Rybrevant data showed long-term clinical response and safety in advanced NSCLC with EGFR exon 20 insertion mutations in patients who have failed prior platinum-based chemotherapy
The Janssen Pharmaceutical Companies of Johnson & Johnson announced new long-term data from the CHRYSALIS study evaluating Rybrevant (amivantamab-vmjw) in patients with advanced non-small cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) exon 20 insertion mutations whose disease progressed on prior platinum-based chemotherapy. Data from the study showed long-term response and safety in this population and were presented in an oral presentation at the 2023 European Lung Cancer Congress (ELCC) (Abstract #779)
In the analysis of the CHRYSALIS study- investigators assessed the efficacy and safety of Rybravant in patients (n=114) with NSCLC and EGFR exon 20 insertion mutations, who had progressed on prior platinum-based IIchemotherapy, and were treated at the approved Phase II dose of 1050 mg (1400 mg for a patient weight of at least 80 kg). The primary endpoint was overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Additional endpoints included duration of response (DOR), clinical benefit rate, progression-free survival (PFS) and overall survival (OS).
Results After a median follow-up of 19.2 months, the median OS with Rybrevant treatment was 23 months (95 percent Confidence Interval [CI], 18.5–29.5) with a two-year OS rate of 47 percent. The investigator-assessed ORR was 37 percent (95 percent CI, 28–46) with a median DOR of 12.5 months (95 percent CI, 6.9–19.3), and median PFS of 6.9 months (95 percent CI, 5.6-8.8). Across subgroups, treatment with Rybevant resulted in consistent efficacy across post-platinum patients with EGFR exon 20 insertion mutations, including the elderly, regardless of prior therapies or response to prior platinum chemotherapy. Forty-eight patients (42 percent) had sustained clinical response measured by ORR on Rybrevent for at least 12 cycles. The median duration of treatment was 7.5 months and treatment is ongoing in 15 patients (13 percent) who have received Rybrevant for a median of 2.6 years. Of these patients, seven are progression-free and eight are receiving treatment beyond progression.
No new safety signals were identified and rash (all group, 89 percent), infusion-related reactions (IRR; 67 percent) and paronychia (58 percent) remained the most common treatment emergent adverse events (AEs).1 The incidence of treatment-related AEs leading to dose interruption, reduction and discontinuation was 29 percent, 18 percent and seven percent, respectively.
NSCLC driven by EGFR exon 20 insertion mutations carries a worse prognosis and shorter survival rates compared with lung cancer driven by more common EGFR mutations, such as exon 19 deletions and L858R substitutions.2 The standard of care for common EGFR mutations, such as EGFR tyrosine kinase inhibitor (TKIs), are generally inactive against exon 20 insertion mutations and are not FDA-approved for these patients.