Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0CRDKL
|
|||||
|---|---|---|---|---|---|---|
| ADC Name |
HKT288
|
|||||
| Synonyms |
HKT288; NOV-13
Click to Show/Hide
|
|||||
| Organization |
MorphoSys (Top20 MNC) (Originator);Novartis (Top20 MNC);ImmunoGen (Top20 MNC)
|
|||||
| Drug Status |
Phase 1 (discontinued)
|
|||||
| Structure |
|
|||||
|
|
||||||
| Antibody Name |
Anti-CDH6 HKT-288 mAb
|
Antibody Info | ||||
| Antigen Name |
Cadherin-6 (CDH6)
|
Antigen Info | ||||
| Payload Name |
DM4
|
Payload Info | ||||
| Therapeutic Target |
Microtubule (MT)
|
Target Info | ||||
| Linker Name |
Sulfo-SPDB
|
Linker Info | ||||
| Conjugate Type |
Random Lysines
|
|||||
| Combination Type |
soravtansine
|
|||||
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 | ||
|---|---|---|---|---|---|---|---|---|---|
| Kidney cancer |
1 Trials
|
||||||||
| Ovarian cancer |
1 Trials
|
||||||||
| Unspecific solid tumor |
1 Trials
|
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Discovered Using Cell Line-derived Xenograft Model
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 | [1] | ||||
| Patients Enrolled |
Patients with advanced solid tumors, including epithelial ovarian cancer and renal cell carcinoma.
|
||||
| Administration Dosage |
Cadherin-6-targeting ADC iv at dose of 0.30, 0.75 mg/kg.
|
||||
| Related Clinical Trial | |||||
| NCT Number | NCT02947152 | Clinical Status | Phase 1 | ||
| Clinical Description | A phase 1, multicenter, open-label dose escalation and expansion study of HKT288, administered intravenously in adult patients with advanced solid tumors, including epithelial ovarian cancer and renal cell carcinoma. | ||||
| Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
| Patients Enrolled |
Advanced (metastatic or locally advanced) serous epithelial ovarian, serous fallopian tubal or serous primary peritoneal cancer or advanced clear cell or papillary renal cell carcinoma (RCC), who had received or were intolerant to all therapies known to confer clinical benefit for their disease and Eastern Cooperative Oncology Group (ECOG) performance status 2.
Click to Show/Hide
|
||||
| Administration Dosage |
HKT288 was administered intravenously (IV) every 3 weeks until patients experienced unacceptable toxicity or progressive disease (PD). The starting dose of 0.30 mg/kg was determined based on the highest nonseverely toxic dose in monkeys, which was 2 mg/kg IV weekly.
|
||||
| Related Clinical Trial | |||||
| NCT Number | NCT02947152 | Clinical Status | Phase 1 | ||
| Clinical Description | A phase 1, multicenter, open-label dose escalation and expansion study of HKT288, administered intravenously in adult patients with advanced solid tumors, including epithelial ovarian cancer and renal cell carcinoma. | ||||
| Primary Endpoint |
The best overall response on the 0.30 mg/kg cohort in patients with measurable disease was RECIST v1.1 stable disease in 3 patients and PD in 2 patients.
|
||||
| Experiment 3 Reporting the Activity Date of This ADC | [4] | ||||
| Patients Enrolled |
Eligible patients had advanced CDH6-positive ovarian/renal cancers refractory to standard therapies (ECOG ≤2); exclusions comprised active CNS metastases, corneal disorders, QTcF >470ms, prior maytansine-ADC use, or recent anticancer treatments (chemotherapy ≤4-6 weeks, biologics ≤4 weeks, radiation ≤2-4 weeks), ensuring cohort safety.
|
||||
| Administration Dosage |
HKT288 was administered intravenously (IV) every 3 weeks until patients experienced unacceptable toxicity or progressive disease (PD). The starting dose of 0.3 mg/kg was determined based on the highest nonseverely toxic dose in monkeys, which was 2 mg/kg IV weekly.
|
||||
| Related Clinical Trial | |||||
| NCT Number | NCT02947152 | Clinical Status | PHASE1 | ||
| Clinical Description | A Phase I, Multicenter, Open-label Dose Escalation and Expansion Study of HKT288, Administered Intravenously in Adult Patients With Advanced Solid Tumors, Including Epithelial Ovarian Cancer and Renal Cell Carcinoma | ||||
| Primary Endpoint |
Safety assessments focused on dose-limiting toxicities (DLTs) during the 21-day evaluation period, while tracking adverse events (AEs) and serious AEs (SAEs) for ~6 months post-treatment, including dose modifications and severity grading to evaluate tolerability.
|
||||
| Other Endpoint |
Key endpoints included pharmacokinetic analysis (tAb concentration, AUC, Cmax, Tmax, half-life) through Cycle 6, treatment immunogenicity (anti-HKT288 antibodies), and efficacy measures (ORR, DoR, PFS, DCR) assessed via serial tumor evaluations during treatment and 12-month follow-up, alongside retrospective CDH6 expression profiling.
|
||||
Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 90% | High CDH6 expression (CDH6+++) | ||
| Method Description |
CDH6-sulfo-DM4 induces efficient tumor cell killing in cell PDX models with CDH6 expression.
|
||||
| In Vivo Model | Ovarian cancer CDX model | ||||
| In Vitro Model | Ovarian serous adenocarcinoma | OVCAR-3 cells | CVCL_0465 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 100% | High CDH6 expression (CDH6+++) | ||
| Method Description |
CDH6-sulfo-DM4 induces efficient tumor cell killing in cell PDX models with CDH6 expression.
|
||||
| In Vivo Model | Ovarian cancer CDX model | ||||
| In Vitro Model | Ovarian serous adenocarcinoma | OVCAR-3 cells | CVCL_0465 | ||
References