In a phase Ia/Ib study (Beamion LUNG-1) reported in the Journal of Clinical Oncology, Heymach et al evaluated the safety profile and activity of zongertinib in patients with HER2-altered solid tumors. Zongertinib is a novel HER2-selective tyrosine kinase inhibitor (TKI) that spares EGFR, thereby helping to reduce EGFR toxicities associated with some TKIs.
The study assessed the efficacy of zongertinib given twice daily at 15 to 150 mg or once daily at 60 to 360 mg in 105 previously treated patients with various solid tumors, including non–small cell lung cancer (NSCLC). The primary endpoints were maximum tolerated dose (MTD) and dose-limiting toxicities; a secondary endpoint was tumor response.
Key Findings
Two dose-limiting toxicities (grade 3 diarrhea and grade 3 thrombocytopenia) were observed during the MTD evaluation period. MTD was not reached, and the recommended doses for the expansion phase were 120 mg once daily and 240 mg once daily.
Treatment-related adverse events of any grade occurred in 82% of patients (10% grade ≥ 3), most commonly diarrhea (50%, 1% grade ≥ 3), rash (16%, 2% grade ≥ 3), anemia (10%, 0% grade ≥ 3), decreased appetite (10%, 1% grade ≥ 3), and increased alanine transaminase (10%, 4% grade ≥ 3).
For all doses and all tumors, the investigator-assessed objective response rate was 30% (95% confidence interval [CI] = 23%–40%) and median duration of response was 12.7 months (95% CI = 6.9 months to not reached). In 54 patients with NSCLC, the objective response rate was 35% (95% CI = 24%–49%); among 24 of these patients with the A775_G776insYVMA mutation, the objective response rate was 38%. In patients with NSCLC receiving once-daily zongertinib, median progression-free survival was 17.2 months (95% CI = 8.3 months to not reached).
Responses were also observed among 48 patients who had received previous HER2-directed therapy (objective response rate = 28%) and among 25 who had received previous antibody-drug conjugate treatment (objective response = 32%).
The investigators concluded: “Zongertinib had a manageable safety profile and demonstrated preliminary antitumor activity in patients with HER2-altered tumors, including those with HER2-mutant NSCLC.”
John V. Heymach, MD, PhD, of the Department of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosures: The study was supported by Boehringer Ingelheim. For full disclosures of all study authors, visit ascopubs.org.
