New long-term data from the CHRYSALIS study evaluating amivantamab-vmjw in patients with advanced non–small cell lung cancer (NSCLC) and EGFR exon 20 insertion mutations whose disease progressed on prior platinum-based chemotherapy were presented by Lopez et al at the 2023 European Lung Cancer Congress (ELCC) (Abstract 3O). The data showed long-term responses and safety in this population.
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. The standard of care for lung cancers with common EGFR mutations—such as EGFR tyrosine kinase inhibitors—are generally inactive against exon 20 insertion mutations and are not FDA-approved for these patients.
About the CHRYSALIS Study
CHRYSALIS (ClinicalTrials.gov identifier NCT02609776) is a phase I, open-label, multicenter, first-in-human study to evaluate the safety, pharmacokinetics, and preliminary efficacy of amivantamab as a monotherapy and in combination therapies in adults with advanced NSCLC. The study consists of two parts: amivantamab monotherapy and combination-dose escalations (part 1) and amivantamab monotherapy and combination-dose expansions (part 2). The study enrolled 780 patients with advanced NSCLC.
Study Results
In the analysis of the CHRYSALIS study, investigators assessed the efficacy and safety of amivantamab, a bispecific monoclonal antibody, in patients (n = 114) with NSCLC and EGFR exon 20 insertion mutations who had disease progression on prior platinum-based chemotherapy, and were treated at the approved phase II dose of 1,050 mg (1,400 mg for a patient weight of at least 80 kg). The initial dose was received as a split infusion in week 1 on day 1 and day 2, then administered every 2 weeks thereafter until disease progression or unacceptable toxicity.
The primary endpoint of the trial was overall response rate per Response Evaluation Criteria in Solid Tumors version 1.1. Additional endpoints included duration of response, clinical benefit rate, progression-free survival, and overall survival.
After a median follow-up of 19.2 months, the median overall survival with amivantamab was 23 months (95% confidence interval [CI] = 18.5–29.5 months) with a 2-year overall survival rate of 47%. The investigator-assessed overall response rate was 37% (95% CI = 28%–46%) with a median duration of response of 12.5 months (95% CI = 6.9–19.3 months) and a median progression-free survival of 6.9 months (95% CI = 5.6–8.8 months).
Across subgroups, treatment with amivantamab resulted in consistent efficacy across postplatinum patients with EGFR exon 20 insertion mutations, including the elderly, regardless of prior therapies or response to prior platinum chemotherapy. Forty-eight patients (42%) had sustained clinical response measured by overall response rate on amivantamab for at least 12 cycles. The median duration of treatment was 7.5 months, and treatment is ongoing in 15 patients (13%) who have received amivantamab 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 (89%), infusion-related reactions (67%), and paronychia (58%) remained the most common treatment-emergent adverse events. The incidence of treatment-related adverse events leading to dose interruption, reduction, and discontinuation was 29%, 18%, and 7%, respectively.
Pilar Garrido, MD
"With these new data, amivantamab showed long-term consistent efficacy regardless of prior therapies or response to prior platinum chemotherapy," said Pilar Garrido, MD, Associate Professor of Medical Oncology at Universidad de Alcalá, Head of Medical Oncology Department at the University Hospital Ramón y Cajal in Madrid, and principal investigator of the study. "Due to the aggressive nature of NSCLC with EGFR exon 20 insertion mutations, treatment with targeted therapies is an important consideration when identifying a treatment option for patients."
Disclosure: For full disclosures of the study authors, visit oncologypro.esmo.org.
