The GEC-255 small molecule drug project was established earlier than the clinical progress of Amgen and Mirati, and it was the first to apply for an invention patent in China. It was the first echelon KRAS inhibitor pipeline product in China.
Data from adult patients with NSCLC with KRAS G12C mutation who have been treated with GEC255 in Phase I study (NCT05768321) were presented in a poster session at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. The study’s primary endpoint was safety and key secondary endpoints included PK and ORR.
A total of 16 NSCLC patients (15 men, 1 woman, and median age 58) were enrolled in Phase I dose escalation for the first 4 dose cohorts followed by dose escalation in chosen doses. All patients were at clinical stage IIIC-IV and had undergone a median of 1 (0–6) prior systemic treatments, including platinum-based chemotherapy (75%) and immune checkpoint inhibitors (44%).
Tumor response was evaluated in 13 patients. A total of 10 patients (76.9%) had an objective response (complete or partial response) and 12 patients (92.3%) had disease control (objective response or stable disease). In the 600 mg dose group, the ORR was 83.3% and DCR was 100% (n = 6).
Overall no dose-limiting toxicity was observed and MTD was not reached yet up to 800 mg QD. A total of 15 patients had treatment-related adverse events and most AEs were Grade 1 or Grade 2 (93.3%); the most frequent AEs were diarrhea (56.3%), ALT increase (37.5%), rashes (25%), and anemia (25%).
Regarding pharmacokinetics, GEC255 showed a linear increase in AUC exposure and Cmax with increasing doses. Tmax was 2–4 hours in all dosing groups and Ctrough within the 24-hour period was higher than pERK IC90 even in the low-dose group. The half-life of GEC255 in 24 hour period is about 8–9 hours and there was no increase in AUC upon daily dosing for 28 consecutive days.
“GEC255 has shown significant anti-tumor activity in advanced NSCLC patients who have not responded to other treatments. These results justify further investigation of GEC255 in larger clinical trials.”–Expert Opinion.
GEC255, a unique and groundbreaking small molecule characterized by its remarkable selectivity, effective target engagement, and favorable pharmacological properties, has exhibited encouraging efficacy against tumors in patients with advanced non-small cell lung cancer (NSCLC) harboring the KRAS G12C mutation. It has the potential to become the leading inhibitor for KRAS G12C in China