LBA54

The Phase III MARIPOSA-2 study evaluated amivantamab plus chemotherapy (carboplatin/pemetrexed) versus chemotherapy alone in patients with EGFR-mutated advanced NSCLC who had progressed on osimertinib.

Overall Survival (OS):

• Median OS was improved with amivantamab plus chemotherapy (17.7 months) compared to chemotherapy alone (15.3 months), with a hazard ratio (HR) of 0.73. However, this did not meet the prespecified significance threshold.

•  At 18 months, survival rates were 50% for amivantamab-chemo and 40% for chemo alone.

Progression-Free Survival after First Subsequent Therapy (PFS2):

• Amivantamab-chemo significantly extended PFS2 to 16.0 months versus 11.6 months for chemo alone, suggesting prolonged post-progression outcomes.

Time to Treatment Discontinuation (TTD) and Time to Subsequent Therapy (TTST):

• TTD and TTST were significantly prolonged in the amivantamab-chemo group (TTD: 10.4 months vs 4.5 months, TTST: 12.2 months vs 6.6 months, respectively).

Conclusion –

The addition of amivantamab to chemotherapy improved post-progression outcomes, including PFS2, TTD, and TTST compared to chemotherapy alone. While OS showed a favorable trend, it did not reach statistical significance. These results underscore the potential of amivantamab in delaying disease progression in EGFR-mutated NSCLC after osimertinib failure.

LBA55

This study was part of the Phase III MARIPOSA trial, which compared amivantamab plus lazertinib to osimertinib as first-line treatment for EGFR-mutant advanced NSCLC. It focused on mechanisms of acquired resistance in patients who progressed on these treatments.

Patients receiving amivantamab-lazertinib had significantly lower rates of acquired resistance mutations compared to those on osimertinib:

• MET amplification (4.4% vs 13.6%; p=0.017)

• Other EGFR resistance mutations such as C797S, L718X, and G724X (0.9% vs 7.9%; p=0.014)

• TP53 resistance mutations (9.7% vs 12.9%)

RB1 loss of function (associated with small cell transformation) was less frequent in the amivantamab-lazertinib group (0.9% vs 2.9%).

Conclusion –

This analysis demonstrated that amivantamab-lazertinib altered the biology of acquired resistance compared to osimertinib by reducing key resistance mutations such as MET amplification and EGFR mutations. These early findings suggest that amivantamab may be more effective in delaying resistance and disease progression in EGFR-mutant NSCLC.

For more insight into the patient's burden/epidemiology, treatment, and changing market landscape-related advancements, refer to the following reports:

• Metastatic Non-Small Cell Lung Cancer - Market Insight, Epidemiology and Market Forecast -2034

• Epidermal Growth Factor Receptor-Non Small Cell Lung Cancer (EGFR-NSCLC) - Market Insight, Epidemiology And Market Forecast - 2032