Hope blossoms for those battling non-small cell lung cancer (NSCLC)! A new oral treatment, sevabertinib, is showing real promise, especially for patients with specific HER2 or EGFR mutations. This could be a game-changer.
This encouraging news comes from a phase 1/2 clinical trial (NCT05099172), which demonstrated that sevabertinib (BAY2927088) is both safe and effective. The trial focused on NSCLC patients whose tumors had HER2 or EGFR mutations.
Sevabertinib delivered impressive results: rapid, sustained, and clinically meaningful antitumor activity. The objective response rates (ORRs) varied, but all were encouraging:
- 64% ORR in patients previously treated but new to HER2-targeted therapy.
- 38% ORR in patients previously treated with a HER2 antibody-drug conjugate (ADC).
- 71% ORR in patients who had not received any prior treatment.
The median duration of response (DOR) was also noteworthy: 9.2 months, 8.5 months, and 11 months, respectively. Progression-free survival (PFS) was 8.3 months and 5.5 months, with data still developing for the treatment-naive group. Interestingly, patients with brain metastases responded similarly to those without.
But here's where it gets controversial... The most common side effect was mild diarrhea (grade 1 or 2). While 31% of patients experienced grade 3 or higher side effects, only 3% had to stop treatment due to these effects. A significant positive is the absence of interstitial lung disease or pneumonitis, a serious risk sometimes seen with HER2-targeted therapies.
As the study authors, Siegel et al., pointed out, patients with HER2 exon 20 insertions currently face limited treatment options. They highlighted the need for effective, well-tolerated oral therapies, even with the accelerated approvals of trastuzumab deruxtecan (T-DXd, Enhertu) and zongertinib (Hernexeos).
So, who was eligible for this trial? Patient criteria included:
- A confirmed diagnosis of locally advanced NSCLC unsuitable for definitive therapy.
- Documented disease progression after prior treatment.
- Adequate tumor tissue for analysis.
- Measurable disease according to RECIST v1.1 criteria.
And who was excluded? Patients who:
- Had received an EGFR tyrosine kinase inhibitor (TKI) within 8 days or 5 times the terminal phase.
- Had systemic anticancer treatment within 14 days.
- Had radiation therapy within 14 days.
What was the trial like? Sevabertinib is an oral, reversible HER2 TKI. Patients were divided into three groups: those previously treated but new to HER2-targeted therapy, those previously treated with HER2-directed ADCs, and treatment-naive patients. The study aimed to determine the optimal dose and assess its effectiveness. Patients took sevabertinib orally, once or twice daily, in 3-week cycles.
What's next for Sevabertinib?
- An expanded access program (NCT06761976) is underway, providing access to sevabertinib for patients with advanced NSCLC and HER2 mutations.
- A phase 2 panSOHO study (NCT06760819) is exploring the drug's effectiveness in various solid tumors with HER2 mutations.
What do you think? Does this new treatment approach offer a significant step forward in lung cancer treatment? Are you encouraged by the results? Share your thoughts in the comments below!
