This is a Phase II single center, open-label, single arm study in patients with advanced non-small cell lung cancer (stage IV) with brain metastases. This study will be treated with combination of Pembrolizumab 200mg plus platinum doublet based on histology subtypes.
This is a Phase II single center, open-label, single arm study in patients with advanced non-small cell lung cancer (stage IV) with brain metastases. Patients will be treated with combination of Pembrolizumab 200mg plus platinum doublet based on histology subtypes. After the 4 cycles of combination phase with cytotoxic chemotherapy, maintenance phase will be followed for maximum of 35 cycles. If the disease progression is observed in CNS only which can be controlled with local treatment, systemic treatment can be continued as beyond disease progression. Non-squamous cell carcinoma: 4 cycles of pemetrexed 500mg/m2 + carboplatin AUC 5.0 + pembrolizumab 200mg every 3 weeks Followed by pemetrexed 500mg/m2 + pembrolizumab 200mg every 3 weeks up to 35 cycles Squamous cell carcinoma: 4 cycles of paclitaxel 200mg/m2 + carboplatin AUC 6.0 + pembrolizumab 200mg every 3 weeks Followed by pembrolizumab 200mg every 3 weeks up to 35 cycles
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
13
* Pemetrexed 500mg/m2 * Carboplatin AUC 5.0 * Pembrolizumab 200mg
* Paclitaxel 200mg/m2 * Caboplatin AUC 6.0 * Pembrolizumab 200mg
Samsung Medical Center
Seoul, Gangnamgu, South Korea
Intracranial Objective Response Rate
Intracranial objective response is defined as the investigator's best non-confirmed response as CR (complete response) or PR (partial response) as determined using RECIST v1.1. Subjects who do not meet these criteria, including those without a post-baseline tumor assessment, are considered non-responders. Intracranial objective response rate (iORR) is defined as the proportion of subjects who achieved an objective response among all subjects treated with the IP who had measurable disease at baseline. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of t the diameters of target lesion.
Time frame: Up to 24 months
Progression Free Survival (PFS)
PFS is defined as the period between the start date of the investigational drug and the date of the first documented disease progression or death, whichever occurs first. \- PFS (month) = (date of the first documented disease progression or death - date of the start of the investigational drug + 1) / 30.4375 Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of diameters of TLs, taking as reference the smallest sum of diameters (nadir) on study (this includes the baseline sum if that is the smallest on study), or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: The time until the date of either disease progression or the all-cause mortality from the date of IP administration. Up to 30 months
Overall Survival (OS)
Overall survival defined by date of all-cause mortality from the date of IP Administration will be calculated.
Time frame: The time until defined by date of all-cause mortality from the date of IP Administration. Up to 30 months.
Intracranial Duration of Response
The duration for intracranial response will be calculated separately to evaluate the intracranial efficacy of IP drug
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Time frame: Up to 30 months.
Intracranial Progression-free Survival
Progression free survival of intracranial disease defined by the date of disease progression of intracranial lesion from the date of IP administration will be calculated. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of diameters of TLs, taking as reference the smallest sum of diameters (nadir) on study (this includes the baseline sum if that is the smallest on study), or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: Up to 30 months.
Objective Response Rate
Objective response rate is defined as the investigator's best non-confirmed response as CR (complete response) or PR (partial response) as determined using RECIST v1.1. Subjects who do not meet these criteria, including those without a post-baseline tumor assessment, are considered non-responders. objective response rate (ORR) is defined as the proportion of subjects who achieved an objective response among all subjects treated with the IP who had measurable disease at baseline. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of t the diameters of target lesion.
Time frame: Up to 30 months.
Adverse Events
Adverse event will be evaluated using CTCAE v5.0
Time frame: from the date of informed consent signature to 30 days after last drug administration