Amivantamab-vmjw, an EGFR and MET bispecific monoclonal antibody, has demonstrated encouraging long-term benefits and consistent efficacy in patients with advanced non–small cell lung cancer (NSCLC) with EGFR exon 20 insertions, according to data presented by Pilar Garrido, MD, PhD, Associate Professor of Oncology at the Universidad de Alcalá and Head of the Medical Oncology Department at the University Ramón y Cajal Hospital in Madrid, at the European Lung Cancer Congress 2023.¹

Pilar Garrido, MD, PhD,

Results of the phase I CHRYSALIS study showed a median overall survival of 23 months with amivantamab therapy and a 2-year landmark overall survival rate of 47%. Treatment remains ongoing in 13% of patients who have received amivantamab for a median of 2.6 years. Amivantamab demonstrated consistent efficacy in patients with EGFR exon 20 insertion NSCLC after platinum treatment, regardless of the prior therapy type, authors of the study reported.

“Amivantamab demonstrated robust efficacy that was consistently observed across post–platinum therapy patients with EGFR exon 20 insertions, including the elderly and those with multiple prior lines of therapy, and regardless of previous response to platinum-based chemotherapy,” said Dr. Garrido. “This treatment offers hope for patients who have exhausted other treatment options.”

As she explained, exon 20 insertions represent the third most common EGFR mutation in NSCLC, accounting for approximately 12% of cases. Amivantamab, which has immune cell–directed activity, is approved to treat patients with EGFR exon 20 insertion advanced NSCLC who experience disease progression on platinum-based chemotherapy.

CHRYSALIS Study: Methods and Rationale

The CHRYSALIS study was designed to evaluate the role of amivantamab as monotherapy in a subgroup of patients with advanced NSCLC and EGFR exon 20 insertions who had already received platinum-based chemotherapy. Previous research has shown the promise of amivantamab in this patient population, with a response rate of 40% and a duration of response of 11.1 months in initial results presented at the 2020 World Conference on Lung Cancer meeting (which was actually held in January 2021).² The long-term results from the CHRYSALIS study aimed to further investigate the efficacy and safety of amivantamab in this cohort of patients.

A total of 114 heavily pretreated patients were included in the analysis, with a median age of 62 years; 61% of patients were female. There were no significant differences based on race. About 25% of the patients had received radiotherapy for baseline brain metastases before enrolling in the clinical trial, with a median number of prior lines of therapy ranging from one to seven.

With a median follow-up of 19 months, the overall response rate was 37%, and the median duration of response was 12.5 months. Dr. Garrido emphasized that amivantamab demonstrated consistent efficacy regardless of prior therapy type.

“More than 40% of patients had received prior immunotherapy, and 20% of patients had received prior EGFR [tyrosine kinase inhibitors],” said Dr. Garrido. “Amivantamab also exhibited consistent efficacy irrespective of the type of prior response to platinum-based chemotherapy.”

Subgroup analyses revealed no differences in efficacy based on age, sex, race, baseline Eastern Coopertive Oncology Group (ECOG) performance status, number of prior lines of therapy, smoking history, or baseline brain metastases status. However, sustained clinical benefit—defined as receiving amivantamab for 12 or more cycles—was associated with an ECOG performance status of 0, having a response according to Response Evaluation Criteria in Solid Tumors, and not having baseline plasma alterations in the RAS/RAF/MEK pathway.

Among the 114 patients analyzed, 48 (42%) experienced sustained clinical benefit, and 15 patients (13%) continued treatment for a median duration of 2.6 years at the data cutoff. The median progression-free survival was 6.9 months, with a 2-year progression-free survival rate of 13.7%.

No new safety signals were detected after long-term follow-up. Most adverse events were grade 1 and 2 toxicities, such as rash (89%) and infusion-related reactions. Treatment-related dose interruptions occurred in 29% of patients; dose reduction was needed in 18%; and just 7% required discontinuation of therapy because of adverse events.

Predictive Biomarkers and Future Research

Potential predictive biomarkers were also investigated using baseline plasma samples for circulating tumor DNA analysis with the genomic profile test. Interestingly, said Dr. Garrido, no patients who received more than 12 cycles of amivantamab had baseline alterations in the RAS/RAF/MEK pathway, with such alterations observed only in patients who received fewer than 12 cycles.

Amivantamab is currently being explored in the phase III -PAPILLON study, which is investigating amivantamab plus chemotherapy vs chemotherapy alone in the front-line EGFR exon 20 insertion NSCLC setting. The outcomes of the PAPILLON study will further elucidate the role of amivantamab in improving the upfront management of patients with advanced NSCLC and EGFR exon 20 insertions, Dr. Garrido concluded. 

DISCLOSURE: Dr. Garrido reported financial relationships with AbbVie, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, GlaxoSmithKline, Janssen, Lilly, Medscape, MSD, Novartis, Pfizer, Roche, Sanofi, Takeda, and Touch Medical.

REFERENCES

1. Garrido P, Girard N, Cho BC, et al: Amivantamab in post-platinum EGFR exon 20 insertion advanced non-small cell lung cancer: Long-term follow-up from the CHRYSALIS study. European Lung Cancer Congress 2023. Abstract 30. Presented March 29, 2023.

2. Sabari JK, Shu CA, Park KS, et al: Amivantamab in post-platinum EGFR exon 20 insertion mutant non-small cell lung cancer. J Thorac Oncol 16(suppl 3):S108-S109, 2021.