A Study of RC108-ADC in Subjects With Advanced Digestive System Malignant Tumor

Study Overview
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Brief Summary
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A multi-center, open-label, study designed to evaluate the preliminary efficacy, safety and pharmacokinetics of RC108 in patients with c-Me-positive advanced digestive system malignancies.

Detailed Description
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The primary purpose of this trial is to evaluate the preliminary efficacy, safety and efficacy of RC108 in patients with c-Me positive advanced gastrointestinal malignancies such as gastric, colorectal, esophageal, hepatic, pancreatic and bile duct cancers.

Official Title
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A Study to Evaluate the Efficacy, Safety and Pharmacokinetics of RC108 for Injection in the Treatment of Patients With c-Met-positiveAdvanced Digestive System Malignant Tumor

Conditions
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Digestive Cancer

Intervention / Treatment
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* Drug: RC108


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntary agreement to provide written informed consent. Male or female, aged between 18 to 75 years. Predicted survival for ≥ 12 weeks. Diagnosed with histologically or cytologically confirmed locally advanced or metastatic Digestive System Malignant Tumor. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. All female subjects will be considered to be of child-bearing potential unless they are postmenopausal, or have been sterilized surgically. Female subjects of child-bearing potential must agree to use two forms of highly effective contraception. Male subjects and their female partner who are of child-bearing potential must agree to use two forms of highly effective contraception. Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol. Adequate organ function, evidenced by the following laboratory result Participant has adequate bone marrow, renal, and hepatic function. bone marrow function: Hemoglobin ≥ 9g/dL; Absolute neutrophil count ≥ 1.5×10^9 /L Platelets ≥ 100×10^9 /L. hepatic function: Total bilirubin ≤ 1.5× ULN; AST and ALT ≤ 2.5×ULN and ≤ 5 x ULN with hepatic metastasis renal, and hepatic function: Serum creatinine ≤1.5×ULN. Cardiac ejection fraction ≥ 50%. Median QTc < 450 ms. c-Met positive as confirmed by the central laboratory. Measurable lesion according to RECIST 1.1. Exclusion Criteria: Known hypersensitivity to the components of RC108-ADC. Toxicity of previous anti-tumor treatment not recovered to CTCAE (v5.0) Grade 0-1 (with exception of Grade 2 alopecia). Uncontrolled pericardial effusion or cardiac tamponade, or pleural or abdominal effusion with clinical symptoms. History of receiving any anti-cancer drug/biologic treatment within 4 weeks prior to trial treatment. History of major surgery within 4 weeks of planned start of trial treatment. Has received a live virus vaccine within 4 weeks of planned start of trial treatment. Currently known active infection with HIV or tuberculosis. Diagnosed with HBsAg, HBcAb positive and HBV DNA copy positive, or HCVAb positive. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or cancers with a similar curative outcome as those mentioned above. Known central nervous system metastases. Uncontrolled hypertension, diabetes, pulmonary fibrosis, acute lung disease, Interstitial lung disease, or liver cirrhosis; Pregnancy or lactation. Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>gastric cancer patients | Drug: RC108<br>* RC108 is comprised of an antibody component conjoined to a drug component in a lyophilized powder, which is made into solution for intravenous administration.<br>|
| Experimental: cohort 2<br>colorectal cancer patients | Drug: RC108<br>* RC108 is comprised of an antibody component conjoined to a drug component in a lyophilized powder, which is made into solution for intravenous administration.<br>|
| Experimental: cohort 3<br>liver cancer patients | Drug: RC108<br>* RC108 is comprised of an antibody component conjoined to a drug component in a lyophilized powder, which is made into solution for intravenous administration.<br>|
| Experimental: cohort 4<br>other digestive system malignancies, including esophageal cancer, pancreatic cancer, gallbladder cancer, etc. | Drug: RC108<br>* RC108 is comprised of an antibody component conjoined to a drug component in a lyophilized powder, which is made into solution for intravenous administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR) | Up to 24 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DCR | The disease control rate is the proportion of those subjects with complete response, partial response, or stable disease, as defined by Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1) | Up to 24 Months | 
| Adverse Events | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. | Up to 24 Months | 
| DOR | DOR is defined as the time from the participant's initial objective response to study drug therapy to disease progression or death, whichever occurs first. | Up to 24 Months | 
| TTP | Time to progression will be measured from the first day of study drug until progression. | Up to 24 Months | 
| PFS | PFS time is defined as the time from the participant's first dose of RC108 to either the participant's disease progression or death, whichever occurs first. | Up to 24 Months | 
| OS | Duration from date of sub-study registration (or date of screening/pre-screening registration if patient never enrolls in a sub-study) to date of death due to any cause. | Up to 5 years | 
| Area under the curve (AUC) from time zero to the last measurable concentration AUC (0-t) | Area under the curve (AUC) from time zero to the last measurable concentration AUC (0-t) | Up to 24 Months | 
| Maximum observed plasma concentration (Cmax) | Maximum observed plasma concentration (Cmax) | Up to 24 Months | 
| Time to Cmax (Tmax) | Time to Cmax (Tmax). | Up to 24 Months | 
| Terminal elimination half life | Terminal elimination half life. | Up to 24 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Digestive Cancer