Long-term efficacy of amivantamab in pretreated NSCLC patients with EGFR exon 20 insertion mutations

In the CHRYSALIS study, the bispecific EGFR-MET monoclonal antibody amivantamab led to a median overall survival of 23 months in patients with non-small cell lung cancer (NSCLC) with EGFR Exon 20 insertion mutations after progression on platinum-based chemotherapy. Results were consistent in subgroups of patients including the elderly, those with multiple prior treatment lines and those who where platinum-sensitive or -refractory.

Exon 20 insertion mutations (Ex20ins) are common in non-small cell lung cancer (NSCLC). Amivantamab, an EGFR and MET bispecific antibody with immune cell-directing activity, is approved to treat patients with EGFR Ex20ins advanced NSCLC whose disease progressed on platinum-based chemotherapy. The CHRYSALIS study evaluated amivantamab monotherapy among post-platinum patients at the recommended phase II dose (1,050 mg for those <80 kg and 1,400 mg for those ≥80kg). Previous results, with a median follow-up of 9.7 months, demonstrated an overall response rate (ORR) of 40%, with a duration of response of 11.1 months. Now, long-term results for the patients with EGFR Ex20ins advanced NSCLC whose disease progressed on platinum-based chemotherapy were presented.

Study design

Patients with EGFR Ex20ins advanced NSCLC whose disease progressed on platinum-based chemotherapy were recruited in CHRYSALIS. Patients who received the approved phase II dose of 1,050 mg (1,400 mg, ≥80 kg) by 8 June 2020 were included in the analyses. Response was assessed by investigator per RECIST v1.1.

Results

A total of 114 heavily-pretreated patients were included in the analysis. Median age of the patients was 62 years, 61% were female, 57% were non-smokers and 25% had baseline brain metastases. The median (range) of prior treatment lines was 2 (1-7). At a median follow-up of 19.2 months, the investigator-assessed ORR was 37%, with a median duration of response of 12.5 months. Amivantamab demonstrated consistent efficacy regardless of prior therapies (ORRs of 42.0% for prior immunotherapy and 52.2% for prior EGFR tyrosine kinase inhibitor therapy) or response to prior platinum chemotherapy (ORRs of 36.2% for patients with response or stable disease and 31.2% of those with disease progression). As previously presented, there were no differences for the subgroups by age, sex, race, baseline ECOG PS, number of prior lines, smoking history or baseline brain metastases. Median treatment duration was 7.5 months. The median progression-free survival (PFS) was 6.9 months, with a two-year PFS rate of 13.7%. Median overall survival (OS) was 23 months, with a two-year landmark OS rate of 47.2%. Forty-eight patients (42%) had sustained clinical benefit with amivantamab (defined as receipt of amivantamab for at least 12 cycles) and this was associated with an ECOG performance status of 0, achieving at least a partial response and not having baseline alterations in the RAS/RAF/MEK pathway. Among 15 patients who received amivantamab for a median of 2.6 years, 7 remained progression-free. No new safety signals were detected. Treatment-related dose interruptions, reductions and discontinuations were reported in respectively 29%, 18% and 7% of patients. Cumulative grouped rash (89%) and infusion-related reactions (67%) remained the most frequent toxicities.

The phase III PAPILLON study (NCT04538664) is investigating amivantamab plus chemotherapy vs. chemotherapy in the frontline EGFR Ex20ins NSCLC setting.

Conclusion

After a median of two prior lines of therapy and a median follow-up of 19.2 months, the median OS with amivantamab was 23 months, with a two-year landmark OS of 47%. Among post-platinum patients with EGFR Ex20ins advanced NSCLC, amivantamab demonstrated consistent efficacy regardless of prior therapy type. Furthermore, a sustained clinical benefit for at least 12 cycles was associated with a good performance status, having a response and not having baseline alterations in the RAS/RAF/MEK pathway. Finally, no new safety signals were detected.

Reference

Garrido Lopez P, et al. Long-term efficacy, safety, and predictors of response to amivantamab among patients with post-platinum EGFR Ex20ins-mutated advanced NSCLC. Presented at ELCC 2023; Abstract 3O.