Linker Information
General Information of This Linker
| Linker ID |
LIN0DYSGZ
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| Linker Name |
PY-MAA-Val-Cit-PABC
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| Linker Type |
Cathepsin-cleavable linker
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| Antibody-Linker Relation |
Cleavable
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| Structure |
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| Formula |
C32H46N8O8S
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| Isosmiles |
C=CC(=O)N1CN(C(=O)C=C)CN(C(=O)CCSCC(=O)NC(C(=O)NC(CCCNC(N)=O)C(=O)Nc2ccc(CO)cc2)C(C)C)C1
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| InChI |
InChI=1S/C32H46N8O8S/c1-5-26(43)38-18-39(27(44)6-2)20-40(19-38)28(45)13-15-49-17-25(42)37-29(21(3)4)31(47)36-24(8-7-14-34-32(33)48)30(46)35-23-11-9-22(16-41)10-12-23/h5-6,9-12,21,24,29,41H,1-2,7-8,13-20H2,3-4H3,(H,35,46)(H,36,47)(H,37,42)(H3,33,34,48)
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| InChIKey |
HQIKSJQCJBQAKX-UHFFFAOYSA-N
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| Pharmaceutical Properties |
Molecule Weight
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702.835
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Polar area
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223.58
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Complexity
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49
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xlogp Value
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0.0587
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Heavy Count
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49
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Rot Bonds
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18
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Hbond acc
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9
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Hbond Donor
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6
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Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
Misitatug blivedotin [Phase 2 (discontinued)]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| 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
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| 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 | [2] | ||||
| 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
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| 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 | [3] | ||||
| 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
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| 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 | [4] | ||||
| 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
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| 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 | [5] | ||||
| 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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| 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
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| 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 | [6] | ||||
| 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.
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| Experiment 7 Reporting the Activity Date of This ADC | [7] | ||||
| 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.
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| Experiment 8 Reporting the Activity Date of This ADC | [8] | ||||
| 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.
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RC88-Py-MAA-Val-Cit-PAB-MMAD [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [9] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
0.043۪.011 nM
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Positive MSLN expression (MSLN+++/++) | ||
| Method Description |
Oval-Citar-3-MSLN cells with good growth state were added to 96-well cell culture plates (5×104 cells /mL, 100uL/ well) and incubated overnight in a CO2 incubator at 38°C.
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| In Vitro Model | High grade ovarian serous adenocarcinoma | Oval-Citar-3-MSLN cells | CVCL_0465 | ||
RC88-Py-MAA-Val-Cit-PAB-MMAE [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [9] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
0.093۪.009 nM
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Positive MSLN expression (MSLN+++/++) | ||
| Method Description |
Oval-Citar-3-MSLN cells with good growth state were added to 96-well cell culture plates (5×104 cells /mL, 100uL/ well) and incubated overnight in a CO2 incubator at 37°C.
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| In Vitro Model | High grade ovarian serous adenocarcinoma | Oval-Citar-3-MSLN cells | CVCL_0465 | ||
References