BAY 2927088, an oral tyrosine kinase inhibitor (TKI), has demonstrated promising efficacy in patients with pretreated HER2-mutant non-small cell lung cancer (NSCLC). Data from cohort D of the phase 1 SOHO-01 trial (NCT05099172), presented at the 2024 IASLC World Conference on Lung Cancer, revealed a significant objective response rate and manageable safety profile, suggesting a potential new treatment option for this patient population.
The SOHO-01 trial is a phase 1/2 global, multicenter study evaluating BAY 2927088. The dose-escalation part has already been completed and reported before, identifying BAY 2927088 at 20 mg twice a day to be the recommended dose. The expansion parts include multiple cohorts evaluating patients with lung cancer with different mutations, subtypes, different prior treatment, and with different tumor characteristics. Cohort D specifically enrolled patients with advanced or metastatic NSCLC harboring HER2 mutations who had received prior chemotherapy but no prior HER2-targeted therapies.
Significant Response Rates Observed
The efficacy analysis included 44 patients, revealing an objective response rate (ORR) of 72.1% (95% CI, 56.3%-84.7%), comprising a 2.3% complete response rate and a 69.8% partial response rate. The stable disease rate was 16.3%, and the progressive disease rate was 11.6%. The disease control rate (DCR) was 83.7% (95% CI, 69.3%-93.2%). The median duration of response (DOR) was 8.7 months (95% CI, 8.7-NE), and the median progression-free survival (PFS) was 7.5 months (95% CI, 4.4-12.2).
Subgroup Analysis Highlights YVMA Insertion Efficacy
Subgroup analysis showed particularly encouraging results in patients with YVMA insertions, the most common HER2 mutation in lung cancer. This subgroup (n=30) achieved an ORR of 90.0% (95% CI, 73.5%-97.9%) and a DCR of 97%. The median DOR was 9.7 months (95% CI, 5.5-NE), and the median PFS was 9.9 months (95% CI, 6.9-NE) in this subgroup. Additionally, patients with brain metastases at baseline (n=8) experienced an ORR of 62.5% (95% CI, 24.5%-91.5%).
Safety and Tolerability
The safety profile of BAY 2927088 was generally manageable. Any-grade treatment-related adverse events (TRAEs) occurred in 95.5% of patients, with 43.2% experiencing grade 3 or higher TRAEs. The most common TRAE was diarrhea (86.4% any grade, 25.0% grade 3 or higher). Other TRAEs included rash (43.2%), paronychia (25.0%), nausea (25.0%), and vomiting (20.5%). Treatment discontinuation due to TRAEs occurred in 6.8% of patients. There was one grade 5 event relating to dyspnea, and no reports of interstitial lung disease or pneumonitis.
Future Directions
According to Xiuning Le, MD, PhD, associate professor at The University of MD Anderson Cancer Center, these data support further investigation of BAY 2927088. A phase 3 trial, SOHO-02 (NCT06452277), has been initiated to compare BAY 2927088 with chemoimmunotherapy in treatment-naive patients with HER2-mutant NSCLC. This randomized, global study aims to confirm the efficacy and safety of BAY 2927088 and potentially establish it as a new standard of care.
"We performed a field subgroup analysis. One that I reported more in detail is the molecular subgroup of patients having YVMA insertions... This is also a population that is harder to treat, so we were excited that we reported a response rate of 90% and disease control rate of 97% in this population," said Dr. Le.
