Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0ULCEQ
|
|||||
|---|---|---|---|---|---|---|
| ADC Name |
Rovalpituzumab tesirine
|
|||||
| Synonyms |
P256HB60FF; SC-0002; SC0001-SCX; SC0001SCX; SC16LD6.5; Rova-T
Click to Show/Hide
|
|||||
| Organization |
AbbVie, Inc.
|
|||||
| Drug Status |
Phase 2
|
|||||
| Indication |
In total 7 Indication(s)
Small cell lung cancer [ICD11:2C25]
Phase 2
Glioblastoma [ICD11:2A00]
Terminated in phase 2
Islet cell carcinoma [ICD11:2C10]
Terminated in phase 2
Melanoma [ICD11:2C30]
Terminated in phase 2
Prostate cancer [ICD11:2C82]
Terminated in phase 2
Solid tumors [ICD11:2A00-2A0Z|2B50-2F9Z]
Terminated in phase 2
Medullary thyroid carcinoma [ICD11:2D10]
Terminated in phase 1
|
|||||
| Drug-to-Antibody Ratio |
2
|
|||||
| Structure |
|
|||||
| Antibody Name |
Rovalpituzumab
|
Antibody Info | ||||
| Antigen Name |
Delta-like protein 3 (DLL3)
|
Antigen Info | ||||
| Payload Name |
SG3199
|
Payload Info | ||||
| Therapeutic Target |
Human Deoxyribonucleic acid (hDNA)
|
Target Info | ||||
| Linker Name |
Mc-PEG8-Val-Cit-PABC
|
Linker Info | ||||
| Conjugate Type |
Random conjugation through reduced inter-chain cysteines.
|
|||||
| Combination Type |
Tesirine
|
|||||
| Special Approval(s) |
Orphan drug(FDA)
|
|||||
| Puchem SID | ||||||
| Drugbank ID | ||||||
| ChEBI ID | ||||||
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Discovered Using Patient-derived Xenograft Model
Discovered Using Cell Line-derived Xenograft Model
| Standard Type | Value | Units | Cell Line | Disease Model |
|---|---|---|---|---|
| Tumor Growth Inhibition value (TGI) |
≈ 99
|
%
|
COG-N-415 cells
|
Neuroblastoma
|
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] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
10.00%
|
|||
| Patients Enrolled |
Extensive-stage small-cell lung cancer (ES-SCLC) who had completed four cycles of front-line platinum-based chemotherapy (cisplatin or carboplatin with etoposide or irinotecan) at least 3 weeks but not more than 9 weeks before randomization and had stable disease, PR, or CR per RECIST v.1.1.
|
||||
| Administration Dosage |
0.30 mg/kg intravenous Rova-T on day 1 of each 6-week cycle, omitting every third cycle.
|
||||
| Related Clinical Trial | |||||
| NCT Number | NCT03033511 | Clinical Status | Phase 3 | ||
| Clinical Description | A randomized, double-blind, placebo-controlled phase 3 study of rovalpituzumab tesirine as maintenance therapy following first-line platinum-based chemotherapy in subjects with extensive stage small cell lung cancer (MERU). | ||||
| Primary Endpoint |
Median age of all randomized patients (N=748) was 64 years; 78.00% had TNM stage IV disease. At futility analysis of the subset with DLL3-high tumors, the hazard ratio for OS was 1.07 (95% confidence interval: 0.84-1.36) favoring the placebo arm,with median OS of 8.50 and 9.80 months in the Rova-T and placebo arms,respectively; futility criteria were met. Rova-T significantly improved PFS versus placebo by investigator assessment (4.00 versus 1.40 mo,hazard ratio=0.48, p < 0.001).
Click to Show/Hide
|
||||
| Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
12.40% (all)
14.30% (DLL3-high) 13.20% (DLL3-positive) |
|||
| Patients Enrolled |
Advanced stage DLL3-positive small-cell lung cancer (SCLC).
|
||||
| Administration Dosage |
0.30 mg/kg Rova-T intravenously infused over 30 minutes once every 6 weeks for two cycles.
|
||||
| Related Clinical Trial | |||||
| NCT Number | NCT02674568 | Clinical Status | Phase 2 | ||
| Clinical Description | An Open-label, Single-Arm, Phase 2 Study Evaluating the Efficacy, Safety and Pharmacokinetics of Rovalpituzumab Tesirine (SC16LD6.5) for Third-line and Later Treatment of Subjects With Relapsed or Refractory Delta-Like Protein 3-Expressing Small Cell Lung Cancer (TRINITY). | ||||
| Primary Endpoint |
OrR was 12.40%, 14.30%, and 13.20% in all, DLL3-high, and DLL3-positive patients,respectively. Median OS was 5.60 months in all patients and 5.70 months in DLL3-high patients.
|
||||
| Experiment 3 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
17.14% (In pooled patients with NEC/NET expressing a high level of DLL 3% (50% DLL3-positive tumor cells))
8.82% (In those with NEC/NET expressing a low level of DLL 3% (1-49% DLL3-positive tumor cells)) |
|||
| Patients Enrolled |
101 with NEC/NET (large-cell NEC, gastroenteropancreatic NEC, neuroendocrine prostate cancer, and other NEC/NET) and 99 with other solid tumors (melanoma, medullary thyroid cancer [MTC], glioblastoma, and other).
|
||||
| Administration Dosage |
The recommended phase II dose (RP2D) was 0.30 mg/kg every 6 weeks (q6w) for two cycles.
|
||||
| Related Clinical Trial | |||||
| NCT Number | NCT02709889 | Clinical Status | Phase 1/2 | ||
| Clinical Description | An open-label study of rovalpituzumab tesirine in subjects with delta-like protein 3-expressing advanced solid tumors. | ||||
| Primary Endpoint |
The recommended phase II dose (RP2D) was 0.30 mg/kg every 6 weeks (q6w) for two cycles. At the RP2D, grade 3/4 adverse events included anemia (17.00%), thrombocytopenia (15.00%), and elevated aspartate aminotransferase (8.00%). Responses were confirmed in 15/145 patients (10.34%) treated at 0.30 mg/kg, including 9/69 patients (13.04%) with NEC/NET. Rova-T at 0.30 mg/kg q6w had manageable toxicity, with antitumor activity observed in patients with NEC/NET, melanoma, MTC, and glioblastoma.
Click to Show/Hide
|
||||
| Other Endpoint |
In pooled patients with NEC/NET expressing a high level of DLL3 (50% DLL3-positive tumor cells), the ORR was 17.14% (6/35) and 34.29% (12/35) had a BOR (all PRs). In those with NEC/NET expressing a low level of DLL3 (1-49% DLL3-positive tumor cells), the ORR was 8.82% (3/34) and the BOR rate was 14.70% (5/34) (all PRs). The median PFS values for pooled patients with NEC/NET expressing high and low levels of DLL3 were 4.30 months (95% CI, 2.7-6.1) and 3.30 months (95% CI, 2.40-4.80), respectively. The median OS values for patients expressing high and low levels of DLL3 were 7.40 months (95% CI, 5.60-13.10) and 7.10 months (95% CI, 4.30-9.90), respectively.
Click to Show/Hide
|
||||
| Experiment 4 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
34.50% (All evaluable patients)
31.60% (DLL3 score 75%) 50.00% (PD-L1 positive tumor cells) 50.00% (PD-L1 positive inflammatory cells with an intensity of 2+) |
|||
| Patients Enrolled |
Progressive small-cell lung cancer (SCLC) who had previously been treated with at least one prior line of platinum-containing chemotherapy were enrolled if they were naive to PD-1/PD-L1targeting agents, had ECOG performance status 0-1, measurable disease per RECIST v1.1 or disease evaluable by tumor antigen assessment, and adequate bone marrow, cardiac, hepatic, and renal functions.
Click to Show/Hide
|
||||
| Administration Dosage |
Budigalimab 375 mg via intravenous infusion every 3 weeks and Rova-T was administered as a dose of 0.30 mg/kg intravenously, on day 1 of the first and third 3-week cycle.
|
||||
| Related Clinical Trial | |||||
| NCT Number | NCT03000257 | Clinical Status | Phase 1 | ||
| Clinical Description | A multicenter, phase 1, open-label, dose-escalation study of ABBV-181 as monotherapy and in combination with another anti-cancer therapy in subjects with advanced solid tumors. | ||||
| Primary Endpoint |
In patients with DLL3 score 75.00% (n = 19) the response rate was similar to the total evaluable population, with an ORR of 21.10% (90% CI: 7.50-41.90).
|
||||
| Experiment 5 Reporting the Activity Date of This ADC | [5] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
50.00% (all)
63.00% (0.1 mg/kg Rova-T) 33.00% (0.2 mg/kg Rova-T) |
|||
| Patients Enrolled |
Extensive-stage small-cell lung cancer (ES SCLC), with a response of stable disease or better after the prestudy CE cycle per the Response Evaluation Criteria in Solid Tumors version 1.1, Eastern Cooperative Oncology Group performance status of 0 to 1, and absent or treated central nervous system metastases.
|
||||
| Administration Dosage |
Rova-T monotherapy (0.30 mg/kg, every 6 [q6] wk 2; cohort 1; n = 4); Rova-T induction (0.30 mg/kg, q6 wk 2) followed by CE every 21 days (q21) 4 (cohort 2; n = 5); Rova-T (0.10 or 0.20 mg/kg, q6 wk 2) overlapping with CE q21 4 (cohort 3; n = 14); and Rova-T maintenance (0.30 mg/kg, q6 wk 2) after CE q21 4 (cohort 4; n = 3).
|
||||
| Related Clinical Trial | |||||
| NCT Number | NCT02819999 | Clinical Status | Phase 1 | ||
| Clinical Description | A study of rovalpituzumab tesirine (SC16LD6.5) in the frontline treatment of patients with extensive stage small cell lung cancer. | ||||
| Primary Endpoint |
Median age was 66 years, and 73.00% had Eastern Cooperative Oncology Group performance status of 1. In cohort 3,seven patients (50%) had confirmed objective responses,with a median progression-free survival of 5.20 months and median overall survival of 10.30 months.
|
||||
Discovered Using Patient-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 16.00% (Day 9) | High DLL3 expression (DLL3+++) | ||
| Method Description |
The inhibitory activity of Rova-T against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.1 mg/kg.
|
||||
| In Vivo Model | Neuroblastoma PDX model (PDX: COG-N-415x) | ||||
| Experiment 2 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 30.00% (Day 9) | High DLL3 expression (DLL3+++) | ||
| Method Description |
The inhibitory activity of Rova-T against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.3 mg/kg.
|
||||
| In Vivo Model | Neuroblastoma PDX model (PDX: COG-N-415x) | ||||
| Experiment 3 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 33.00% (Day 28) | High DLL3 expression (DLL3+++) | ||
| Method Description |
The inhibitory activity of Rova-T against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 1 mg/kg weekly x 1.
|
||||
| In Vivo Model | Neuroblastoma PDX model (PDX: COG-N-415x) | ||||
| Experiment 4 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 40.74% (Day 9) | High DLL3 expression (DLL3+++) | ||
| Method Description |
The inhibitory activity of Rova-T against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.1 mg/kg.
|
||||
| In Vivo Model | Neuroblastoma PDX model (PDX: COG-N-452x) | ||||
| Experiment 5 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 50.90% (Day 10) | High DLL3 expression (DLL3+++) | ||
| Method Description |
The inhibitory activity of Rova-T against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.1 mg/kg.
|
||||
| In Vivo Model | Neuroblastoma PDX model (PDX: COG-N-519x) | ||||
| Experiment 6 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 59.81% (Day 9) | High DLL3 expression (DLL3+++) | ||
| Method Description |
The inhibitory activity of Rova-T against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.3 mg/kg.
|
||||
| In Vivo Model | Neuroblastoma PDX model (PDX: COG-N-452x) | ||||
| Experiment 7 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 73.87% (Day 10) | High DLL3 expression (DLL3+++) | ||
| Method Description |
The inhibitory activity of Rova-T against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.3 mg/kg.
|
||||
| In Vivo Model | Neuroblastoma PDX model (PDX: COG-N-519x) | ||||
| Experiment 8 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 78.50% (Day 9) | High DLL3 expression (DLL3+++) | ||
| Method Description |
The inhibitory activity of Rova-T against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.6 mg/kg.
|
||||
| In Vivo Model | Neuroblastoma PDX model (PDX: COG-N-452x) | ||||
| Experiment 9 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 83.00% (Day 9) | High DLL3 expression (DLL3+++) | ||
| Method Description |
The inhibitory activity of Rova-T against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.6 mg/kg.
|
||||
| In Vivo Model | Neuroblastoma PDX model (PDX: COG-N-415x) | ||||
| Experiment 10 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 94.14% (Day 10) | High DLL3 expression (DLL3+++) | ||
| Method Description |
The inhibitory activity of Rova-T against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.6 mg/kg.
|
||||
| In Vivo Model | Neuroblastoma PDX model (PDX: COG-N-519x) | ||||
| Experiment 11 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 94.83% (Day 10) | High DLL3 expression (DLL3+++) | ||
| Method Description |
The inhibitory activity of Rova-T against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.6 mg/kg.
|
||||
| In Vivo Model | Neuroblastoma PDX model | ||||
Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 99.00% (Day 28) | High DLL3 expression (DLL3+++) | ||
| Method Description |
The inhibitory activity of Rova-T against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 1 mg/kg weekly x 3.
|
||||
| In Vivo Model | COG-N-415 neuroblastoma model | ||||
| In Vitro Model | Neuroblastoma | COG-N-415 cells | CVCL_AQ23 | ||
References
If you find any error in data or bug in web service, please kindly report it to Dr. Shen et al.