The 2024 Annual Meeting of the European Society of Medical Oncology (ESMO) has be held in Barcelona, Spain, from 13 to 17 September. As one of the largest, most academic and authoritative clinical oncology conferences in the world, the latest results of many important studies will be presented at the conference. Among them, the latest clinical trial data of GB263T GB263T (EGFR/cMET/cMET, TsAb) under Genor Biopharma (Stock code: 6998.HK) was released in the form of a poster on September 14.
As of 31 December 2023, a total of 15 patients had received at least one GB263T treatment. All patients had received previous third-generation EGFR-TKI and platinum-based chemotherapy and the median number of prior lines of systemic therapy was 3.
GB263T has shown promising efficacy at the therapeutic dose range (1,260-1,680 mg).
➢ The objective response rate (ORR) of patients with EGFR-sensitive mutations and resistance to the third-generation TKI treatment at the therapeutic dose range was about 30%;
➢ An apparent benefit was observed in three patients who have developed drugresistant cMET changes after a third-generation TKI treatment.
At the same time, an advantage of safety profile was also demonstrated.
➢ The infusion reaction rate was relatively low and mild;
➢ The incidence rates of nail groove and rash were mild (grade 1/2) with only grade 1 diarrhea;
➢ No MET target-related peripheral edema toxicity has been reported.
GB263T (EGFR/cMET/cMET, TsAb) is the first tri-specific antibody of EGFR/cMET/cMET in the world, targeting EGFR and two different cMET epitopes, so designed to enhance its safety and efficacy profile. With highly differentiated design, GB263T (EGFR/cMET/cMET, TsAb) exhibits multiple mechanisms of action to inhibit primary and secondary EGFR mutations and cMET signaling pathway simultaneously.
In pre-clinical studies, GB263T (EGFR/cMET/cMET, TsAb) effectively thwarted ligand-induced phosphorylation of EGFR and cMET compared to its Amivantamab (JNJ-372) analogue, and demonstrated better dual inhibition of EGFR and cMET signaling pathways. Meanwhile, GB263T (EGFR/cMET/cMET, TsAb) effectively induced the endocytosis of EGFR and cMET, and significantly reduced the protein expression levels of EGFR and cMET. GB263T (EGFR/cMET/cMET, TsAb) played a significant dosage-dependent role in tumor suppression in several different tumor models including EGFR exon 20 insertions, EGFR exon 19 deletions, C797S mutations and various cMET expression abnormalities. In toxicology studies in cynomolgus monkeys, no significant toxic side effects were observed after 4 weeks of observation, even in the highly-dosed group.
