has not fully recovered;
3. Have been vaccinated with live vaccines within 4 weeks before the start of the study
drug or plan to receive any vaccines during the study period (except for the new
coronavirus vaccine);
4. Arterial/venous thrombotic events, such as cerebrovascular accident (including
temporary ischemic attack), deep vein thrombosis and pulmonary embolism, occurred
within 6 months before the study drug;
5. Major cardiovascular disease (NYHA grade 3 or 4 heart failure, second-degree or
higher heart block, myocardial infarction within the past 12 months, unstable
arrhythmia or unstable angina pectoris, cerebral infarction within 6 months
infarction, etc.);
6. Active autoimmune disease requiring systemic treatment (such as the use of
immunomodulatory drugs, corticosteroids or immunosuppressants) within 2 years before
the start of study administration, allowing related replacement therapy (such as
thyroxine, insulin, or renal or Physiological corticosteroid replacement therapy for
pituitary insufficiency);
7. Subjects who need to receive glucocorticoid (prednisone>10 mg/day or other similar
drugs at an equivalent dose) or other immunosuppressive therapy due to certain
conditions within 14 days before the start of the study drug;
8. Suffering from uncontrolled systemic diseases, including diabetes, hypertension,
pulmonary fibrosis, acute lung disease, interstitial lung disease, liver cirrhosis,
etc.;
9. Suffering from active infection requiring systemic treatment;
10. History of active tuberculosis;
11. Positive human immunodeficiency virus (HIV) test result;
12. Hepatitis B surface antigen (HBsAg) positive and HBV DNA copy number greater than
the upper limit of the normal value of the laboratory department of the research
center; or hepatitis C virus (HCV) antibody positive and the HCV RNA copy number
greater than the upper limit of the normal value of the laboratory department of the
research center;
13. Conditions that the investigator believes will affect the safety or compliance of
the drug treatment in this study, including but not limited to moderate to large
amounts of pleural/ascites/pericardial effusion, difficult-to-correct
pleural/ascites/pericardial effusion, mental illness, etc.;
14. Known to have hypersensitivity reactions or delayed allergic reactions to certain
components of RC98 for injection or similar drugs;
15. Those who are known to be allergic to recombinant humanized anti-HER2 monoclonal
antibody-MMAE conjugate drugs and their components;
16. Previously received PD-(L)1 inhibitor or other antibody-conjugated drug therapy;
17. Suffering from any other disease, metabolic abnormality, abnormal physical
examination or abnormal laboratory test, according to the judgment of the
investigator, there is reason to suspect that the subject has a certain disease or
condition that is not suitable for the use of the study drug, or will affect the
research results interpretations, or situations that place the subject at high risk;
18. Women who are pregnant or breastfeeding or women/men who are planning to give birth;
19. It is estimated that the subjects' compliance to participate in this clinical study
is insufficient or the investigators believe that there are other factors that are
not suitable for participating in this study; tumor related
20. Suffering from central nervous system metastases and/or cancerous meningitis.
Subjects who have previously received treatment for brain metastases may be
considered for participation in this study, provided that their disease has been
stable for at least 3 months, no disease progression has been confirmed by imaging
within 4 weeks prior to the first dose of the study, and all neurological symptoms
have recovered At baseline, there was no evidence of new or enlarging brain
metastases, and radiation, surgery, or steroid therapy was discontinued at least 28
days prior to the first dose of study treatment. This exception does not include
cancerous meningitis, which should be excluded regardless of its clinically stable
status;
21. Suffering from other malignant tumors within 5 years before signing the informed
consent form (non-melanoma skin cancer, cervical carcinoma in situ or other tumors
that have been effectively treated, except for malignant tumors that are considered
cured);
22. Received chemotherapy and radiotherapy within 4 weeks before the start of the study
drug;
23. Subjects who have received immune-enhancing therapy (such as alpha-interferon,
interleukin-2) within 2 weeks before the start of the study drug.
24. Received hormone therapy for the tumor within 2 weeks before the start of the study
drug;
25. Received palliative radiotherapy for bone metastases within 2 weeks before the start
of the study drug;
26. Received anti-tumor traditional Chinese medicine treatment within 2 weeks before the
start of the study drug;
27. The toxicity caused by previous anti-tumor therapy has not recovered to CTCAE
(version 5.0) grade 0-1 (except for 2nd degree alopecia);
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Remegen
Address:
City:
Beijing
Country:
China
Status:
Recruiting
Contact:
Last name:
Jianming Fang, Ph.D
Phone:
8610-58075763
Email:
jianminfang@hotmail.com
Contact backup:
Last name:
Ph.D
Investigator:
Last name:
yi Ba, Ph.D
Email:
Principal Investigator
Start date:
September 28, 2022
Completion date:
September 30, 2024
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/NCT05514158