Linker Information

General Information of This Linker
Linker ID
LIN0CQOSD
Linker Name
Mc-PEG8-Val-Cit-PABC
Linker Type
Cathepsin-cleavable linker
Antibody-Linker Relation
Cleavable
Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
Rovalpituzumab tesirine [Phase 2]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 5 Activity Data Related to This Level
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).

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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.

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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.

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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.

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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
Click To Hide/Show 11 Activity Data Related to This Level
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
Click To Hide/Show 1 Activity Data Related to This Level
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
Ref 1 Rovalpituzumab Tesirine as a Maintenance Therapy After First-Line Platinum-Based Chemotherapy in Patients With Extensive-Stage-SCLC: Results From the Phase 3 MERU Study. J Thorac Oncol. 2021 Sep;16(9):1570-1581.
Ref 2 Efficacy and Safety of Rovalpituzumab Tesirine in Third-Line and Beyond Patients with DLL3-Expressing, Relapsed/Refractory Small-Cell Lung Cancer: Results From the Phase II TRINITY Study. Clin Cancer Res. 2019 Dec 1;25(23):6958-6966.
Ref 3 A phase I/II study of rovalpituzumab tesirine in delta-like 3-expressing advanced solid tumors. NPJ Precis Oncol. 2021 Aug 5;5(1):74.
Ref 4 Safety, pharmacokinetics, and efficacy of budigalimab with rovalpituzumab tesirine in patients with small cell lung cancer. Cancer Treat Res Commun. 2021;28:100405.
Ref 5 A Phase 1 Study Evaluating Rovalpituzumab Tesirine in Frontline Treatment of Patients With Extensive-Stage SCLC. J Thorac Oncol. 2021 Sep;16(9):1582-1588.
Ref 6 Evaluation of the DLL3-targeting antibody-drug conjugate rovalpituzumab tesirine in preclinical models of neuroblastoma. Cancer Res Commun. 2022 Jul;2(7):616-623.

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