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 study testing RC48-ADC and RC98 in people with Gastric Cancer, run by RemeGen Co., Ltd. at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Trial 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… Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Gastric Cancer
What is being tested?: RC48-ADC and RC98
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 24 participants
Where: 1 siteChina
Study dates: 28 Sep 2022to 30 Sep 2024
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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;

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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.

Who cannot join

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);

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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;
Previously received PD-(L)1 inhibitor or other antibody-conjugated drug therapy;
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;
Women who are pregnant or breastfeeding or women/men who are planning to give birth;
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
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;
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);
Received chemotherapy and radiotherapy within 4 weeks before the start of the study drug;
Subjects who have received immune-enhancing therapy (such as alpha-interferon, interleukin-2) within 2 weeks before the start of the study drug.
Received hormone therapy for the tumor within 2 weeks before the start of the study drug;
Received palliative radiotherapy for bone metastases within 2 weeks before the start of the study drug;
Received anti-tumor traditional Chinese medicine treatment within 2 weeks before the start of the study drug;
The toxicity caused by previous anti-tumor therapy has not recovered to CTCAE (version 5.0) grade 0-1 (except for 2nd degree alopecia);

Trial locations and contacts

1 site in 1 country.

Jianming Fang, ph.D contact

+8610-58075763

jianmingfang@hotmail.com

China1 site, 1 recruiting

Remegen
Beijing, Beijing Municipality
Jianming Fang, Ph.D, 8610-58075763, jianminfang@hotmail.com
Ph.D
Recruiting

Other trials in China

About this study

Official title: A Phase I Clinical Study 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).

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.

Conditions: Gastric Cancer
Being tested: RC48-ADC, RC98
Medical subject headings: Stomach Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RC48-ADCDrug
Also called RC48-ADC injection
RC48 for injection is a novel antibody-drug conjugate, with a her-2-targeting antibody and a microtube inhibitor
RC98Drug
Also called RC98 injection
RC98 is a recombinant humanized IgG1 monoclonal antibody targeting programmed cell death-Ligand 1 (PD-L1)

Study groups in NCT05514158
Study group	Role	What they receive
RC48 combind with RC98	Experimental	Not described Receives: Drug: RC48-ADC; Drug: RC98

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (12)

Cmax of RC48
Peak Plasma Concentration of RC48
Measured: 24 months
AUC of RC48
Area under the plasma concentration versus time curve of RC48
Measured: 24 months
Cmax of RC98
Peak Plasma Concentration of RC98
Measured: 24 months
AUC of RC98
Area under the plasma concentration versus time curve of RC98
Measured: 24 months
AUC of MMAE
Area under the plasma concentration versus time curve of MMAE
Measured: 24 months
Cmax of MMAE
Peak Plasma Concentration of MMAE
Measured: 24 months
Immunogenicity of RC48
Anti-drug antibody (ADA) of RC48 positive samples, etc.
Measured: 24 months
Immunogenicity of RC98
Anti-drug antibody (ADA) of RC98 positive samples, etc.
Measured: 24 months
Objective response rate (ORR)
Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR)
Measured: 24 months
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
Measured: 24 months
Disease Control Rate(DCR)
Proportion of patients whose tumors shrank or stabilized for a certain period of time
Measured: 24 months
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
Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Sep 202230 Sep 2024

First posted24 Aug 2022
Study start28 Sep 2022
Primary completion30 May 2024 (estimated)
Study completion30 Sep 2024 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Gastric CancerStudies of the same condition, open and under way.
More trials run by RemeGen Co., Ltd.The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 24 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05514158
Sponsor's protocol ID: RC48-C015
Status last verified: Dec 2023
First submitted: 4 Aug 2022
Last updated: 18 Dec 2023
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Study at a glance

From the registry record, last updated by the sponsor on 18 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I Clinical Study 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).
ClinicalTrials.gov ID: NCT05514158
Acronym / sponsor ID: RC48-C015
Conditions: Gastric Cancer
Phase: Phase 1
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 24 participants (estimated)
Lead sponsor: RemeGen Co., Ltd.Industry (pharma, biotech, devices)
Study start: 28 Sep 2022 (actual)
Primary completion: 30 May 2024 (estimated)
Study completion: 30 Sep 2024 (estimated)
First posted: 24 Aug 2022 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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:

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
RC48 combind with RC98	Experimental	Drug: RC48-ADC, Drug: RC98

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (16 listed)

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;

Key exclusion criteria (27 listed)

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.);

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
RC48-ADCAlso: RC48-ADC injectionRC48 for injection is a novel antibody-drug conjugate, with a her-2-targeting antibody and a microtube inhibitor	Drug	RC48 combind with RC98
RC98Also: RC98 injectionRC98 is a recombinant humanized IgG1 monoclonal antibody targeting programmed cell death-Ligand 1 (PD-L1)	Drug	RC48 combind with RC98

Primary outcome

Dose limiting toxicity (DLT)
Time frame: 28 days after first treatment
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
The incidence and severity of adverse events (AE)
Time frame: From the day of ICF sign to 28 days after the day of the last treatment
Adverse events was assessed by investigator(s) according to NCI-CTCAE v5.0

12 secondary outcomes

Cmax of RC48
Time frame: 24 months
AUC of RC48
Time frame: 24 months
Cmax of RC98
Time frame: 24 months
AUC of RC98
Time frame: 24 months
AUC of MMAE
Time frame: 24 months
Cmax of MMAE
Time frame: 24 months
Immunogenicity of RC48
Time frame: 24 months
Immunogenicity of RC98
Time frame: 24 months
Objective response rate (ORR)
Time frame: 24 months
Duration of Remission (DOR)
Time frame: 24 months
Disease Control Rate(DCR)
Time frame: 24 months
Progression-free survival
Time frame: 24 months

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2023.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Jianming Fang, ph.D contact

+8610-58075763

jianmingfang@hotmail.com

yi Ba, ph.D principal investigator

Tianjin Cancer Hospital Airport Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing RC48-ADC and RC98 in people with Gastric Cancer, run by RemeGen Co., Ltd. at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 18 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Jianming Fang, ph.D (+8610-58075763, jianmingfang@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose limiting toxicity (DLT) (time frame: 28 days after first treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05514158.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2023.