Non-Small Cell Lung Cancer MetastaticPhase 2NCT06106802
Lazertinib & Tepotinib for EGFR Mutant NSCLC in MET Overexpressed or Amplified Who Progressed After Lazertinib Treatment
A Phase 2 study testing Lazertinib and Tepotinib in people with Non-Small Cell Lung Cancer Metastatic, run by Sehhoon Park at 1 site in South Korea.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer Metastatic
- What is being tested?
- Lazertinib and Tepotinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 1 siteSouth Korea
- Study dates
- 11 Jun 2024to 30 Sep 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer which is not amenable to treatment with a curative aim (e.g., surgery or radiation)
- Confirmed EGFR mutations (exon 19 deletion, L858R) with acquired resistance after first-line lazertinib treatment (either partial response, complete response or stable disease last more than 6 months after initiation of Lazertinib) - patient can maintain the treatment with prior EGFR treatment as beyond progression until the patient start the treatment per this protocol
- First-line cytotoxic chemotherapy received as palliative treatment is acceptable after the failure of Lazertinib (Patients with disease progression after adjuvant or neoadjuvant chemotherapy within 6 months are eligible to participate)
- Patient with MET amplification FISH GCN ≥5 and/or MET/CEP7 ≥ 2 (If additional resistance mechanism to lazertinib, such as C797S, is observed with MET amplification, the recruitment needs to be discussed in advance with the principal investigator)
- Available tissue for MET FISH
- Age of 19 or more
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- Performance status of Eastern Cooperative Oncology Group 0 to 2
- Expected minimum life expectancy of 12 weeks
- Adequate organ function
- Absolute neutrophil count (ANC) ≥1500cells/mm3
- Platelet count ≥100,000cells/mm3
- Total bilirubin ≤1.5 x upper limit of normal(ULN)
- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN (or ≤5.0 x ULN, if liver metastasis is present)
- Creatinine level ≤1.5 x upper limit of normal (ULN) or creatinine clearance ≥ 45mL/min (Calculated with Cockcroft- Gault equation)
- Available to provide the adequate tissue and blood for the genomic tests
- At least 20 unstained slide and 20 cc of blood at baseline and disease progression (If not, participant must be confirmed by the principal investigator
- Agreed to perform re-biopsy at the timepoint of disease progression
- Female subjects must either be of non-reproductive potential
- Subject willing and able to comply with the protocol
- Signed written informed consent
Who cannot join
- Previously treatment with any kind of EGFR TKI other than lazertinib
- All concurrent and/or other active malignant tumors requiring systemic therapy within 2 years prior to the initial administration of the investigational drug (However, the patient may participate if previous malignant tumor has been cured, and no further treatment is required)
- Uncontrolled central nervous system metastases
- Spinal cord compression, leptomeningeal carcinomatosis
- Uncontrolled systemic illness, including uncontrolled hypertension, active bleeding, or active infection
- Radiotherapy with a wide field of radiation within 2 weeks or radiotherapy with a limited field of radiation (localized radiotherapy or gamma knife surgery) for palliation within 1 week
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- Any unresolved toxicities from prior therapy, greater than CTCAE grade 1
- Prior history of interstitial lung disease (ILD) or ILD like symptoms
- Mean QT interval corrected for heart rate (QTc) ≥ 470 ms
- No measurable lesion
- Unable to swallow the product due to refractory nausea, vomiting or chronic gastrointestinal disease
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
South Korea1 site, 1 recruiting
- Recruiting
Samsung Medical Center
Seoul, Gangnam-gu, 06351
Sehhoon Park, M.D., 82-2-3410-3746, sehhoon.park@samsung.com
Sehhoon Park, M.D.
About this study
Official title: Lazertinib and Tepotinib for EGFR Mutant NSCLC in MET Overexpressed or Amplified Who Progressed After Lazertinib Treatment: A Phase II Multi-center Trial
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))
Read more
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
- Being tested
- Lazertinib, Tepotinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LazertinibDrug
Lazertinib 240mg/day
TepotinibDrug
Tepotinib 500mg/day
| Study group | Role | What they receive |
|---|---|---|
| single arm | Experimental | Patients will be treated with Lazertinib + tepotinib based on the MET FISH results.
Lazertinib 240mg daily Tepotinib 500mg daily Receives: Drug: Lazertinib; Drug: Tepotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
objective response rate (ORR)
Measured: 9 months after completion of enrollment
Secondary outcomes (4)
Progression free survival (PFS)
Measured: up to 60 months
Duration of Response (DoR)
Measured: up to 60 months
Disease control rate (DCR)
Measured: up to 60 months
Overall survival (OS)
Measured: up to 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2023
- Study start11 Jun 2024
- Primary completion30 Sep 2029 (estimated)
- Study completion30 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Small Cell Lung Cancer MetastaticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sehhoon Park
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Sehhoon Park, Samsung Medical Center
- Investigators
- Sehhoon Park, Principal investigator, Samsung Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06106802
- Sponsor's protocol ID
- 2023-10-053
- Status last verified
- Feb 2026
- First submitted
- 12 Oct 2023
- Last updated
- 10 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lazertinib and Tepotinib for EGFR Mutant NSCLC in MET Overexpressed or Amplified Who Progressed After Lazertinib Treatment: A Phase II Multi-center Trial
- ClinicalTrials.gov ID
- NCT06106802
- Acronym / sponsor ID
- 2023-10-053
- Conditions
- Non-Small Cell Lung Cancer Metastatic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 47 participants (estimated)
- Lead sponsor
- Sehhoon ParkUniversity, hospital or other
- Study start
- 11 Jun 2024 (actual)
- Primary completion
- 30 Sep 2029 (estimated)
- Study completion
- 30 Sep 2029 (estimated)
- First posted
- 30 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| single arm | Experimental | Drug: Lazertinib, Drug: TepotinibPatients will be treated with Lazertinib + tepotinib based on the MET FISH results. Lazertinib 240mg daily Tepotinib 500mg daily |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer which is not amenable to treatment with a curative aim (e.g., surgery or radiation)
- Confirmed EGFR mutations (exon 19 deletion, L858R) with acquired resistance after first-line lazertinib treatment (either partial response, complete response or stable disease last more than 6 months after initiation of Lazertinib) - patient can maintain the treatment with prior EGFR treatment as beyond progression until the patient start the treatment per this protocol
- First-line cytotoxic chemotherapy received as palliative treatment is acceptable after the failure of Lazertinib (Patients with disease progression after adjuvant or neoadjuvant chemotherapy within 6 months are eligible to participate)
- Patient with MET amplification FISH GCN ≥5 and/or MET/CEP7 ≥ 2 (If additional resistance mechanism to lazertinib, such as C797S, is observed with MET amplification, the recruitment needs to be discussed in advance with the principal investigator)
- Available tissue for MET FISH
Key exclusion criteria (11 listed)
- Previously treatment with any kind of EGFR TKI other than lazertinib
- All concurrent and/or other active malignant tumors requiring systemic therapy within 2 years prior to the initial administration of the investigational drug (However, the patient may participate if previous malignant tumor has been cured, and no further treatment is required)
- Uncontrolled central nervous system metastases
- Spinal cord compression, leptomeningeal carcinomatosis
- Uncontrolled systemic illness, including uncontrolled hypertension, active bleeding, or active infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LazertinibLazertinib 240mg/day | Drug | single arm |
| TepotinibTepotinib 500mg/day | Drug | single arm |
Primary outcome
objective response rate (ORR)
Time frame: 9 months after completion of enrollment
4 secondary outcomes
Progression free survival (PFS)
Time frame: up to 60 months
Duration of Response (DoR)
Time frame: up to 60 months
Disease control rate (DCR)
Time frame: up to 60 months
Overall survival (OS)
Time frame: up to 60 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Sehhoon Park principal investigator
Samsung Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lazertinib and Tepotinib in people with Non-Small Cell Lung Cancer Metastatic, run by Sehhoon Park at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sehhoon Park (82-10-3410-3746, sehhoon.park@samsunng.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
objective response rate (ORR) (time frame: 9 months after completion of enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2026.