Rybrevant Plus Leclaza May Be New Standard for EGFR-Mutant Lung Cancer

Patients with EGFR-mutant non-small cell lung cancer (NSCLC) tended to live longer without their disease worsening (a statistic known as progression-free survival [PFS]) when treated with Rybrevant (amivantamab) plus Leclaza (lazertinib) compared to Tagrisso (osimertinib), according to an analysis of the MARIPOSA study.

These data, which were presented at the 2024 American Society of Clinical Oncology Annual Meeting, may lay the groundwork for Rybrevant plus Leclaza to become the new standard of care for this patient population, an expert said.

“Multiple features such as brain or liver metastases at baseline TP53 co-mutations, and EGFR ctDNA shedding are common in patients with advanced EGFR mutations and are associated with poor prognosis,” study author Dr. Enriqueta Felip, head of the Thoracic and Head and Neck Cancer Unit at Vall d’Hebron Hospital in Barcelona, Spain, said during a presentation of the findings.

This analysis of phase 3 MARIPOSA trial included data from 858 patients with EGFR-mutant (Exon 19 deletion or L858R) advanced NSCLC that has not yet been treated. Patients were randomly assigned to receive Rybrevant plus Leclaza (429 patients) or Tagrisso (429 patients).

Baseline ctDNA, which tests for cancer DNA in the blood, for analysis of pathogeneic alterations (cancer-related mutations) was available for 636 patients: 320 in the Rybrevant /Leclaza group and 316 in the Tagrisso group.

Findings showed that among patients with a TP53 co-mutation, the median PFS was 18.2 months in the combination group (149 patients), and 12.9 months in the Tagrisso group (144 patients). Patients whose disease did not have a TP53 mutation (117 and 130 in the combination and single-agent groups, respectively) did not have a significant difference in median PFS, though data showed a trend favoring Rybrevant /Leclaza, with a median PFS of 22.1 months, compared to 19.9 months. However, there was not statistically significant difference between these two PFS datapoints, meaning that researchers could not say with certainty that one is better than the other.

In patients with ctDNA detectable via droplet digital PCR (a tool used to detect cancer) at baseline, median PFS was significantly longer in the Rybrevant /Leclaza arm (231 patients) compared to the Tagrisso arm (240 patients), at 20.3 months and 14.8 months, respectively.

The drug duo also proved superior in patients with ctDNA clearance at cycle 3 day 1, with median PFS durations of 24 months (163 patients) versus 16.5 months (180 patients), respectively. ctDNA clearance means that clinicians could not detect cancer DNA in a blood test. For patients who did not clear ctDNA, PFS was 16.5 (29 patients) versus 9.1 months (32 patients), respectively.

For patients with cancer in the brain at baseline, Rybrevant /Leclaza also led to improved outcomes. Median PFS for this group was 18.3 months for those given the combination (178 patients) and 13 months for those given Tagrisso (172 patients). This, according to the researchers, is consistent with the PFS benefit observed with Rybrevant plus Leclaza in patients with a history of brain metastases.

Regarding liver metastases, at a median follow-up of 22 months, the median PFS was 18.2 months and 11 months in the amivantamab/lazertinib groups, respectively.

“High-risk features occur commonly in first line EGFR-mutant [NSCLC] and carry a poor prognosis,” Felip said. “Amivantamab plus lazertinib produces superior PFS outcomes in patients with high-risk features and represents a promising new standard of care treatment option in first line EGFR-mutant [NSCLC].”

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