Nicolas Girard, Chief of Medical Oncology at Institut Curie in Paris. At ESMO 2023, I will discuss the results from the PAPILLON study, which is a randomized study which assessed amivantimab plus chemotherapy versus chemotherapy alone in patients with EGFR exon 20 insertion-mutated non-small cell lung cancer. This is a small subset of patients with non-small cell lung cancer, about 1% to 3% of the patients, who have a tumor with an EGFR exon 20 insertion mutation. Very different from the common EGFR mutation, because in EGFR exon 20 insertion-mutated non-small cell lung cancer, the efficacy of the common EGFR TKI is very, very low and limited. The standard of care for this patient has remained chemotherapy based on platinum.

Amivantimab is a bispecific EGFR and MET antibody, which previously demonstrated anti-tumor activity in those patients, and is currently approved for further treatment after progression on chemotherapy. PAPILLON is a randomized study, 308 patients, randomized 1-to-1 to receive amivantimab plus chemotherapy or chemotherapy alone. We have a crossover in this trial, meaning that patients receiving chemotherapy alone were allowed to receive amivantimab monotherapy in the second line setting after disease progression. The primary end point is a progression-free survival [PFS] by blinded independent central review.

The rationale to combine amivantimab with chemotherapy is that we are combining the immune cell directing activity of amivantimab with that of chemotherapy-induced cell deaths. We have preliminary data from the CHRYSALIS phase one study which showed that we may achieve partial responses in those patients with the combination in the first line setting. At the end, 308 patients, majority of patients had discontinued at the time of the cutoff, mostly for disease progression, but still we have 46% of patients in the amivantimab plus chemotherapy arm who are still on treatment at that time. Two-thirds of the patient randomized to receive chemotherapy alone had crossover to amivantimab monotherapy.

The main result is that from the PFS, which is a primary endpoint of PAPILLON and this primary endpoint is met. The median progression-free survival with amivantimab plus chemotherapy is 11.4 months versus 6.7 months for chemotherapy. This has a ratio of 0.395, meaning a 60% reduction in the risk of disease progression with a combination of chemo plus amivantimab versus chemotherapy alone. This is a sustained efficacy, and we have a plateau in the survival curves, which is in line with the previous experience with amivantimab monotherapy, which may be related to this immune cell activity of amivantimab.

We have a benefit in terms of response rate. We have a benefit in terms of duration of response, PFS-2. With regard to OS, at the time of this interim analysis, median overall survival was not reached in the amivantimab plus chemotherapy arm. It was 24 months in the chemotherapy arm. This is preliminary data. We need a longer follow-up, more events, but this is promising and encouraging for this combination, again, despite the fact that we had this crossover in a large proportion of the patients in the control arm.

At the end, we have a consistent benefit with amivantimab plus chemotherapy, PFS, PFS2 response, duration of response, interim trend for overall survival. This is a first study to show a clinical benefit for these patients with EGFR exon 20 insertion mutating non-small cell lung cancer. Based on this data, we believe that amivantimab plus chemotherapy is a new standard of care in the first line setting for those patients.