Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0VHRBL
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| ADC Name |
Misitatug blivedotin
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| Synonyms |
misitatug blivedotin; RC88
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| Organization |
RemeGen (Originator)
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| Drug Status |
Phase 2 (discontinued)
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| Drug-to-Antibody Ratio |
~4
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| Structure |
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| Antibody Name |
Misitatug
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Antibody Info | ||||
| Antigen Name |
Mesothelin (MSLN)
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Antigen Info | ||||
| Payload Name |
MMAE
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Payload Info | ||||
| Therapeutic Target |
Microtubule (MT)
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Target Info | ||||
| Linker Name |
PY-MAA-Val-Cit-PABC
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Linker Info | ||||
| Conjugate Type |
Reactive Cysteines
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| Combination Type |
blivedotin
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The indication landscape of This ADC(2027 Update)
The clinical trial pipeline of This ADC(2027 Update)
| Indication | Phase 1 | Phase 1/2 | Phase 2 | Phase 2/3 | Phase 3 | New Drug Application | Approved | ||||
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| Gastric cancer |
1 Trials
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| Pancreatic cancer |
1 Trials
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| Lung cancer |
1 Trials
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| Pleura mesothelioma |
1 Trials
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| Peritoneal cancer |
1 Trials
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| Breast cancer |
1 Trials
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| Ovarian cancer |
1 Trials
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1 Trials
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| Fallopian tube cancer |
1 Trials
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| Unspecific solid tumor |
2 Trials
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General Information of The ADMET Data Related to This ADC(2027 Update)
Absorption
| Standard Type | Value | Units | Description | Reference |
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| Maximum Observed Concentration (Cmax) | 14.7±1.82 | ug/mL |
PK exposure parameters in Monkey, 0.5 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 332±33.7 | ug*h/mL |
PK exposure parameters in Monkey, 0.5 mg/kg, AUClast.
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| Maximum Observed Concentration (Cmax) | 42.8±5.09 | ug/mL |
PK exposure parameters in Monkey, 1.5 mg/kg.
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| Area Under the Concentration-Time Curve (AUC) | 1097±196 | ug*h/mL |
PK exposure parameters in Monkey, 1.5 mg/kg, AUClast.
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| Maximum Observed Concentration (Cmax) | 132±7.74 | ug/mL |
PK exposure parameters in Monkey, 5 mg/kg.
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| Area Under the Concentration-Time Curve (AUC) | 5777±560 | ug*h/mL |
PK exposure parameters in Monkey, 5 mg/kg, AUClast.
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| Maximum Observed Concentration (Cmax) | 9.12 | ug/mL |
PK exposure parameters in Mouse, 0.7 mg/kg.
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| Area Under the Concentration-Time Curve (AUC) | 418 | ug*h/mL |
PK exposure parameters in Mouse, 0.7 mg/kg, AUClast.
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| Maximum Observed Concentration (Cmax) | 36.5 | ug/mL |
PK exposure parameters in Mouse, 2.1 mg/kg.
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| Area Under the Concentration-Time Curve (AUC) | 2118 | ug*h/mL |
PK exposure parameters in Mouse, 2.1 mg/kg, AUClast.
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Distribution
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 332±33.7 | ug*h/mL |
PK exposure parameters in Monkey, 0.5 mg/kg, AUClast.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 1097±196 | ug*h/mL |
PK exposure parameters in Monkey, 1.5 mg/kg, AUClast.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 5777±560 | ug*h/mL |
PK exposure parameters in Monkey, 5 mg/kg, AUClast.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 418 | ug*h/mL |
PK exposure parameters in Mouse, 0.7 mg/kg, AUClast.
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| Area Under the Concentration-Time Curve (AUC) | 2118 | ug*h/mL |
PK exposure parameters in Mouse, 2.1 mg/kg, AUClast.
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Metabolism
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 332±33.7 | ug*h/mL |
PK exposure parameters in Monkey, 0.5 mg/kg, AUClast.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 1097±196 | ug*h/mL |
PK exposure parameters in Monkey, 1.5 mg/kg, AUClast.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 5777±560 | ug*h/mL |
PK exposure parameters in Monkey, 5 mg/kg, AUClast.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 418 | ug*h/mL |
PK exposure parameters in Mouse, 0.7 mg/kg, AUClast.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 2118 | ug*h/mL |
PK exposure parameters in Mouse, 2.1 mg/kg, AUClast.
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Excretion
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 332±33.7 | ug*h/mL |
PK exposure parameters in Monkey, 0.5 mg/kg, AUClast.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 1097±196 | ug*h/mL |
PK exposure parameters in Monkey, 1.5 mg/kg, AUClast.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 5777±560 | ug*h/mL |
PK exposure parameters in Monkey, 5 mg/kg, AUClast.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 418 | ug*h/mL |
PK exposure parameters in Mouse, 0.7 mg/kg, AUClast.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 2118 | ug*h/mL |
PK exposure parameters in Mouse, 2.1 mg/kg, AUClast.
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General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Full List of Activity Data of This Antibody-drug Conjugate
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [2] | ||||
| Patients Enrolled |
Additional exclusions include untreated brain metastases, HBV/HCV/HIV positivity (unless controlled), recent live vaccines, allergies to RC88 or excipients, and pregnancy/lactation. Subjects with psychiatric/substance abuse issues or poor compliance are also excluded, per investigator judgment.
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| Administration Dosage |
Participants will receive RC88 2.0 mg/kg every 3 weeks (Q3W)
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| Related Clinical Trial | |||||
| NCT Number | NCT06173037 | Clinical Status | PHASE2 | ||
| Clinical Description | A Multicenter, Single-arm, Phase 2 Study to Evaluate the Efficacy, Safety and Pharmacokinetics of RC88 Monotherapy in Platinum-resistant Recurrent Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Cancer | ||||
| Primary Endpoint |
The study evaluates Overall Response Rate (ORR) by both IRC and investigators using RECIST v1.1, along with Duration of Response (DOR) and Progression-free Survival (PFS) assessed by both parties. Additionally, it measures Overall Survival (OS), CA-125 levels via GCIG criteria, and pharmacokinetic parameters like RC88 binding antibody concentrations (ADC, TAb, free MMAE). Safety assessments include adverse events, lab abnormalities, and ADA/NAb incidence over approximately 2 years.
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| Other Endpoint |
Eligible subjects must be ≥18 years old with histologically confirmed high-grade serous ovarian, fallopian tube, or peritoneal cancer, platinum-resistant, and progressed after ≥3 prior therapies. Key requirements include measurable lesions (RECIST v1.1), ECOG 0-1, adequate organ function, and contraception use. Exclusion criteria encompass uncontrolled effusions, active infections, recent systemic therapies, prior mesothelin/MMAE-targeting treatments, significant comorbidities (e.g., uncontrolled cardiovascular disease, interstitial lung disease), and conditions affecting safety or compliance.
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| Experiment 2 Reporting the Activity Date of This ADC | [3] | ||||
| Patients Enrolled |
Eligibility includes age 18-70 (Phase I) or ≥18 (Phase IIa), ECOG 0-1, MSLN+ tumors, adequate organ function. Exclusions cover recent therapies, unresolved toxicity >Grade 1, active infections, cardiovascular/ocular conditions, CNS metastases, pregnancy, or protocol non-compliance.
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| Administration Dosage |
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
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| Related Clinical Trial | |||||
| NCT Number | NCT04175847 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description | To Evaluate the Safety of RC88 for Injection in Patients with Advanced Malignant Solid Tumors,Multicenter, Open, Multi-cohort Extension of Efficacy and Pharmacokinetic Characteristics Phase I /IIa Clinical Study | ||||
| Primary Endpoint |
The study evaluates Phase 1 adverse events via NCI-CTCAE v4.03 from consent to 28 days post-treatment, determines MTD of RC88 as the dose where ≥2/6 patients experience DLT within 21 days, and Phase 2 assesses ORR via IRC over 24 weeks.
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| Other Endpoint |
Phase 1 tracks ORR (CR+PR), PFS (RECIST v1.1 progression/death), and PK parameters (Cmax, Tmax, AUC, Ctrough, t1/2, CL) for TAb, ADC, and MMAE across cycles, with immunogenicity testing for anti-RC88 antibodies from Cycle 1-3.
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| Experiment 3 Reporting the Activity Date of This ADC | [4] | ||||
| Patients Enrolled |
Eligible patients are ≥18 years with ECOG 0-1, MSLN-positive advanced/metastatic solid tumors (Phase I: failed standard therapy; Phase II: confirmed MSLN+). Exclusions include brain metastases, active HBV/HCV, recent major surgery, uncontrolled cardiac conditions, or allergy to study drug components.
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| Administration Dosage |
Subjects will receive intravenous infusion of RC88 once every 2 weeks in a dose escalation fashion until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product (IMP) occurs.
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| Related Clinical Trial | |||||
| NCT Number | NCT05508334 | Clinical Status | PHASE1 | ||
| Clinical Description | An Open-label, Non-randomised, Multicentre Study to Allow Continued Access to and Assess the Safety and Tolerability of RC88 for Patients with Advanced Solid Tumours | ||||
| Primary Endpoint |
The study evaluates the recommended Phase 2 dose (RP2D) of RC88 by assessing dose-limiting toxicity (DLT) incidence within 28 days of initial treatment.
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| Other Endpoint |
Key outcomes include 24-month Objective Response Rate (ORR, CR/PR rates), measured PK parameters (Cmax, t½), and Progression-Free Survival (PFS) per RECIST v1.1 criteria across dose escalation and expansion phases.
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| Experiment 4 Reporting the Activity Date of This ADC | [5] | ||||
| Patients Enrolled |
Exclusions include brain metastases, active/hepatitis infections, recent major surgery, uncontrolled heart conditions, and allergies to mesothelin antibodies/tubulysin/mAb-related compounds, ensuring participant safety and protocol compliance.
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| Administration Dosage |
1.5mg/kg ,2.0mg/kg ,2.5mg/kg by intravenous (IV) infusion,every 3 weeks
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| Related Clinical Trial | |||||
| NCT Number | NCT05804526 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description | An Open-label, Non-randomised, Multi-center Study to Evaluate the Safety, and Efficacy Off RC88 Combined With Sintilimab in AdvancedSolid Tumours | ||||
| Primary Endpoint |
The study evaluates RP2D within 28 days post-treatment and assesses DLT incidence of RC88 combined with Sintilimab, while monitoring ORR over 24 months based on CR/PR rates and measuring RC88's Cmax at specified intervals during dose escalation.
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| Other Endpoint |
PFS is tracked for 24 months, calculated from treatment initiation to disease progression or death. Inclusion requires consent, ECOG 0/1, ≥12-week survival, MSLN positivity (Phase I), adequate organ function, and contraception adherence, with some MSLN testing exemptions for advanced cancers.
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| Experiment 5 Reporting the Activity Date of This ADC | [6] | ||||
| Patients Enrolled |
Exclusions include pregnancy, active HBV/HIV, recent live vaccines, prior immune checkpoint toxicity, uncontrolled systemic/autoimmune diseases, bleeding risks, interstitial lung disease, or significant cardiac/metastatic history. Cohort-specific exclusions: non-eligible NSCLC/cervical/gastric/ovarian cancer subtypes, prior docetaxel/VEGF/ADC use, or recent major surgery. Central nervous system metastases require stability ≥28 days post-treatment.
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| Administration Dosage |
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| Related Clinical Trial | |||||
| NCT Number | NCT06016062 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description | A Multi-center Phase I/II Trial to Evaluate the Efficacy and Safety of RC148 As a Single Agent and Combination Therapy in Patients with Locally Advanced Unresectable or Metastatic Malignant Solid Tumors | ||||
| Primary Endpoint |
Phase I evaluates MTD/MAD and DLT incidence within 28 days post-treatment, alongside AE assessment per NCI-CTCAE v5.0 until 28/90 days post-treatment, while RP2D is determined via safety committee consensus. Phase II assesses ORR, DCR, DoR, and PFS per RECIST v1.1 over 15 months.
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| Other Endpoint |
Phase I tracks ORR, DCR, DoR, and PFS over 15 months, alongside RC148 pharmacodynamics (PD-1 receptor occupancy, VEGF levels) and PK/ADA analysis. Phase II monitors AE severity (NCI-CTCAE v5.0), vital signs, and ECOG status. Key inclusion: age ≥18 (Phase I) or 18-75 (Phase II), ECOG 0/1, measurable lesions (RECIST v1.1), and organ function criteria (ANC ≥1.5×10^9/L, bilirubin ≤1.5×ULN, LVEF ≥50%).
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| Experiment 6 Reporting the Activity Date of This ADC | [7] | ||||
| Patients Enrolled |
Patients with malignant pleural mesothelioma and MSLN in advanced malignant solid tumors.
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| Administration Dosage |
Dose of 0.10, 0.50, 1.00, 1.50, 2.00 and 2.50 mg/kg.
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| Related Clinical Trial | |||||
| NCT Number | NCT04175847 | Clinical Status | Phase 1/2 | ||
| Clinical Description | To evaluate the safety of RC88 for injection in patients with advanced malignant solid tumors, multicenter, open, multi-cohort extension of efficacy and pharmacokinetic characteristics phase 1 /2a clinical study. | ||||
| Experiment 7 Reporting the Activity Date of This ADC | [8] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT04175847 | Clinical Status | Phase 1/2 | ||
| Clinical Description | To evaluate the safety of RC88 for injection in patients with advanced malignant solid tumors, multicenter, open, multi-cohort extension of efficacy and pharmacokinetic characteristics phase 1 /2a clinical study. | ||||
| Experiment 8 Reporting the Activity Date of This ADC | [9] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT05508334 | Clinical Status | Phase 1 | ||
| Clinical Description | An open-label, non-randomised, multicentre study to allow continued access to and assess the safety and tolerability of RC88 for patients with advanced solid tumours. | ||||
References