Safety and efficacy of GFH276 monotherapy in previously treated RAS-mutated advanced solid tumors

GFH276

Paziente / Popolazione Intervento / Esposizione Confronto Esito

In patients with previously treated RAS-mutated advanced solid tumours who received 40-160 mg in dose escalation, GFH276 monotherapy produced an objective response rate of 36% and a disease control rate of 94%, with no dose-limiting toxicities.

N

98pazienti

Disegno

First-in-human, single-arm dose-escalation (accelerated titration followed by Bayesian Optimal Interval design) and expansion study of oral GFH276 monotherapy in patients with RAS-mutated advanced solid tumours refractory to or intolerant of standard therapy, including those who failed KRAS G12C/D inhibitors (NCT07198321).

Esito

Not stated in the abstract. The study reports safety, pharmacokinetics and antitumour activity (objective response rate and disease control rate).

RisultatoOf 98 patients treated in dose escalation, 80 received 40-160 mg. In these 40-160 mg cohorts, objective response rate was 36% (29/80) and disease control rate 94% (75/80). In pancreatic cancer, ORR 38% (23/61) and DCR 93% (56/61). In NSCLC, ORR 38% (6/16) and DCR 81% (13/16). Median follow-up 9 weeks (range 1-42). Partial responses were seen with KRAS G12A/D/R/V, KRAS G13E, KRAS Q61H and NRAS G12D. No dose-limiting toxicities were observed. In the 40-160 mg cohorts, treatment-related AEs occurred in 98.8%, grade 3 in 27.5%, with no grade 4 or 5 events. The most common were rash 83.8% (grade 3 7.5%), anaemia 63.8% (grade 3 3.8%), stomatitis 55.0% (grade 3 2.5%), diarrhoea 48.8% (grade 3 3.8%) and hypoalbuminaemia 45.0% (no grade 3). Dose reductions, interruptions and permanent discontinuations due to treatment-related AEs occurred in 17.5%, 22.5% and 1.3%.

Ma Y, Zhao H, Shi S, et al. Presented at ESMO Congress 2026, abstract LBA33, 25 October. Not yet published.

Discussione e critica

These preliminary dose-escalation data show responses in 36% of the 80 patients treated at 40-160 mg, across several KRAS and NRAS variants, with grade 3 treatment-related AEs in 27.5% and no grade 4 or 5 events in that group. Median follow-up is only 9 weeks, so the abstract cannot show how long responses last or any effect on progression-free or overall survival, and it does not say whether responses were confirmed. The study is single-arm with no comparator and names no primary endpoint. It gives no efficacy or safety figures for doses outside 40-160 mg, and no response rates by mutation subtype or by prior KRAS inhibitor exposure.