Clinical trial NCT05463224: Lazertinib for NSCLC Harboring Activating EGFR Mutations in TKI naïve Patients
Official title: Lazertinib for NSCLC Harboring Activating EGFR Mutations in TKI naïve Patients: A Single-arm, Phase II Single-center Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: NSCLC
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
First posted: 2022-07-18
Enrollment: 150
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: A single-arm, phase II single-center trial
Primary purpose: TREATMENT

Brief summary: The primary objective is to evaluate the efficacy/safety of lazertinib and to explore the resistance mechanism of lazertinib as first-line in patients with NSCLC harboring activating EGFR mutations.

Detailed description: As the 3rd generation EGFR TKI become a standard treatment option for the 1st line therapy in EGFR mutated patients, necessity for evaluating resistant mechanism to determine the matched subsequent therapeutic option has been highlighted. The idea of understanding the exact resistance mechanism to 1st line 3rd generation EGFR TKI treatment is emphasized based on the observation that resistance mechanism is different based on osimertinib used as 1st line or 2nd line treatment.6,7 Although resistance mechanisms to lazertinib in patients with prior EGFR TKI treatment have been studied, there are no current data available regarding the resistance mechanism after first-line lazertinib treatment.

Based on this observation, PI designed this study to elucidate the efficacy/safety of Lazertinib and to explore resistance mechanisms of 1st line lazertinib treatment in NSCLC patients with activating EGFR mutation.

Eligibility criteria: Inclusion Criteria:

* 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). Patients who underwent curative intent surgery or definitive CRT and experience recurrence after 6 months are eligible.
* Stage IIIC or IV by AJCC 8th edition
* Confirmed EGFR mutations (exon 19 deletion, L858R)(The result from both cell-free DNA or tissue-based DNA from the local test is allowed.)
* Age of 19 or more.
* Performance status of Eastern Cooperative Oncology Group 0 to 2.
* Expected minimum life expectancy of 12 weeks
* Adequate organ function.

  * Available to provide the adequate tissue and blood for the genomic tests- At least 15 unstained slide and 20 cc of blood at baseline (mandatory) and disease progression.
* Agreed to perform re-biopsy at the timepoint of disease progression.
* At least two weeks after the chemotherapy
* Female subjects must either be of non-reproductive potential
* Subject willing and able to comply with the protocol
* Signed written informed consent

Exclusion Criteria:

* Previously treatment with any kind of EGFR TKI (Previously chemotherapy treated patients is allowed)
* Any concurrent and/or other active malignancy that has required systemic treatment within 2 years of first dose of study drug. (allowed for participation if investigator decided that previous malignancy is cured and not need for any additional treatment)
* Uncontrolled central nervous system metastases- patient with asymptomatic brain metastases or CNS symptom manageable with TKI and evaluated by investigator can be enrolled.
* 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
* Any unresolved toxicities from prior therapy, greater than CTCAE grade 1
* Mean QT interval corrected for heart rate (QTc) ≥ 470 ms
* No measurable lesion
* Unable to swallow the product due to refractory nausea, vomiting or chornic gastrointestinal disease.

Primary outcomes:
measure: progression-free survival
timeFrame: through study completion, an average of 18.0 month
measure: Resistance mechanism analysis
timeFrame: Screening, Discontiunuation Visit
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: through study completion, an average of 18.0 month
measure: Duration of Response (DoR)
timeFrame: through study completion, an average of 18.0 month
measure: Disease control rate (DCR)
timeFrame: through study completion, an average of 18.0 month
measure: Overall survival (OS)
timeFrame: through study completion, an average of 18.0 month
measure: intracranial PFS (iPFS)
timeFrame: through study completion, an average of 18.0 month
measure: intracranial ORR (iORR)
timeFrame: through study completion, an average of 18.0 month
measure: intracranial DCR (iDCR)
timeFrame: through study completion, an average of 18.0 month
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Gangnamgu
Study officials:
References: