First-Line Amivantamab Plus Lazertinib Demonstrates Promise in Patients With Advanced EGFR-Mutated Non-Small Cell Lung Cancer

Benjamin Besse, MD, PhD, Gustave Russe Institute, Paris, France, discusses early analysis results from the MARIPOSA study which demonstrated that amivantamab plus lazertinib has promising antitumor activity among patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC).  

Dr Besse presented these results at the 2024 European Society of Medical Oncology (ESMO) Congress in Barcelona, Spain. 

Transcript: 

Hi, I am Benjamin Besse. I'm a medical oncologist from Gustave Russe in Paris, France, and I'm here at ESMO 2024 to report the results of mechanism of resistance in 2 of the arms of the MARIPOSA study. 

MARIPOSA is a first-line study in patients with EGFR-mutated non-small cell lung cancer and it has compared 3 arm[s], but we will deal with two arms that are amivantamab, a bispecific EGFR and MET antibody, plus lazertinib, a third generation TKI-inhibitor, and it was compared to osimertinib. 

We know first-line very well that the resistance mechanism to osimertinib is mostly driven by EGFR and MET pathway dysregulation. We don't know yet very well what the mechanisms of resistance to amivantamab and lazertinib – that is a combination that can be given first-line and is approved in the US. Here we have collected samples, blood biopsy before and at the end of the treatment, when the treatment was discontinued or within 90 days, and we have compared the baseline and the match liquid biopsy at the end of the treatment. Roughly, in each arm, 429 patients were enrolled, and we have around 120 to 140 patients, in each arm, patients with the paired liquid biopsy. 

What is the learning here– the learning is that using a [G]360 NGS panel on the circulating tumor DNA, we were able to detect 13.6% of MET amplification in the [osimertinib] arm, this is exactly what we expect. In the [amivantamab-lazertinib] arm it drops to 4.3%, so almost a threefold reduction. Interestingly, with the EGFR-resistant mutation in 8.9% of the patients in the [osimertinib] arm, this is what is expected, but it dropped to 0.9% in the [amivantamab-lazertinib] arm, demonstrating that this drug potentially has activity by inhibiting both EGFR and MET when some could think that it was more a MET directed drug. Regarding the other resistance, the other pathway, that could explain resistance to this drug, they were roughly similar between the 2 arms, maybe a bit more R2 amplification after [amivantamab-lazertinib] and interestingly, a bit less TP53 RB1 loss, which is a pattern that reflects the small cell lung cancer transformation, 2.9% in the [osimertinib] arm, 0.9% in the [amivantamab-lazertinib] arm. 

Overall, the study demonstrates that amivantamab is a potent inhibitor against both EGFR and MET and in combination with lazertinib the resistance mechanism today cannot really give us a clue on what to prescribe next at the time of resistance, but this is a story that is ongoing. We present only the first patients that progress. A lot of patients, 214 in the [amivantamab-lazertinib] are still on treatment. I hope this data set will be more enriched, both in number of samples and in the type of analysis, to understand how we can best treat these patients after first-line treatment. Thank you.

Source: 

Besse B, Lee SH, Lu S, et al. Mechanisms of acquired resistance to first-line amivantamab plus lazertinib versus osimertinib in patients with EGFR-mutant advanced non-small cell lung cancer: An early analysis from the phase III MARIPOSA study. Presented at 2024 ESMO Congress. September 13-17, 2024. Abstract LBA55