Trial results for the Phase 3 study NCT04988295, investigating amivantamab and lazertinib in combination with platinum-based chemotherapy, were posted on ClinicalTrials.gov on 2025-04-16. The study showed that the combination of lazertinib, amivantamab, carboplatin, and pemetrexed (LACP/ACP-L) extended median progression-free survival (PFS) to 8.31 months compared to 4.17 months for platinum-based chemotherapy alone in patients with EGFR-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) after osimertinib failure.
Background
The study NCT04988295 investigated treatment options for patients with epidermal growth factor receptor (EGFR)-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) after osimertinib failure. This population includes those with EGFR Exon 19del or Exon 21 L858R substitution.
Trial design
The study NCT04988295 was a Phase 3 trial that enrolled 776 participants with epidermal growth factor receptor (EGFR)-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) after osimertinib failure. Specifically, the study focused on patients with EGFR Exon 19del or Exon 21 L858R substitution. The trial compared several treatment arms: Arm A involved lazertinib, amivantamab, carboplatin, and pemetrexed (LACP/ACP-L dosing strategies); Arm C involved amivantamab, carboplatin, and pemetrexed (ACP); and Arm B, the comparator arm, involved carboplatin and pemetrexed (CP). Progression-free survival (PFS) was assessed by Blinded Independent Central Review (BICR) according to RECIST Version 1.1.
Key results
The trial results showed differences in progression-free survival (PFS) across the treatment arms. For the outcome of "Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Blinded Independent Central Review (BICR)":
- In Main Study: Arm A: Lazertinib + Amivantamab + Carboplatin + Pemetrexed (LACP/ACP-L), the median PFS was 8.31 months.
- In Main Study: Arm B: Carboplatin + Pemetrexed (CP), the median PFS was 4.17 months.
- In Main Study: Arm C: Amivantamab + Carboplatin + Pemetrexed (ACP), the median PFS was 6.28 months.
Key analyses further supported these findings:
- A Log Rank analysis comparing Arm A (LACP/ACP-L) to Arm B (CP) reported a Hazard Ratio (HR) of 0.44 (95.0% CI: 0.35 to 0.56) with a p-value of 0.0001.
- A Log Rank analysis comparing Arm C (ACP) to Arm B (CP) reported a Hazard Ratio (HR) of 0.48 (95.0% CI: 0.36 to 0.64) with a p-value of 0.0001.
What this means
The results from this Phase 3 study suggest that adding amivantamab and lazertinib to platinum-based chemotherapy, or amivantamab alone with chemotherapy, significantly improves progression-free survival for patients with EGFR-mutated NSCLC who have progressed after osimertinib. The substantial reduction in the risk of progression, as indicated by the Hazard Ratios of 0.44 and 0.48, and the extended median PFS in the experimental arms compared to chemotherapy alone, highlight the potential benefit of these combination therapies in this challenging patient population.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04988295, titled "A Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non- Small Cell Lung Cancer After Osimertinib Failure," were posted on 2025-04-16 on clinicaltrials.gov.