NCT05477615

Lazertinib/Pemetrexed/Carboplatin After Osimertinib Failure in NSCLC With Brain Metastases

Phase II Trial of Lazertinib and Pemetrexed/Carboplatin Combination in Patients With EGFR Positive, Metastatic NSCLC With Asymptomatic or Mild Symptomatic Brain Metastases After Failure of Osimertinib

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 28 (estimated)
• Sponsor: Jin Hyoung Kang · Academic / Other
• Sex: All
• Age: 20 Years
• Healthy volunteers: Not accepted

Summary

The primary objective is to evaluate the intracranial efficacy of pemetrexed/carboplatin chemotherapy and lazertinib combination therapy after osimertinib failure in EGFR-positive non-small cell lung cancer patients with brain metastasis. The primary endpoint is the incracranial objective response rate (iORR). Secondary endpoints are intracranial progression free survival, (iPFS), objective response rate (ORR), duration of response (DoR), disease control rate, (DCR), overall survival (OS), the pattern of treatment failure, intracranial salvage treatment rate, and toxicity. Patients should take lazertinib 240 mg (80 mg, 3 tablets) once a day at the same time as possible before meals. Chemotherapy will be administered on the 1st day every 3 weeks. (Pemetrexed 500mg/m2, Carboplatin AUC x 5 mg/mL.min) One cycle of treatment is defined as continuous administration for 21 days. The treatment will be applied to the all patients until documented evidence of disease progression, unacceptable toxicity, noncompliance, or withdrawal of consent, or the investigator decides to discontinue treatment, whichever comes first. If the investigator decides to reduce the dose due to an adverse reaction during the administration of lazertinib 240 mg, the dose may be reduced to 160 mg (80 mg, 2 tablets) of lazertinib. Pemetrexed and carboplatin can be administered in reduced doses according to the principles of each institution.

Detailed description

The primary objective is to evaluate the intracranial efficacy of pemetrexed/carboplatin chemotherapy and lazertinib combination therapy after osimertinib failure in EGFR-positive non-small cell lung cancer patients with brain metastasis. The primary endpoint is the incracranial objective response rate (iORR), defined as the proportion of patients achieving a complete response or partial response of intracranial lesions per RECIST v1.1 by investigator's assessments. Secondary endpoints are intracranial progression free survival, (iPFS), objective response rate (ORR), duration of response (DoR), disease control rate, (DCR), overall survival (OS), the pattern of treatment failure, intracranial salvage treatment rate, and toxicity. Intracranial objective response rate (iORR): percentage of subjects with at least one confirmed response (CR or PR or responding) in the intracranial lesion before evidence of progression in patients with brain metastases Intracranial progression free survival (iPFS): From C1D1 to the date of either disease progression of intracranial lesions or death Objective response rate (ORR): proportion of patients achieving a complete response or partial response of overall lesions Duration of response (DoR): From the first recorded response to the first recorded disease progression or death Disease control rate, (DCR): proportion of patients achieving a complete response or partial response or stable disease of overall lesions Overall survival: From C1D1 to the date of all-cause mortality Safety: Evaluated by NCI-CTCAE v5.0 Pattern of treatment failure: intracranial progression, extracranial progression, or both Intracranial salvage treatment rate: Percentage of subjects who underwent salvage treatment(surgery or radiation) due to intracranial disease progression The exploratory objective is to identify molecular profiling using next generation sequencing. Patients should take lazertinib 240 mg (80 mg, 3 tablets) once a day at the same time as possible before meals. Chemotherapy will be administered on the 1st day every 3 weeks. (Pemetrexed 500mg/m2, Carboplatin AUC x 5 mg/mL.min) One cycle of treatment is defined as continuous administration for 21 days. The treatment will be applied to the all patients until documented evidence of disease progression, unacceptable toxicity, noncompliance, or withdrawal of consent, or the investigator decides to discontinue treatment, whichever comes first. If the investigator decides to reduce the dose due to an adverse reaction during the administration of lazertinib 240 mg, the dose may be reduced to 160 mg (80 mg, 2 tablets) of lazertinib. Pemetrexed and carboplatin can be administered in reduced doses according to the principles of each institution. To prevent side effects of pemetrexed, start at least 7 days before cycle 1 daily dose of 350-1,000 μg/day of folic acid and 1000 μg/3 of vitamin B12.

Conditions

• Non-small Cell Lung Cancer

Interventions

Type	Name	Description
DRUG	Lazertinib	\- Lazertinib 240mg (3 tablets, 80mg/1tablet) once a day, oral, before disease progression
DRUG	Pemetrexed	\- Pemetrexed 500mg/m2 is administered on the 1st day every 3 weeks. One cycle of treatment is defined as continuous administration for 21 days. Pemetrexed and carboplatin can be administered in reduced doses according to the principles of each institution.
DRUG	Carboplatin	\- Carboplatin AUC x 5 mg/mL.min is administered on the 1st day every 3 weeks. One cycle of treatment is defined as continuous administration for 21 days. Pemetrexed and carboplatin can be administered in reduced doses according to the principles of each institution.

Timeline

• Start date: 2022-08-01
• Primary completion: 2023-06-01
• Completion: 2025-06-01
• First posted: 2022-07-28
• Last updated: 2022-07-28

Locations

6 sites across 1 country: South Korea