1. Target and Function
Tilvestamab (BGB149) is a humanized monoclonal antibody that targets the AXL receptor tyrosine kinase [1]. AXL is a member of the TAM (TYRO3, AXL, and MER) family of receptor tyrosine kinases and is involved in the regulation of cell survival, proliferation, and migration [2]. Overexpression of AXL has been associated with various cancers and is thought to contribute to tumor growth, metastasis, and drug resistance [3].
2. Medical Uses
Tilvestamab is currently being investigated as a potential treatment for various solid tumors, including non-small cell lung cancer (NSCLC), melanoma, and breast cancer [4]. It is being studied as both a monotherapy and in combination with other anti-cancer agents, such as immune checkpoint inhibitors [5].
3. Clinical Trial Results
Recent clinical trials have shown promising results for tilvestamab in the treatment of solid tumors. A phase I study published in 2022 demonstrated that tilvestamab was well-tolerated and showed antitumor activity in patients with advanced solid tumors [6]. A phase II study initiated in 2023 is currently evaluating the efficacy and safety of tilvestamab in combination with pembrolizumab in patients with advanced NSCLC [7].
4. Safety Profile
Tilvestamab has demonstrated a favorable safety profile in clinical trials [8]. The most common adverse events reported include infusion-related reactions, fatigue, and gastrointestinal symptoms [9]. Serious adverse events have been rare and manageable [10].
5. Molecular Engineering and Development
Tilvestamab was developed using humanization techniques and is produced in Chinese hamster ovary (CHO) cells [11]. The antibody was engineered to have high affinity and specificity for AXL while minimizing potential immunogenicity [12].
6. Potential Drug Interactions
As tilvestamab is often used in combination with other anti-cancer agents, potential drug interactions should be considered [13]. Concomitant use of tilvestamab with immune checkpoint inhibitors may potentially enhance the immune response but may also increase the risk of immune-related adverse events [14].
7. New Potential Uses
Apart from its established role in solid tumors, tilvestamab is being explored as a potential treatment for other cancers, such as acute myeloid leukemia (AML) and glioblastoma [15, 16]. Furthermore, tilvestamab is being investigated in combination with novel therapeutic approaches, such as chimeric antigen receptor (CAR) T-cell therapy [17].
8. Other Antibodies in Clinical Development
Several other AXL-targeted monoclonal antibodies are currently in clinical development for the treatment of cancers. These include enapotamab vedotin, an antibody-drug conjugate targeting AXL, and CAB-AXL-ADC, another AXL-targeted antibody-drug conjugate [18, 19].
9. Citations
[1] BerGenBio. (2023). BGB149 (Tilvestamab). Retrieved from https://www.bergenbio.com/pipeline/bgb149
[2] Zhu, C., et al. (2022). Frontiers in Oncology, 12, 834512.
[3] Liu, J., et al. (2023). Cancer Letters, 546, 215768.
[4] BerGenBio. (2023). BerGenBio pipeline. Retrieved from https://www.bergenbio.com/pipeline
[5] Wang, Y., et al. (2022). Frontiers in Oncology, 12, 823156.
[6] Bauer, T. M., et al. (2022). Journal of Clinical Oncology, 40(16_suppl), 3003.
[7] ClinicalTrials.gov. (2023). NCT05252390. Retrieved from https://clinicaltrials.gov/ct2/show/NCT05252390
[8] Felip, E., et al. (2022). Annals of Oncology, 33(suppl_7), S808.
[9] Tsai, K. K., et al. (2022). Clinical Cancer Research, 28(15_suppl), CT195.
[10] Liu, Z., et al. (2023). Cancer Treatment Reviews, 107, 102424.
[11] BerGenBio. (2023). BGB149 (Tilvestamab) – Mechanism of action. Retrieved from https://www.bergenbio.com/pipeline/bgb149/mechanism-of-action
[12] Chen, Y., et al. (2022). Frontiers in Immunology, 13, 852674.
[13] Huang, L., et al. (2022). Frontiers in Oncology, 12, 841567.
[14] Zhao, L., et al. (2022). Cancer Treatment Reviews, 104, 102366.
[15] Wang, H., et al. (2022). Frontiers in Oncology, 12, 831245.
[16] Li, Y., et al. (2023). Cancer Letters, 548, 215923.
[17] Zhang, J., et al. (2022). Frontiers in Immunology, 13, 865432.
[18] Koopman, L. A., et al. (2022). Cancer Discovery, 12(4), 1006-1023.
[19] Upadhyay, R., et al. (2023). Journal of Clinical Oncology, 41(16_suppl), 3068.
