Jacobio's KRAS G12C Combination Therapy Achieves 71% Response Rate in First-Line NSCLC Trial
核心洞察
Jacobio Pharma (搜索)'s combination of glecirasib and sitneprotafib (搜索) demonstrated a 71% objective response rate in 102 previously untreated KRAS G12C (搜索)-mutant NSCLC (搜索) patients during a Phase I/IIa trial.
The oral, chemotherapy-free regimen achieved a median progression-free survival of 12.2 months with manageable safety profile, as only three patients discontinued due to adverse events.
The company initiated a Phase III trial in 2024 following Chinese regulatory approval, potentially positioning this as the first SHP-2 (搜索) inhibitor-based combination therapy to reach market.
Jacobio Pharma (搜索)'s investigational combination therapy of glecirasib and sitneprotafib (搜索) has delivered promising results in a Phase I/IIa clinical trial, achieving a 71% objective response rate (ORR) in 102 previously untreated patients with KRAS G12C (搜索)-mutant non-small cell lung cancer (NSCLC (搜索)). The Beijing-based company's dual-targeting approach combines glecirasib, a KRAS G12C inhibitor, with sitneprotafib, an SHP-2 (搜索) inhibitor, offering a potential fully oral, chemotherapy-free treatment option for this patient population.
Strong Efficacy and Safety Profile
The Phase I/IIa trial (NCT05288205) enrolled 171 patients and demonstrated not only the impressive response rate but also a median progression-free survival of 12.2 months in the first-line NSCLC (搜索) setting. The combination's safety profile proved manageable, with Grade 3 and 4 treatment-emergent adverse events occurring in 46% of patients. The most common adverse events of any grade were anemia and hypertriglyceridemia, affecting 61% and 60% of enrolled patients, respectively. Notably, only three patients discontinued treatment due to adverse events, suggesting good tolerability.
Targeting an "Undruggable" Protein
KRAS has historically been considered one of the most challenging oncology targets due to its structure, which presents few regions where drugs can successfully bind. This led to its reputation as an "undruggable" protein despite being one of the most commonly mutated oncogenes across solid tumor indications. The KRAS G12C (搜索) mutation affects an estimated 10-13% of NSCLC (搜索) patients, representing a significant unmet medical need.
Regulatory Progress and Market Positioning
Jacobio initiated a Phase III trial for the glecirasib-sitneprotafib (搜索) combination in 2024 following approval from China's Centre for Drug Evaluation (CDE). If successful, this study could establish the first SHP-2 (搜索) inhibitor-based combination therapy to gain regulatory approval, potentially opening new therapeutic avenues for solid tumors.
The combination therapy builds on glecirasib's existing success as a monotherapy. The drug secured approval in China in May 2025 for second-line NSCLC (搜索) treatment, where it demonstrated an ORR of 49.6% in a registrational study. Moving glecirasib into the first-line setting through combination therapy could significantly strengthen Jacobio's competitive position.
Competitive Landscape and Market Outlook
The KRAS inhibitor field has evolved rapidly following breakthrough approvals of Amgen's Lumykras (sotorasib) in 2021 and Bristol Myers Squibb (搜索)'s Krazati (adagrasib) in 2022. Analysts project substantial commercial potential for these therapies, with Krazati expected to reach $281 million in NSCLC (搜索) sales by 2031 and $779 million globally across all approved indications. Lumykras is forecast to peak at $585 million globally in 2031, including $242 million from NSCLC.
This growth trajectory aligns with broader market expansion, as the NSCLC (搜索) therapeutics market across the seven major markets (US, France, Germany, Italy, Spain, UK, and Canada) is expected to reach $63.4 billion by 2032. Jacobio's progress with the glecirasib-sitneprotafib (搜索) combination positions the company as a potential significant contender in this rapidly evolving therapeutic landscape.