CClinicalTrials.gg
RecruitingNCT05514158Updated Dec 18, 2023

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)

A Phase 1 interventional study of RC48-ADC and RC98 in Gastric Cancer, sponsored by RemeGen Co., Ltd.. Recruiting at 1 site in China. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2023-12-18.

Sponsored by RemeGen Co., Ltd. · Phase 1, Interventional, and Treatment

From the registry’s dates

  • Primary completion was expected by May 2024, 2 years 4 months ago, but the record still lists the study as recruiting.
  • Started Sep 2022; still recruiting 4 years later.
Phase
Phase 1
Study type
Interventional
Enrollment
24
Allocation
Not applicable
Ages
18 Years to 70 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Gastric Cancer

Browse trials for

03

In context

Stomach Neoplasms

2,851 studies on the registry are indexed under Stomach Neoplasms; 864 are open to participants now.

This study's planned enrollment of 24 is below the median of 67 across 2,096 interventional studies indexed under Stomach Neoplasms.

Browse Stomach Neoplasms studies →

Lead sponsor

RemeGen Co., Ltd. is the lead sponsor of 77 studies on the registry; 37 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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);
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
24 participants (estimated)

Study arms

  • Experimental
    RC48 combind with RC98

    Drug: RC48-ADC · Drug: RC98

Interventions

  • DrugRC48-ADC

    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

  • DrugRC98

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

    Also known as: RC98 injection

06

What researchers measure

Primary outcomes

  1. 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

    Time frame: 28 days after first treatment

  2. The incidence and severity of adverse events (AE)

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

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

Secondary outcomes

  1. Cmax of RC48

    Peak Plasma Concentration of RC48

    Time frame: 24 months

  2. AUC of RC48

    Area under the plasma concentration versus time curve of RC48

    Time frame: 24 months

  3. Cmax of RC98

    Peak Plasma Concentration of RC98

    Time frame: 24 months

  4. AUC of RC98

    Area under the plasma concentration versus time curve of RC98

    Time frame: 24 months

  5. AUC of MMAE

    Area under the plasma concentration versus time curve of MMAE

    Time frame: 24 months

  6. Cmax of MMAE

    Peak Plasma Concentration of MMAE

    Time frame: 24 months

  7. Immunogenicity of RC48

    Anti-drug antibody (ADA) of RC48 positive samples, etc.

    Time frame: 24 months

  8. Immunogenicity of RC98

    Anti-drug antibody (ADA) of RC98 positive samples, etc.

    Time frame: 24 months

  9. Objective response rate (ORR)

    Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR)

    Time frame: 24 months

  10. Duration of Remission (DOR)

    Duration of response is the length of time that a tumor continues to respond to treatment without the cancer growing or spreading

    Time frame: 24 months

  11. Disease Control Rate(DCR)

    Proportion of patients whose tumors shrank or stabilized for a certain period of time

    Time frame: 24 months

  12. Progression-free survival

    Progression-free Survival (PFS) (median) was determined using the number of months measured from the initial date of treatment to the date of documented progression, or the date of death (in the absence of progression) of participants. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

    Time frame: 24 months

07

Study locations

1 of 1 sites recruiting
  • Remegen
    Beijing, Beijing, China
    • Jianming Fang, Ph.D · Contact · jianminfang@hotmail.com · 8610-58075763
    • Ph.D · Contact
    • yi Ba, Ph.D · Principal investigator
    Recruiting
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 18, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT05514158
Lead sponsor
RemeGen Co., Ltd.
Responsible party
Sponsor
First posted
Aug 24, 2022
Start date
Sep 28, 2022
Primary completion
May 30, 2024 (estimated)
Completion
Sep 30, 2024 (estimated)
Last update
Dec 18, 2023

Study contacts

Jianming Fang, ph.D
Contact
jianmingfang@hotmail.com
+8610-58075763
yi Ba, ph.D
principal investigator · Tianjin Cancer Hospital

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Interested in this study?

Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.

Contact study team

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion