Jacobio Pharma’s investigational combination therapy of glecirasib and sitneprotafib has demonstrated strong early-stage efficacy as a first-line treatment for non-small cell lung cancer (NSCLC), delivering an objective response rate (ORR) of 71 per cent in a Phase I/IIa clinical trial (NCT05288205). The regimen pairs glecirasib, a KRAS G12C inhibitor, with sitneprotafib, an SHP-2 inhibitor, aiming to offer a fully oral, chemotherapy-free option for patients with KRAS G12C-mutated NSCLC.

Jacobio stated that these findings underscore the potential of glecirasib and sitneprotafib to address a significant unmet need in the KRAS G12C-mutant NSCLC population, which represents an estimated 10–13 per cent of all NSCLC cases. The company launched a Phase III trial in 2024 after securing approval from China’s Centre for Drug Evaluation (CDE). If successful, this study could pave the way for the first SHP-2 inhibitor–based combination therapy to receive regulatory approval, marking an important advancement in solid tumour drug development.

Glecirasib has already gained traction in China, having secured approval in May 2025 as a monotherapy for second-line NSCLC, where it demonstrated an ORR of 49.6 per cent in a registrational trial. Moving the drug into the first-line setting through combination therapy could further strengthen Jacobio’s position in the competitive KRAS inhibitor landscape.

KRAS has historically been considered difficult to target due to its structure, leading to its reputation as an “undruggable” protein. However, the approvals of Amgen’s Lumykras (sotorasib) in 2021 and Bristol Myers Squibb’s Krazati (adagrasib) in 2022 have shifted this paradigm. Analysts project that Krazati will reach $281 million in NSCLC sales by 2031, with global revenues across all indications expected to hit $779 million. Lumykras is forecast to peak at $585 million globally in 2031, including $242 million from NSCLC.

The growing commercial interest aligns with broader market expansion, with the NSCLC therapeutics market across the US, EU5, UK, and Canada expected to reach $63.4 billion by 2032. Jacobio’s progress with glecirasib–sitneprotafib positions the company to become a significant contender in this rapidly evolving therapeutic field.