This interventional study will evaluate the effectiveness, safety, and tolerability of pembrolizumab in combination with lenvatinib in adults with metastatic non-small cell lung cancer (NSCLC) who have a confirmed RET gene rearrangement and whose disease has progressed after one or more previous systemic treatments.
Participants will receive pembrolizumab intravenously once every 3 weeks in combination with lenvatinib taken by mouth daily until disease progression, unacceptable side effects, or treatment discontinuation. Tumor response will be assessed using imaging studies according to RECIST 1.1, and participants will be monitored for treatment-related side effects, progression-free survival, and overall survival. The study will also evaluate clinical and tumor characteristics, RET rearrangement variants, and the diagnostic methods used to confirm RET-positive status.
Be able and willing to sign a written informed consent form before taking part in the study.
Be 18 years of age or older.
Have a confirmed diagnosis of metastatic non-small cell lung cancer (NSCLC), established by examination of a tumor tissue sample, with cancer that has spread to distant parts of the body.
Have a confirmed RET gene rearrangement, identified using a validated molecular test, such as next-generation sequencing (NGS), polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), or another validated method.
They have previously received treatment with lenvatinib.
They have had a severe allergic or hypersensitivity reaction to pembrolizumab, lenvatinib, any component of the study medicines, or similar medicines, including human, humanized, or mouse monoclonal antibodies or immunoglobulin medicines.
They have an active autoimmune disease.
They have cancer that has spread to the central nervous system or has caused carcinomatous meningitis. Participants with brain metastases may be eligible if the brain metastases were adequately treated with radiation therapy and/or surgery and have remained stable on imaging studies.
Single group
lenvatinib pembrolizumab
Combination productParticipants will receive pembrolizumab intravenously every 3 weeks in combination with lenvatinib, which is taken orally every day until disease progression, unacceptable side effects, or treatment is stopped.
Progression-Free Survival (PFS)
Progression-free survival (PFS) is defined as the time from randomization to the date of the first documented disease progression (PD) according to the investigator's assessment using RECIST v1.1 criteria, or to death from any cause-whichever happens first. Disease progression (PD) is recorded when the sum of diameters (SOD) of target lesions increases by at least 20% from the smallest SOD previously recorded, including the baseline. In addition to the 20% relative increase, there must also be an absolute increase in SOD of at least 5 mm.
Objective Response Rate (ORR)
The objective response rate (ORR) is calculated as the proportion of participants whose best overall response (BOR) reaches either a complete (CR) or partial (PR) response for both target and non-target lesions. A complete response (CR) is defined as the disappearance of all target and non-target lesions, with any pathological lymph nodes (whether target or non-target) shrinking to less than 10 mm in short-axis diameter. A partial response (PR) is recorded when the sum of diameters of target lesions decreases by at least 30% from baseline. Tumor burden is assessed according to modified RECIST 1.1 criteria: up to five target lesions in total are considered, with no more than two lesions per organ.
Disease Control Rate (DCR)
The disease control rate (DCR) is calculated as the proportion of participants who, according to the investigator's assessment based on RECIST v1.1 criteria, achieve the best overall response of complete response (CR), partial response (PR), or stable disease (SD). Stable disease (SD) is defined as not enough reduction in tumor burden to qualify as CR or PR, and at the same time not enough increase to qualify as disease progression (PD). A complete response (CR) is recorded when all target lesions disappear; any pathological lymph nodes must shrink to less than 10 mm in the short axis. A partial response (PR) is noted when the sum of diameters (SOD) of all target lesions decreases by at least 30% compared to the baseline SOD, without signs of a CR. Disease progression (PD) is defined as an increase in the SOD of target lesions by at least 20% compared to the smallest recorded SOD at previous time points (including baseline); in addition to the 20% relative increase, there also needs t
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