Groundbreaking Advances in Lung Cancer Treatment: New Combo Therapy Shows Promise

Introduction

Jacobio Pharma recently presented compelling data from their ongoing research on a new combination therapy for non-small cell lung cancer (NSCLC) at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. The new therapy combines a KRAS G12C inhibitor, glecirasib, with an SHP2 inhibitor, JAB-3312, showing significant promise for patients with the KRAS G12C mutation.

Study Overview

As of April 7, 2024, the phase II trial enrolled 194 patients, including 102 frontline NSCLC patients. The study focused on evaluating the efficacy of combining glecirasib and JAB-3312. Researchers followed the participants for a median duration of 10.1 months, highlighting the trial's robust design and thoroughness.

Key Findings

The data was presented in an oral abstract session by Professor Jun Zhao of Beijing Cancer Hospital. Among the 102 frontline NSCLC patients, seven different dose groups were tested. Key metrics included a confirmed objective response rate (cORR) of 64.7%, a disease control rate (DCR) of 93.1%, and a median progression-free survival (mPFS) of 12.2 months.

Optimal Dosage

Researchers identified the optimal dose as glecirasib at 800mg daily and JAB-3312 at 2mg daily, administered one week on andone week off. This dosing regimen achieved a cORR of 77.4% and saw 54.8% of patients experiencing a significant tumor reduction by more than 50%. The median progression-free survival for this group is still being determined.

Safety Data

The safety profile was carefully monitored, revealing that 43.8% of the 194 patients experienced grade 3 or 4 treatment-related adverse events (TRAEs). Encouragingly, there were no treatment-related deaths. Common adverse events included anemia and hypertriglyceridemia. Safety outcomes in frontline NSCLC were consistent with the broader patient population, indicating that the treatment's safety profile is manageable.

Expert Commentary

Professor Jie Wang of Beijing Cancer Hospital emphasized the promising safety and efficacy data. He noted that if this combination therapy proves superior to current standard treatments (chemotherapy and immunotherapy) in future trials, it could potentially minimize chemotherapy or immunotherapy's side effects.

Future Directions

The combination therapy is now entering a Phase III clinical trial in China for frontline NSCLC patients with KRAS G12C mutation. Dr. Andrea Gillam-Wang, Chief Medical Officer and Global Head of R&D at Jacobio, highlighted the company's focus on patient needs and expressed optimism about this novel treatment potentially replacing standard care regimens.

Ongoing Trials

Beyond the NSCLC study, glecirasib is under investigation in various Phase I/II trials worldwide, targeting advanced solid tumors with the KRAS G12C mutation. These trials include combinations with SHP2 inhibitor JAB-3312 and cetuximab for colorectal cancer, demonstrating broad applicability.

Regulatory Milestones

In a significant milestone, the new drug application (NDA) for glecirasib as a monotherapy for second-line NSCLC was granted Priority Review by China's Center for Drug Evaluation (CDE) on May 21, 2024. This recognition underscores the potential impact of glecirasib on patient care.

Conclusion

The combination therapy of glecirasib and JAB-3312 presents a promising advancement in treating NSCLC. With ongoing trials and regulatory progress, there is hope for a shift towards more tolerable and effective treatments for patients with the KRAS G12C mutation.