BI 3702025/NBE-002* is a humanized monoclonal antibody that targets receptor tyrosine kinase ROR1 on tumor cells, leading to release of an anthracycline-based toxin that induces DNA damage and cell death.1,2
Clinical trials: A phase 1 clinical trial is currently ongoing to evaluate ROR1 ADC in the treatment of advanced solid tumors.3
Mechanism of action
BI 3702025/NBE-002 is an antibody-drug conjugate (ADC) that consists of a humanized monoclonal antibody directed against the receptor tyrosine kinase ROR1, expressed on the surface of various tumor cells, and is conjugated to the highly-potent anthracycline-based toxin PNU-159682.1
Compared to first-generation ADCs (e.g. with tubulin-targeting toxins), PNU anthracycline-based toxin ADCs are more potent and have shown higher efficacy on tumor cells expressing low levels of antigen target.2 PNU-159682 was 700- to 2,400-fold more potent than nemorubicin and can overcome resistance to vc-MMAE–based conjugates.4
The ROR1 ADC binds to the ROR1-expressing tumor cells in hematologic and solid malignancies. Upon binding of anti-ROR1 ADC to ROR1-expressing tumor cells, ADC is internalized and broken down, releasing the toxin in the tumor cell. PNU toxin exerts its effect by inducing DNA damage and ultimately leads to immunogenic cell death.4
Preclinical data showed that BI 3702025/NBE-002 had significant anti-tumor responses against xenograft models of triple-negative breast cancer, lung adenocarcinoma, ovarian carcinoma, and various sarcomas.1,5 Complete tumor regression in triple-negative breast cancer was found even at the lowest dose in cell models with low ROR1 expression.1,5 Anti-tumor responses were also documented in a fully immune competent setting against an orthotopic breast cancer model, with long-lasting immune protection dependent on CD8 T cells.5
Currently, a study is being done to evaluate the anti-tumor response of BI 3702025/NBE-002 in patients with advanced solid tumors (carcinomas or sarcomas).3
|Trial number||Phase||Treatment||Patient population||Status|
Phase I/II study of BI 3702025/NBE-002, a ROR1 ADC in patients with advanced solid tumors3,5
ADC, antibody-drug conjugate; AE, adverse event; DLT, dose-limiting toxicity; ECOG PS, Eastern Cooperative Oncology Group performance status; MTD, maximum tolerated dose; PFS, progression-free survival; PK; pharmacokinetics; RECIST, Response Evaluation Criteria in Solid Tumors; ROR1, receptor tyrosine kinase-like orphan receptor 1; TNBC, triple-negative breast cancer.
Advanced solid tumors
Active, not recruiting
Beerli RR, et al. American Association for Cancer Research Annual Meeting 2019; Abstract LB-197.
Stefan N, et al. Mol Cancer Therap. 2017;16(5):879-892.
ClinicalTrials.gov. NCT04441099. https://clinicaltrials.gov/ct2/show/NCT04441099 (Accessed: September 2021).
Yu SF, et al. Clin Cancer Res. 2015;21:3298-306.
Tolcher AW, et al. J Clin Oncol. 2021;39:15_suppl: Abstract TPS1108.
*This is an investigational compound and has not been approved. Its safety and efficacy have not been established.
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Page last updated: September 2021
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