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This study will evaluate the safety, pharmacokinetics, and effect of RC108-ADC for injeciton in subjects with c-Met positive advanced malignant solid tumors.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| RC108 | Experimental | Participants will be allocated to one of the following dose groups: 0.1, 0.3, 0.9, 1.5, 2.0, 2.5, and 3.0mg/kg, and receive a treatment of RC108-ADC followed by 21 days of dose limited toxicity (DLT) observation period. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RC108 | Drug | RC108 for injection is a novel antibody-drug conjugate, with a c-Met-targeting antibody and a microtube inhibitor. |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with adverse events | Adverse events was assessed by investigator(s) according to NCI-CTCAE v4.03 | From the day of ICF signment to 28 days after the day of the last treatment |
| Maximum Tolerated dose of RC108 | The dose level in which >= 2 out of 6 patients have dose-limiting toxicity (DLT). The MTD is defined as the previous dose level. | 21 days after first treatment. |
| 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) | 24 months |
| Progression Free Survival (PFS) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Yuankai Shi, M.D. | Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College | Beijing | Beijing Municipality | 100021 | China |
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| ID | Term |
|---|---|
| D007267 | Injections |
| ID | Term |
|---|---|
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
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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.
| 24 months |
| Pharmacokinetics (PK) parameter for total antibody (TAb): Maximum concentration (Cmax) | Cmax will be derived from the PK blood samples collected. | Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose. |
| PK parameter for TAb: Time to maximum concentration (Tmax) | Tmax will be derived from the PK blood samples collected. | Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose. |
| PK parameter for TAb: Area under the concentration-time curve (AUC) | AUC will be derived from the PK blood samples collected. | Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose. |
| PK parameter for TAb: Trough concentration (Ctrough) | Ctrough will be derived from the PK blood samples collected. | Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose. |
| PK parameter for TAb: Terminal or apparent terminal half-life (t1/2) | t1/2 will be derived from the PK blood samples collected. | Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose. |
| PK parameter for TAb: Systemic clearance (CL) | CL will be derived from the PK blood samples collected. | Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose. |
| PK parameter for antibody-drug conjugate (ADC): Cmax | Cmax will be derived from the PK blood samples collected. | Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose. |
| PK parameter for ADC: Tmax | Tmax will be derived from the PK blood samples collected. | Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose. |
| PK parameter for ADC: AUC | AUC will be derived from the PK blood samples collected. | Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose. |
| PK parameter for ADC: Ctrough | Ctrough will be derived from the PK blood samples collected. | Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose. |
| PK parameter for ADC: t1/2 | t1/2 will be derived from the PK blood samples collected. | Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose. |
| PK parameter for ADC: CL | CL will be derived from the PK blood samples collected. | Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose. |
| PK parameter for Monomethyl Auristatin E (MMAE): Cmax | Cmax will be derived from the PK blood samples collected. | Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose. |
| PK parameter for MMAE: Tmax | Tmax will be derived from the PK blood samples collected. | Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose. |
| PK parameter for MMAE: AUC | AUC will be derived from the PK blood samples collected. | Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose. |
| PK parameter for MMAE: Ctrough | Ctrough will be derived from the PK blood samples collected. | Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose. |
| PK parameter for MMAE: t1/2 | t1/2 will be derived from the PK blood samples collected. | Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose. |
| PK parameter for MMAE: CL | CL will be derived from the PK blood samples collected. | Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose. |
| Immunogenicity assessment | Assessment of anti-RC108 antibodies | Dose 1 to Dose 3: pre-dose, and 504 hours after start of infusion (Dose 3 only) |
| Hunan Cancer Hospital | Changsha | Hunan | China |
| The First Hospital of Jilin University | Changchun | Jilin | China |
| Zhejiang Cancer Hospital | Hangzhou | Zhejiang | China |