1272P - Updated results from a first-in-human, phase I/II study of GB263T, a novel EGFR/cMET/cMET tri-specific antibody, in patients with advanced EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC)

Background

GB263T, a novel trispecific antibody directed against EGFR and cMET, adopts the design of two humanized VHH antibodies that recognize two different cMET epitopes. Here, we report updated phase I study results of GB263T in patients with advanced EGFRm NSCLC (NCT05332574).

Methods

This multicenter, phase I/II study was conducted to characterize the safety, tolerability, pharmacokinetics and preliminary efficacy of GB263T and establish the recommended Phase 2 dose (RP2D). The phase I portion includes dose escalation and dose expansion. Patients with EGFRm NSCLC with prior EGFR TKI and platinum-based chemotherapy were enrolled. GB263T was given at 140-1680 mg IV weekly for the first two 28-day cycles and biweekly thereafter until disease progression or intolerable toxicity.

Results

As of December 31, 2023, 15 patients were treated. All patients had previously received third-generation EGFR-TKI and platinum-based chemotherapy. The most common treatment-related adverse events (TRAEs) were rash (60.0%), fatigue (40.0%), paronychia (40.0%), and infusion related reaction (33.3%), and all are mild (grade 1/2). Only one patient developed ≥grade 3 TRAE (grade 3 oral mucositis, the only DLT reported at 1680mg, which resolved after symptomatic treatment). AE leading to treatment discontinuation occurred in 1 patient (grade 1 interstitial lung disease (ILD)), who had prior HER3-ADC therapy and already exhibited ILD-like minor image change). No AE leading to death occurred. Among 14 response-evaluable patients, two PRs and 6 SDs were observed. For the patient subset with EGFR sensitive mutations and progressed after third-generation EGFR-TKI treatment, at therapeutic efficacious doses of 1260/1680mg (N=7), confirmed ORR was 28.6% (2/7). Three patients with cMET alterations after third-generation EGFR-TKI demonstrated clear clinical benefit (2 PRs and 1 durable SD), with the longest treatment duration over 12 months (840mg) at data cutoff.

Conclusions

GB263T showed a favorable safety profile with promising efficacy at the therapeutic dose (1260-1680mg) in previously heavily treated patients with EGFRm NSCLC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Genor Biopharma Co. Ltd.

Funding

Genor Biopharma Co. Ltd.

Disclosure

F. Xie, T. Li: Financial Interests, Personal, Full or part-time Employment: Genor Biopharma Co. Ltd. All other authors have declared no conflicts of interest.