Boehringer Ingelheim unveiled new data from its top oncology prospect zongertinib, further backing the drug’s prowess in previously treated patients with advanced non-small cell lung cancer (NSCLC) who have the relatively rare human epidermal growth factor receptor 2 (HER2)- mutations within the tyrosine kinase domain (TKD).
At this year’s American Association for Cancer Research (AACR) Annual Meeting in Chicago, the German drugmaker added durability and progression free survival (PFS) results to the breadth of data linked to zongertinib from the company’s formerly announced phase 1b Beamion LUNG-1 trial.
In the study, Boehringer divided patients across five cohorts, but cohort 1, made up of 75 previously treated patients, took the orally administrated tyrosine kinase inhibitor (TKI) zongertinib 120 mg once a day and was powered as the primary analysis cohort.
Here, Boehringer saw a median duration of response of 14.1 months and helped patients live longer without their disease getting worse for a median of 12.4 months, indicating the potential for the med to “impact clinical practice,” Boehringer said in a press release.
The results, which were published in The New England Journal of Medicine, add to zogertinib’s known spread of clinical results. That includes an objective response rate of 71%, a complete response rate of 7% (64% partial response) and a disease control rate of 96%, showing “nearly all patients benefiting from zongertinib,” Boehringer’s global head of oncology, SVP Itziar Canamasas, Ph.D., summed up in an interview with Fierce.
All told, the data go to show that zongertinib could represent a “breakthrough” for the patient population, which typically experiences “quite aggressive” disease, Canamasas said. Beyond efficacy, no drug-related deaths, instances of interstitial lung disease or cardiotoxicity were reported in Lung-1, making for a risk/benefit profile that Boehringer believes is “unparalleled.”
Zongertinib is up for an FDA decision in the third quarter of this year. If approved, the drug would be the first oral, targeted treatment option in the disease space, reflecting a key chemo-free option. It’s a “true precision oncology agent that was beautifully designed,” Canamasas mused, meant to inhibit only HER2 and not target EGFR, another more common NSCLC mutation.
HER2 mutations are typically associated with breast and gastric cancers but make up around 2% of lung cancer patients, typically in those who never smoked.
“Until recently, there were no effective targeted therapies for HER2-mutated NSCLC,” coordinating trial investigator John V. Heymach, M.D., Ph.D., explained in the AACR release on the data. “This potentially practice-changing approval of zongertinib would provide access to a highly efficacious treatment option with a manageable safety profile and would be the first oral therapy and only tyrosine kinase inhibitor approved for patients with HER2-mutated NSCLC.”
Lung cancer, in all its forms, is the second most commonly diagnosed cancer in the U.S., with about 250,000 diagnoses each year. For patients with metastatic NSCLC, prognosis is poor, with only around 8% living beyond five years after diagnosis.
AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate Enhertu is currently the only drug cleared to treat NSCLC patients with tumors that have an activating HER2 mutation, leaving plenty of room for other treatment options. Enhertu carries risks of “significant” side effects and isn’t effective in all patients, Heymach explained in the AACR release on the data, as they look ahead for their drug's launch angle.
Enhertu nabbed that accelerated FDA approval as the first HER2-directed med for patients with previously treated HER2-mutant metastatic NSCLC, back in 2022.
The data for that green light came from the Destiny-Lung02 phase 2 test. This trial, made from an interim efficacy analysis in a prespecified patient cohort, showed a confirmed ORR of 57.7% (in 52 patients), with a complete responses seen in 1.9% of patients and partial responses in 55.8% of patients, all with a median duration of response of 8.7 months.
Wrapped up with Boehringer's new durability data were encouraging results from an exploratory cohort of Lung-1, in which zongertinib achieved a disease control rate of 65% in previously treatment patients with HER2 mutations outside of the TKD. Meanwhile, in another cohort of those with HER2 mutations in the TKD who were previously treated with chemotherapy and HER2-directed ADCs, 97% of patients saw disease control and the overall response rate stood at 48%.
Zongertinib is a “pipeline within a product” for Boehringer and could make a “huge impact to so many cancer patients,” Canamasas said. The drug is also being studied in a phase 3 trial that weighs it against the standard of care in first line HER2-mutated NSCLC, plus in an ongoing pan-tumor trial