China
Africa
Explore chapters and articles related to this topic
Antibody-Based Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
At the time of writing, there are nearly 200 bispecific antibodies in clinical trials across several therapeutic areas, and many more at the preclinical stage. There are approximately 70 bsAbs being evaluated in the clinic for the treatment of solid tumors. Examples include ERY974 (GPC3/CD3-targeted), cibisatamab (CEA/CD3-targeted), navicixizumab (DLL4/VEGF-targeted), and amivantamab (EGFR/cMet-targeted). There are also nearly 50 bsAbs being evaluated in the clinic for the treatment of hematological malignancies. Examples include mosunetuzumab (CD20/CD3ε-targeted), flotetuzumab (CD123/CD3-targeted), GEN3013 (CD20/CD3-targeted), and GTB-3550 (CD16/CD33-targeted).
Targeting myeloid cells with bispecific antibodies as novel immunotherapies of cancer
Published in Expert Opinion on Biological Therapy, 2022
Celine A.N. Sewnath, Leonie M. Behrens, Marjolein van Egmond
Amivantamab (JNJ-61186372) is a BsAb targeting both c-MET and endothelial growth factor receptor (EGFR), which are expressed in non-small cell lung cancer (NSCLC). Since it has a fully functional human IgG1 Fc tail, amivantamab can engage macrophages and NK cells via Fcγ receptors. It was shown that amivantamab (at concentrations ranging 0.2–20 nM) induced phagocytosis of the NSCLC tumor cell lines H1975 and HCC-827 (expressing c-MET and EGFR) by human macrophages in vitro [74]. Additionally, 10 µg/ml amivantamab induced trogocytosis – a mechanism whereby ligands or membrane fragments of the tumor cells are transferred to either M1 or M2c macrophages [75]. When macrophages were depleted in an H1975 xenograft model in immunodeficient mice, efficacy of BsAb treatment was reduced, supporting that macrophages play a role in preventing tumor growth after amivantamab therapy [75].
Epidermal growth factor receptor-targeted therapy for the treatment of non-small cell lung cancer: a review of phase II and III trials
Published in Expert Opinion on Emerging Drugs, 2022
Hong-Lian Lu, Guang-Ling Jie, Yi-Long Wu
EGFR exon 20ins are uncommon EGFR mutations, accounting for 1–2% of all NSCLC cases and approximately 10% of EGFR-activating mutations [43]. In NSCLCs, the most frequent insertions are located after Asp770 (28.7%), followed by Val769 (20.5%), Pro772 (17.2%) and His773 (14.0%), in the region encoding amino acids 766–775 [44]. Unlike common EGFR mutations, EGFR exon 20ins have not demonstrated the same sensitivity to EGFR-TKIs. Recently, several agents have been developed to overcome this resistance and have demonstrated promising efficacy. Amivantamab (JNJ-61186372) is a bispecific antibody that targets both EGFR and MET. The CHRYSALIS trial was a phase I study demonstrating the superior efficacy of amivantamab with an objective response rate (ORR) of 40%, a median duration of response (DOR) and PFS of 11.1 months and 8.3 months, respectively, and a low toxic effect [45]. Notably, the clinical benefit was consistent regardless of the position of the exon 20 insertion. Owing to its superior efficacy, amivantamab was the first agent granted approval by the FDA on 21 May 2021 as treatment for patients with EGFR exon 20ins. Further studies of amivantamab are ongoing in patients with EGFR exon 20ins (NCT04077463).
Targeting the EGFR signaling pathway in cancer therapy: What’s new in 2023?
Published in Expert Opinion on Therapeutic Targets, 2023
Sushanta Halder, Soumi Basu, Shobhit P. Lall, Apar K. Ganti, Surinder K. Batra, Parthasarathy Seshacharyulu
Amivantamab: Amivantamab is a monoclonal antibody with dual specificity against EGFR and MET receptors. The US FDA has approved it for the treatment of EGFR exon 20 NSCLC. It is approved based on CHRYSALIS, a non-randomized and open-label clinical trial, which recruited 81 patients with progressive diseases or after platinum-based chemotherapy. The recommended dosage of amivantamab is 1050 mg (once weekly) for patients with body weight <80 kg. For patients with >80 kg, amivantamab will be given at the dose of 1400 mg/weekly once. Side effects of amivantamab include rash, musculoskeletal pain, nausea, vomiting, fatigue, dyspnea, stomatitis, edema, constipation, and infusion-related adverse reactions.