FDA Grants Zongertinib Breakthrough Therapy Designation in HER2-Mutant NSCLC
New data on zongertinib for HER2-positive non–small cell lung cancer will be presented at the IASLC 2024 World Conference on Lung Cancer, shedding light on its potential as a novel treatment option for this patient population.
- Zongertinib (BI 1810631), an investigational oral therapy, was granted breakthrough therapy designation (BTD) from the FDA.
- China’s Center for Drug Evaluation (CDE) also granted a BTD for this agent in adult patients with advanced, unresectable or metastatic non–small cell lung cancer (NSCLC) whose tumors have activating HER2 mutations and who have received prior systemic therapy.
- Data from the Beamion LUNG-1 study (NCT04886804) evaluating zongertinib will be presented at the IASLC 2024 World Conference on Lung Cancer (WCLC) on Monday, September 9, 2024.
The FDA granted zongertinib, a HER2-specific tyrosine kinase inhibitor (TKI), BTD for the treatment of adult patients with advanced, unresectable or metastatic NSCLC harboring HER2 mutations who have received a prior systemic therapy.1
Late-breaking data from the Beamion LUNG-1 trial support this BTD. In this phase 1a/b trial, experts are evaluating the safety and efficacy of zongertinib for the treatment of various solid tumors with changes in the HER2 gene.
The results from this study, including new data from a primary analysis of the first cohort of phase 1b in pretreated patients with HER2-positive NSCLC, will be presented at WCLC.
“Every year, about 40,000 people worldwide are diagnosed with non–small cell lung cancer with a HER2 mutation. While targeted therapy is available for some cancers driven by HER2, people living with HER2-mutated NSCLC have few options,” Carinne Brouillon, head of human pharmaceuticals at Boehringer, said in a press release. “We are proud to be sharing new data evaluating our investigational zongertinib in this hard-to-treat setting. Our strong oncology pipeline underscores our strategic approach in advancing novel targeted treatments and cancer cell-directed therapies that have a potential to transform lives for generations of patients.”
China's CDE also granted zongertinib BTD for this patient population.
illustration of lungs: © yodiyim - stock.adobe.com
About the Phase 1a/b Beamion LUNG-1 Trial
The Beamion LUNG-1 trial is designed to investigate the safety and efficacy of zongertinib in patients with advanced cancer. In the first phase of the study, adults with various HER2-positive solid tumors who have progressed on previous treatment will be enrolled. The goal is to determine the maximum tolerated dose (MTD) of zongertinib.2
In the second phase, patients with NSCLC harboring a specific HER2 mutation will receive zongertinib at the established dose to evaluate its antitumor activity. Zongertinib will be administered orally once or twice daily.
Participants will remain in the study as long as they derive benefit from and can tolerate treatment. Regular monitoring of health status, tumor response, and adverse events will be conducted throughout the study.
The primary end points of the phase 1a are to establish the MTD and determine the number of patients with dose limiting toxicities in the MTD evaluation period. In phase 1b, the primary end point for cohorts 1, 2 and 5 is objective response (OR) as assessed by central independent review. For cohorts 3, 6 and 7, it is OR according to RECIST 1.1 by investigator assessment. For cohort 4, the primary end point is OR according to response assessment in neuro-oncology for brain metastases by central independent review.
Patients must have an advanced, unresectable, or metastatic nonhematologic malignancy with at least 1 measurable lesion according to RECIST 1.1. The ECOG performance status must be 0, 1, or 2, with an ECOG performance status of 2 only for cohorts 6 and 7. A confirmed diagnosis of HER2-positive cancer is required, which can be determined through a biopsy. Patients also must have adequate organ function, including normal or near-normal levels of absolute neutrophil count, hemoglobin, platelets, bilirubin, estimated glomerular filtration rate, aspartate aminotransferase, alanine transaminase, and alkaline phosphatase. Patients must have recovered from any previous therapy-related toxicity to a grade 1 level with certain exceptions. A life expectancy of at least 12 weeks is required.
Additional criteria vary by cohort. For phase 1a, patients must have a documented diagnosis of HER2 aberration. In phase 1b, cohort 1 requires nonsquamous NSCLC with a HER2 tyrosine kinase domain (TKD) mutation and prior systemic therapy. Cohort 2 requires treatment-naive nonsquamous NSCLC with a HER2 TKD mutation. Cohort 3 requires nonsquamous NSCLC with a HER2 mutation outside the TKD or squamous NSCLC with a HER2 TKD mutation, and prior systemic therapy. Cohort 4 requires nonsquamous NSCLC with a HER2 TKD mutation, any prior therapy, and may include patients with brain metastases. Cohort 5 requires nonsquamous NSCLC with a HER2 TKD mutation, prior platinum-based therapy and HER2-targeted antibody-drug conjugate. Cohort 6 requires nonsquamous NSCLC with a HER2 TKD mutation, prior systemic therapy, and no brain metastases or ineligible for immediate local therapy. Cohort 7 is similar to cohort 6 but for patients ineligible for other cohorts.
