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Lazertinib & Tepotinib for EGFR Mutant NSCLC in MET Overexpressed or Amplified Who Progressed After Lazertinib Treatment

NCT06106802 · Status: RECRUITING · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 47

Last updated 2026-02-23

No results posted yet for this study

Summary

As the 3rd generation, EGFR TKI has become a standard treatment option for the 1st line therapy in EGFR mutated patients, the necessity for evaluating resistant mechanism to determine the matched subsequent therapeutic option has been highlighted. From the 1st line Osimertinib treatment, the heterogenous resistance mechanism has been observed showing most commonly by MET amplification (7-15%) followed by additional on-target EGFR mutation (6-10%), BRAF, PI3KCA, KRAS, HER2 mutation (13-14%) and still 40 to 50% remain unknown for the mechanism. (A. Leonetti et al.British Journal of Cancer(2019))

Based on the observation showing the MET amplification as the most common resistance mechanism to the 3rd generation EGFR TKI treatment, the "TATTON" study, a multi-arm, phase IB trial, demonstrated early clinical data of Osimertinib in combined with savolitinib. Among the patients, c-MET amplified patients who were previously treated with 3rd generation EGFR TKI, a combination of Osimertinib and savolitinib, showed an objective response rate of 33% and median PFS of 5.5 months. (G. Oxnard et al. Annals of Oncology(2020))

The clinical efficacy of Osimertinib with savolitinib in MET overexpressed or amplification patients are reported from the global phase II, "SAVANNAH" study. The preliminary results from the SAVANNAH trial showed that Osimertinib plus savolitinib demonstrated an objective response rate of 49% in patients with a high level of MET overexpression and/or amplification, defined as IHC90+ and/or FISH 10+, whose disease progressed on treatment with Osimertinib. The highest ORR was observed in patients with a high level of MET who were not treated with prior chemotherapy (52%). In patients whose tumors did not show a high level of MET, the ORR was 9% (MJ Ahn, WCLC, 2022). There are ongoing global Phase III SAFFRON study to validate the outcome from SAVANNAH study.

It has been reported that around 62% of tumor in Osimertinib progressed sample has MET overexpression and/or amplification, and more than one-third (34%) met the defined high MET level cut-off.

As Lazertinib is about to be approved as the treatment option for the treatment naïve EGFR mutated NSCLC, it is also becoming important to develop a further treatment plan based on the MET amplification status. In this study, the investigators designed a phase II study based on the MET amplification status to evaluate the clinical efficacy of Lazertinib + tepotinib.

Conditions

  • Non-Small Cell Lung Cancer Metastatic

Interventions

DRUG

Lazertinib

Lazertinib 240mg/day

DRUG

Tepotinib

Tepotinib 500mg/day

Sponsors & Collaborators

  • Samsung Medical Center

    lead OTHER

Principal Investigators

  • Myung-Ju Ahn · Samsung Medical Center

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
19 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2024-06-11
Primary Completion
2029-09-30
Completion
2029-09-30

Countries

  • South Korea

Study Locations

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Entities

Drugs

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT06106802 on ClinicalTrials.gov