Press Release
Sep 09, 2024
(San Diego, Calif.--September 9, 2024, 10:05 a.m.) — Treatment with BAY 2927088 led to rapid, substantial, and durable responses in patients with heavily pretreated HER2-mutant non-small cell lung cancer (NSCLC), according to research presented today at the International Association for the Study of Lung Cancer 2024 World Conference on Lung Cancer.
BAY 2927088 is an oral, reversible tyrosine kinase inhibitor specifically targeting activating HER2 (ERBB2) mutations. Previous studies have demonstrated its manageable safety profile and encouraging preliminary anti-tumor activity in patients with advanced NSCLC harboring HER2 mutations. The drug has received Breakthrough Therapy designation from both the US Food and Drug Administration and the Chinese Center for Drug Evaluation for patients with unresectable or metastatic NSCLC who have previously undergone therapy.
Xiuning Le, M.D., Ph.D., The University of Texas MD Anderson Cancer Center, Houston, TX and National University Hospital, Seoul/KR presented updated results from the expansion cohort of the ongoing Phase I/II SOHO-01 study.
The SOHO-01 study is an ongoing, open-label, multicenter Phase I/II study. The expansion cohort specifically enrolled patients with advanced HER2-mutant NSCLC who had not received HER2-targeted therapy.
Patients with advanced NSCLC harboring a HER2-activating mutation who had experienced disease progression after at least one prior systemic therapy for advanced disease were administered oral BAY 2927088 at a dosage of 20 mg twice daily. The study's objectives were to assess the safety and anti-tumor activity of BAY 2927088, with efficacy evaluated per RECIST v1.1 and safety assessed using MedDRA v27.0.
Dr. Le and her colleague enrolled a total of 44 patients, who had a median age of 62 years-- 63.6% were female, 70.5% had never smoked, and 54.5% had received two or more lines of therapy. The researchers followed up on the patients for 10.9 months.
Of the 43 patients evaluable for efficacy, Dr. Le reported a confirmed objective response rate of 72.1% (n=31; 95% CI 56.3, 84.7), including one complete response (2.3%). The median duration of response and progression-free survival were 8.7 months (95% CI 4.5, not estimable) and 7.5 months (95% CI 4.4, 12.2), respectively.
In a subgroup analysis, patients with tumors harboring HER2 Y772_A775dup (YVMA) exon 20 insertion mutations had an objective response rate of 90.0%. Among the eight patients with previously treated and asymptomatic brain metastases, the objective response rate was 62.5%.
Dr. Le reported that the safety profile of BAY 2927088 was manageable and consistent with previous reports, reinforcing its potential as a promising therapy for patients with advanced NSCLC harboring HER2 mutations.
“These data from the SOHO-01 study underscore the potential of BAY 2927088 as a treatment for patients with advanced NSCLC harboring HER2 mutations,” said Dr. Le. “The drug demonstrated substantial and durable responses in a heavily pretreated patient population, with a manageable safety profile. These findings support the continued investigation of BAY 2927088 in this patient group, especially in light of its recent Breakthrough Therapy designation by the FDA.”
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About the IASLC:
The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated solely to the study of lung cancer and other thoracic malignancies. Founded in 1974, the association's membership includes more than 10,000 lung cancer specialists across all disciplines in over 100 countries, forming a global network working together to conquer lung and thoracic cancers worldwide. The association also publishes the Journal of Thoracic Oncology, the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis, and treatment of all thoracic malignancies. Visit www.iaslc.org for more information.
About the WCLC:
The World Conference on Lung Cancer (WCLC) is the world’s largest meeting dedicated to lung cancer and other thoracic malignancies, attracting nearly 7,000 researchers, physicians and specialists from more than 100 countries. The goal is to increase awareness, collaboration and understanding of lung cancer, and to help participants implement the latest developments across the globe. The conference will cover a wide range of disciplines and unveil several research studies and clinical trial results. For more information, visit https://wclc2024.iaslc.org.
Abstract Control Number:
2193
Abstract Type:
Late-Breaking Abstract
Track:
12. Metastatic Non-small Cell Lung Cancer - Targeted Therapy
Title:
Safety and Efficacy of BAY 2927088 In Patients with HER2-Mutant NSCLC: Expansion Cohort from the Phase I/II SOHO-01 Study
Sections:
Introduction:
BAY 2927088 is an oral, reversible tyrosine kinase inhibitor that potently inhibits activating
HER2 ERBB2 m)mutations and has shown manageable safety and encouraging preliminary anti-tumor activity in patients with advanced NSCLC harboring HER2 mutations (Girard et al. ASCO 2024). The US FDA and Chinese Center for Drug Evaluation have granted Breakthrough Therapy designation to BAY 2927088 for patients with unresectable or metastatic NSCLC with activating HER2 mutations who have already received therapy. Here we report updated results of BAY 2927088 from an expansion cohort of patients with HER2 -mutant NSCLC naïve to HER2 -targeted therapy enrolled in the SOHO-01 study
(NCT05099172).
Methods:
SOHO-01 is an ongoing, open-label, multicenter Phase I/II study. Patients with advanced NSCLC harboring a HER2 -activating mutation with disease progression after ≥1 systemic therapies for advanced disease and naïve to HER2 targeted therapy received oral BAY 2927088 20 mg twice daily. Study objectives included safety and anti-tumor activity (RECIST v1.1). Safety was assessed using MedDRA v27.0.
Results:
Forty-four patients were treated, with a median follow-up of 10.9 months. Median age was 62 years, 63.6% were female, 70.5% had never smoked, and 54.5% had received ≥2 lines of therapy. Forty-three patients were evaluable for efficacy, with a confirmed objective response rate (ORR) of 72.1% (n=31; 95% CI 56.3, 84.7) including 1 complete response (2.3%). Median duration of response and progression-free survival were 8.7 months (95% CI 4.5, not estimable) and 7.5 months (95% CI 4.4, 12.2), respectively. Selected subgroup ORRs are shown in table . Thirty patients had tumors harboring HER2 Y772_A775dup (YVMA) exon 20 insertion mutations, and the ORR was 90.0%. Eight patients had previously treated and asymptomatic brain metastases at baseline, and the ORR was 62.5%. Treatment-related adverse events (TRAEs) were reported in 95.5% of patients, with grade 3 TRAEs reported in 40.9%; there were no grade 4 TRAEs and one grade 5 event (dyspnea). Diarrhea was the most common TRAE (86.4%, 25.0% grade 3), followed by rash (43.2% grade 1 or 2) and paronychia (25.0% grade 1 or 2). Three patients (6.8%) discontinued due to TRAEs.
Conclusions:
Treatment with BAY 2927088 led to rapid, substantial, and durable responses in patients with heavily pretreated HER2 -mutant NSCLC. The safety profile of BAY 2927088 was manageable and consistent with previous reports. These data support the ongoing investigation of BAY 2927088 in patients with advanced NSCLC harboring HER2 mutations.$$graphic_{98F99C1E-0C65-43C1-B482-A477F9D03F48}$$
LBA Reason:
If accepted, this abstract will include data that have potential implications for the treatment of patients with advanced NSCLC harboring HER2-activating mutations, including key safety and efficacy data (overall response rate, duration of response, and progression-free survival) from a cohort of patients naive to HER2-targeted antibody-drug conjugates. This report follows a recent Breakthrough Therapy designation from the FDA for BAY 2927088 in patients with HER2-mutant NSCLC.
Breakthrough Therapy designation is a process designed to expedite the development and review of investigational drugs that have potential to provide substantial improvement over available therapy in areas of high unmet need. Data cut-off was planned for July 15.
LBA Type of Analysis and Data:
Safety analyses will include the evaluation of treatment-emergent adverse events (TEAEs), serious TEAEs, treatment-related TEAEs, and dose modifications due to TEAEs. Efficacy analyses will include investigator assessment of the overall response rate, duration of response, and progression-free survival per RECIST v1.1.
Presenter:
Xiuning Le, MD Anderson Cancer Center, United States
National University Hospital, Seoul/KR
Presenter:
Xiuning Le, MD Anderson Cancer Center, United States