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This was a multicenter, open, multi-cohort extended PHASE I/IIa study, consisting of 2 phases:Phase I (Phase I dose escalation) and Phase II (Phase IIa multi-cohort extension). The objective of this study was to evaluate safety, tolerability, pharmacokinetic characteristics, and initial efficacy in malignant pleural mesothelioma and MSLN in advanced malignant solid tumors.
Phase I dose escalation phase:This study predicted a total of 6 dose groups, 0.1, 0.5, 1.0, 1.5, 2.0 and 2.5 mg/kg.
Phase IIa efficacy exploration phase:This phase is the multi-cohort indication expansion phase. Based on the data obtained in phase I, chose an appropriate dose continue to explore multi-cohort indications, including confirmed malignancy Pleural mesothelioma and MSLN expression were determined.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| RC88 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RC88 | Drug | Phase I:Participants will be allocated to one of the following dose groups: 0.1, 0.5, 1.0, 1.5, 2.0 and 2.5 mg/kg, and receive a treatment of RC88-ADC followed by 21 days of dose limited toxicity (DLT) observation period. Phase IIa indication exploration |
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1 Adverse events | Adverse events was assessed by investigator(s) according to NCI-CTCAE v4.03 | From the day of ICF sign to 28 days after the day of the last treatment |
| Phase 1 Maximum Tolerated dose of RC88 | 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. |
| Phase2 | ORR is evaluated by IRC | 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1 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 |
| Phase 1 Progression Free Survival (PFS) |
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Inclusion Criteria:
Exclusion Criteria:
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| 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 |
| Phase 1 and Phase2 Pharmacokinetics (PK) parameter for total antibody (TAb): Maximum concentration (Cmax) | Cmax will be derived from the PK blood samples collected. | Phase 1:Cycle 1 and Cycle 3 (each cycle is 21 days): pre-dose, 0.5 hour (hr), 1 hr, 1.5 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 120 hrs, 168 hrs, 240 hrs (and 336 hrs) after start of infusion. Cycle 2: pre-dose.Phase2 (Whole test cycle) |
| Phase 1 and Phase2 PK parameter for TAb: Time to maximum concentration (Tmax) | Tmax will be derived from the PK blood samples collected. | Cycle 1 and Cycle 3 (each cycle is 21 days): pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 120 hrs, 168 hrs, 240 hrs (and 336 hrs) after start of infusion. Cycle 2: pre-dose.Phase2 (Whole test cycle) |
| Phase 1 PK parameter for TAb: Area under the concentration-time curve (AUC) | AUC will be derived from the PK blood samples collected. | Cycle 1 and Cycle 3 (each cycle is 21 days): pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 120 hrs, 168 hrs, 240 hrs (and 336 hrs) after start of infusion. Cycle 2: pre-dose. |
| Phase 1 PK parameter for TAb: Trough concentration (Ctrough) | Ctrough will be derived from the PK blood samples collected. | Cycle 1 and Cycle 3 (each cycle is 21 days): pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 120 hrs, 168 hrs, 240 hrs (and 336 hrs) after start of infusion. Cycle 2: pre-dose. |
| Phase 1 PK parameter for TAb: Terminal or apparent terminal half-life (t1/2) | t1/2 will be derived from the PK blood samples collected. | Cycle 1 and Cycle 3 (each cycle is 21 days): pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 120 hrs, 168 hrs, 240 hrs (and 336 hrs) after start of infusion. Cycle 2: pre-dose. |
| Phase 1 PK parameter for TAb: Systemic clearance (CL) | CL will be derived from the PK blood samples collected. | Cycle 1 and Cycle 3 (each cycle is 21 days): pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 120 hrs, 168 hrs, 240 hrs (and 336 hrs) after start of infusion. Cycle 2: pre-dose. |
| Phase 1 PK parameter for antibody-drug conjugate (ADC): Cmax | Cmax will be derived from the PK blood samples collected. | Cycle 1 and Cycle 3 (each cycle is 21 days): pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 120 hrs, 168 hrs, 240 hrs (and 336 hrs) after start of infusion. Cycle 2: pre-dose. |
| Phase 1 PK parameter for ADC: Tmax | Tmax will be derived from the PK blood samples collected. | Cycle 1 and Cycle 3 (each cycle is 21 days): pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 120 hrs, 168 hrs, 240 hrs (and 336 hrs) after start of infusion. Cycle 2: pre-dose. |
| Phase 1 PK parameter for ADC: AUC | AUC will be derived from the PK blood samples collected. | Cycle 1 and Cycle 3 (each cycle is 21 days): pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 120 hrs, 168 hrs, 240 hrs (and 336 hrs) after start of infusion. Cycle 2: pre-dose. |
| Phase 1 PK parameter for ADC: Ctrough | Ctrough will be derived from the PK blood samples collected. | Cycle 1 and Cycle 3 (each cycle is 21 days): pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 120 hrs, 168 hrs, 240 hrs (and 336 hrs) after start of infusion. Cycle 2: pre-dose. |
| Phase 1 PK parameter for ADC: t1/2 | t1/2 will be derived from the PK blood samples collected. | Cycle 1 and Cycle 3 (each cycle is 21 days): pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 120 hrs, 168 hrs, 240 hrs (and 336 hrs) after start of infusion. Cycle 2: pre-dose. |
| PK parameter for ADC: CL | CL will be derived from the PK blood samples collected. | Cycle 1 and Cycle 3 (each cycle is 21 days): pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 120 hrs, 168 hrs, 240 hrs (and 336 hrs) after start of infusion. Cycle 2: pre-dose. |
| PK parameter for Monomethyl Auristatin E (MMAE): Cmax | Cmax will be derived from the PK blood samples collected. | Cycle 1 and Cycle 3 (each cycle is 21 days): pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 120 hrs, 168 hrs, 240 hrs (and 336 hrs) after start of infusion. Cycle 2: pre-dose. |
| PK parameter for MMAE: Tmax | Tmax will be derived from the PK blood samples collected. | Cycle 1 and Cycle 3 (each cycle is 21 days): pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 120 hrs, 168 hrs, 240 hrs (and 336 hrs) after start of infusion. Cycle 2: pre-dose. |
| PK parameter for MMAE: AUC | AUC will be derived from the PK blood samples collected. | Cycle 1 and Cycle 3 (each cycle is 21 days): pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 120 hrs, 168 hrs, 240 hrs (and 336 hrs) after start of infusion. Cycle 2: pre-dose. |
| PK parameter for MMAE: Ctrough | Ctrough will be derived from the PK blood samples collected. | Cycle 1 and Cycle 3 (each cycle is 21 days): pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 120 hrs, 168 hrs, 240 hrs (and 336 hrs) after start of infusion. Cycle 2: pre-dose. |
| PK parameter for MMAE: t1/2 | t1/2 will be derived from the PK blood samples collected. | Cycle 1 and Cycle 3 (each cycle is 21 days): pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 120 hrs, 168 hrs, 240 hrs (and 336 hrs) after start of infusion. Cycle 2: pre-dose. |
| PK parameter for MMAE: CL | CL will be derived from the PK blood samples collected. | Cycle 1 and Cycle 3 (each cycle is 21 days): pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 120 hrs, 168 hrs, 240 hrs (and 336 hrs) after start of infusion. Cycle 2: pre-dose. |
| Immunogenicity assessment | Assessment of anti-RC88 antibodies | Cycle 1 to Cycle 3 (each cycle is 21 days): pre-dose, and 336 hrs after start of infusion (cycle 3 only). |
| Henan Cancer Hospital | Zhengzhou | Henan | 450008 | China |
| Drum Tower Hospital | Nanjing | Jiangsu | China |
| The First Hospital of Jilin University | Changchun | Jilin | 130021 | China |