Linker Information
General Information of This Linker
| Linker ID |
LIN0ILPTC
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| Linker Name |
ThioBridge-PEG24-Val-Cit-PABC
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| Antibody-Linker Relation |
Cleavable
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| Structure |
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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
OBI-999 [Phase 1/2 (discontinued)]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Patients Enrolled |
Advanced solid tumors that had been previously treated with standard-of-care therapy and their physicians had determined that such therapy was no longer effective, or patients had declined to receive further standard-of-care treatments.
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| Administration Dosage |
The starting dose of 0.40 mg/kg on day 1 of each 21-day cycle; A standard 3 + 3 dose-escalation design was used, and doses of 0.80, 1.20, and 1.60 mg/kg were also administered on day 1 of each 21-day cycle; intravenous infusion over 60 minutes.
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| Related Clinical Trial | |||||
| NCT Number | NCT04084366 | Clinical Status | Phase 1 | ||
| Clinical Description |
A phase 1/2, open-label, dose-escalation and cohort-expansion study evaluating the safety, pharmacokinetics, and therapeutic activity of OBI-999 in patients with advanced solid tumors.
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| Primary Endpoint |
The incidence of dose-limiting toxicities and adverse events and determination of the maximum tolerated dose (MTD)/recommended phase II dose.
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| Experiment 2 Reporting the Activity Date of This ADC | [4] | ||||
| Patients Enrolled |
Inclusion criteria require patients aged ≥18 with advanced solid tumors (refractory to/intolerant of standard therapy), measurable disease (RECIST 1.1), ECOG 0-1, adequate organ function (ALT/AST ≤3×ULN [≤5×ULN if liver mets], bilirubin ≤1.5×ULN, ANC ≥1,500/uL, platelets ≥100,000/uL), and Globo H H-score ≥100 (Cohort-Expansion). HIV/HBV/HCV-infected patients are eligible if controlled. Exclusions include recent chemotherapy/radiation (<3 weeks), major surgery (<28 days), Grade ≥2 neuropathy, prior Globo H-targeted therapy, uncontrolled CNS metastases, cardiac dysfunction, or concurrent prohibited medications.
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| Administration Dosage |
Part A: Five cohorts at escalating dose levels 0.4, 0.8, 1.2, 1.6 and 2.0 mg/kg (capping calculations at a maximum at 100 kg) of OBI-999 liquid form via IV infusion to establish maximum tolerated dose (MTD) and Recommended phase 2 dose (RP2D).Part B: Five cohorts of patients at RP2D of OBI-999 liquid form, as determined from Part A, via IV infusion.
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| Related Clinical Trial | |||||
| NCT Number | NCT04084366 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description |
A Phase 1/2, Open-Label, Dose-Escalation and Cohort-Expansion Study Evaluating the Safety, Pharmacokinetics, and Therapeutic Activity of OBI-999 in Patients with Advanced Solid Tumors
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| Primary Endpoint |
The primary objective is to assess the clinical benefit of OBI-999 through Objective Response Rate (ORR: CR+PR) per RECIST 1.1, evaluated every 6 weeks (±7 days) during initial 3 months, then every 9 weeks (±7 days) until treatment discontinuation, progression, death, or new therapy initiation-whichever occurs first within ~2 years (up to 35 cycles).
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| Other Endpoint |
Key secondary endpoints include preliminary efficacy (ORR, Clinical Benefit Rate [CBR], Duration of Response [DOR], PFS per RECIST 1.1) and immunogenicity (anti-drug antibodies [ADAs]), analyzed from Week 1 to Week 106. Pharmacokinetics (PK) of OBI-999 and its active metabolite (MMAE) will be assessed via non-compartmental methods during Cycles 1-2, measuring Cmax, AUC, t1/2, clearance (Cl), Tmax, and volume of distribution (Vd).
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Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 34% | Positive Globo H expression (Globo H+++/++) | ||
| Method Description |
Mice were treated with an intravenous dose of the ADCs at 0.3 mg/kg, qw*6.
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| In Vivo Model | MCF-7 CDX model | ||||
| In Vitro Model | Invasive breast carcinoma | MCF-7 cells | CVCL_0031 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 60% | Positive Globo H expression (Globo H+++/++) | ||
| Method Description |
Mice were treated with an intravenous dose of the ADCs at 1 mg/kg, qw*6.
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| In Vivo Model | MCF-7 CDX model | ||||
| In Vitro Model | Invasive breast carcinoma | MCF-7 cells | CVCL_0031 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 83% | Positive Globo H expression (Globo H+++/++) | ||
| Method Description |
Mice were treated with an intravenous dose of the ADCs at 1 mg/kg, qw*4.
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| In Vivo Model | NCI-N87 CDX model | ||||
| In Vitro Model | Gastric tubular adenocarcinoma | NCI-N87 cells | CVCL_1603 | ||
| Experiment 4 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 85% | Positive Globo H expression (Globo H+++/++) | ||
| Method Description |
Mice were treated with an intravenous dose of the ADCs at 10 mg/kg, qw*4.
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| In Vivo Model | NCI-H526 CDX model | ||||
| In Vitro Model | Lung small cell carcinoma | NCI-H526 cells | CVCL_1569 | ||
| Experiment 5 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 95% | Positive Globo H expression (Globo H+++/++) | ||
| Method Description |
Mice were treated with an intravenous dose of the ADCs at 10 mg/kg, qw*2.
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| In Vivo Model | MCF-7 CDX model | ||||
| In Vitro Model | Invasive breast carcinoma | MCF-7 cells | CVCL_0031 | ||
| Experiment 6 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 97% | Positive Globo H expression (Globo H+++/++) | ||
| Method Description |
Mice were treated with an intravenous dose of the ADCs at 10 mg/kg, qw*4.
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| In Vivo Model | NCI-N87 CDX model | ||||
| In Vitro Model | Gastric tubular adenocarcinoma | NCI-N87 cells | CVCL_1603 | ||
| Experiment 7 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 97% | Positive Globo H expression (Globo H+++/++) | ||
| Method Description |
Mice were treated with an intravenous dose of the ADCs at 1-3 mg/kg, qw*4.
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| In Vivo Model | NCI-N87 CDX model | ||||
| In Vitro Model | Gastric tubular adenocarcinoma | NCI-N87 cells | CVCL_1603 | ||
| Experiment 8 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 98% | Positive Globo H expression (Globo H+++/++) | ||
| Method Description |
Mice were treated with an intravenous dose of the ADCs at 3 mg/kg, qw*6.
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| In Vivo Model | MCF-7 CDX model | ||||
| In Vitro Model | Invasive breast carcinoma | MCF-7 cells | CVCL_0031 | ||
| Experiment 9 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 99% | Positive Globo H expression (Globo H+++/++) | ||
| Method Description |
Mice were treated with an intravenous dose of the ADCs at 10 mg/kg, qw*4.
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| In Vivo Model | HPAC CDX model | ||||
| In Vitro Model | Pancreatic adenocarcinoma | HPAC cells | CVCL_3517 | ||
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 70.70% | |||
| Method Description |
In vivo , In each animal study,the antitumor efficacy was evaluated with doses of 1.00, 3.00, or 10.00 mg/kg of OBI-999 via i.v. injection. In NCI-N87 xenograft model,treatment groups of MMAE 0.191 mg/kg and Ctrl-ADC 3 mg/kg were also included. Each study utilized 6 to 8 mice per group.
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| In Vitro Model | Breast adenocarcinoma | MDA-MB-231 cells | CVCL_0062 | ||
| Breast adenocarcinoma | HCC1428 cells | CVCL_1252 | |||
References