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)

NCT05514158 | Unknown Phase 1

• 1 other identifier: RC48-C015
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Gastric Cancer

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicity (DLT)

  In the DLT evaluation window (observation period 1-28 days after the first administration), according to the NCI-CTCAE v5.0 grading standard, the investigator or the sponsor believes that toxic reaction which are reasonably related to RC48 and/or RC98 treatment

  28 days after first treatment

• The incidence and severity of adverse events (AE)

  Adverse events was assessed by investigator(s) according to NCI-CTCAE v5.0

  From the day of ICF sign to 28 days after the day of the last treatment

Secondary Outcomes (12)

• Cmax of RC48

  24 months

• AUC of RC48

  24 months

• Cmax of RC98

  24 months

• AUC of RC98

  24 months

• AUC of MMAE

  24 months

Study Arms (1)

RC48 combind with RC98

EXPERIMENTAL

Drug: RC48-ADC; Drug: RC98

Interventions

RC48-ADC DRUG

RC48 for injection is a novel antibody-drug conjugate, with a her-2-targeting antibody and a microtube inhibitor

Also known as: RC48-ADC injection

RC48 combind with RC98

RC98 DRUG

RC98 is a recombinant humanized IgG1 monoclonal antibody targeting programmed cell death-Ligand 1 (PD-L1)

Also known as: RC98 injection

RC48 combind with RC98

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily agree to participate in the research and sign the informed consent;
• Age 18-70 (including 18 and 70);
• Expected survival period ≥ 12 weeks;
• ECOG performance status of 0 or 1 within 3 days before the first dose of study treatment;
• 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;
• 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;
• 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;

You may not qualify if:

• The study drug has been used within 4 weeks before the start of the study drug;
• Major surgery has been performed within 4 weeks before the start of the study drug and the patient has not fully recovered;
• 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);
• 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;
• 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.);
• 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);
• 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;
• Suffering from uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung disease, interstitial lung disease, liver cirrhosis, etc.;
• Suffering from active infection requiring systemic treatment;
• History of active tuberculosis;
• Positive human immunodeficiency virus (HIV) test result;
• 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;
• 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.;
• Known to have hypersensitivity reactions or delayed allergic reactions to certain components of RC98 for injection or similar drugs;
• Those who are known to be allergic to recombinant humanized anti-HER2 monoclonal antibody-MMAE conjugate drugs and their components;

Sponsors & Collaborators

• RemeGen Co., Ltd.: lead

Study Sites (1)

Remegen

Beijing, Beijing Municipality, China

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Study Officials

• yi Ba, ph.D

  Tianjin Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jianming Fang, ph.D

CONTACT

+8610-58075763; jianmingfang@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2022
• First Posted: August 24, 2022
• Study Start: September 28, 2022
• Primary Completion: May 30, 2024
• Study Completion: September 30, 2024
• Last Updated: December 18, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)