Jacobio's NSCLC combination demonstrates 71% ORR in Phase I/IIa study

Jacobio Pharma's experimental combination therapy of glecirasib and sitneprotafib has demonstrated encouraging results in an early-stage study for previously untreated non-small cell lung cancer (NSCLC) patients. Conducted as a Phase I/IIa trial (NCT05288205), the regimen combines glecirasib, a KRAS G12C inhibitor, with sitneprotafib, an SHP-2 inhibitor, and achieved a remarkable objective response rate (ORR) of 71% among 102 participants.

Beyond the ORR, the combination showed a median progression-free survival (PFS) of 12.2 months in the first-line NSCLC context. Treatment-related Grade 3 and 4 adverse events occurred in 46% of patients. The most frequent side effects of any severity were anemia (61%) and hypertriglyceridemia (60%) among the 171 patients enrolled. Notably, only three participants discontinued therapy due to adverse events.

Headquartered in Beijing, Jacobio emphasizes that the therapy could provide a fully oral, chemotherapy-free option for patients with KRAS G12C-mutated NSCLC, a mutation present in an estimated 1013% of NSCLC cases. In 2024, the company initiated a Phase III trial in China for frontline treatment of KRAS G12C-mutant NSCLC following approval from Chinas Centre for Drug Evaluation (CDE).

If successful, this combination could become the first therapy including an SHP-2 inhibitor to gain regulatory approval, creating a new treatment avenue for solid tumors. It would also advance glecirasib into the first-line setting, after its May 2025 approval as a monotherapy for second-line NSCLC in China, where it showed an ORR of 49.6% in a registrational study.

KRAS has long been recognized as a frequently mutated oncogene in solid tumors but remains a challenging target due to its structural features, which limit drug binding and previously led to it being labeled undruggable. Despite these challenges, two KRAS G12C-targeted drugs have gained FDA approval for NSCLC: Amgens Lumykras (sotorasib) in 2021 and Bristol Myers Squibbs Mirati Therapeutics Krazati (adagrasib) in 2022.

Market forecasts predict that Krazati will reach $281 million in NSCLC sales by 2031 and $779 million across all approved indications, including colorectal cancer. Lumykras is expected to achieve global sales of $585 million by the same year, with $242 million attributed to NSCLC. These projections come as the NSCLC market is anticipated to reach $63.4 billion across the seven major markets (US, France, Germany, Italy, Spain, UK, and Canada) by 2032.

Jacobios recent Phase I/IIa data reinforce the potential of its glecirasib-sitneprotafib combination as a potent, orally administered, chemotherapy-free treatment option for KRAS G12C-mutant NSCLC.

Author: Sophia Brooks