This study aims to evaluate the activity and safety of the combination of platinum-pemetrexed based chemotherapy plus Lorlatinib in ALK positive Non-Small Cell Lung Cancer (NSCLC) with exclusively extracranial disease progression on Lorlatinib. Platinum-pemetrexed based chemotherapy plus Lorlatinib will be administered for an induction phase of four cycles. Subsequently, patients with response or stability of disease at radiological assessment will start the maintenance phase with pemetrexed-Lorlatinib in 21-day cycles until progression, unacceptable toxicity, death, or withdrawal of consent.
Histologically or cytologically confirmed diagnosis of stage IV ALK positive NSCLC.
Patients must be in progression extracranially on Lorlatinib; Lorlatinib may be in first- or further-line, without limitations regarding previously received therapies.
Age at the time of signing the informed consent at least 18 years.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
Known hypersensitivity reaction to one of the compounds or substances used in this protocol.
Diagnosis of any secondary malignancy within the last 3 years except for: adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, definitively treated nonmetastatic prostate cancer or patients with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy.
Patients deemed unsuitable by the investigator for treatment of chemo-Lorlatinib combination.
Presence of toxicities contraindicating the continuation of therapy with Lorlatinib.
Single group
Lorlatinib
DrugPlatinum-pemetrexed based chemotherapy plus Lorlatinib will be administered for an induction phase of four cycles. The choice between Carboplatin or Cisplatin is entrusted to the clinician. Subsequently, patients with response or stability of disease at radiological assessment will start the maintenance phase with pemetrexed-Lorlatinib in 21-day cycles until progression, unacceptable toxicity, death, or withdrawal of consent.
Compare Progression Free Survival between patients treated with Pemetrexed (PT)/pem-based chemotherapy plus Lorlatinib after Lorlatinib versus retrospective data of 3,2 months for patients treated with PT/pem-based chemotherapy after Lorlatinib.
PFS defined as the time from study enrollment to the first documented disease progression or death due to any cause, whichever occurs first.
Intracranial Progression Free Survival (PFS) in patients treated with PT/pem-based chemotherapy plus Lorlatinib after Lorlatinib.
Intracranial PFS defined as time from study enrollment until CNS disease progression or death from any cause.
Overall survival (OS) in patients treated with PT/pem-based chemotherapy plus Lorlatinib after Lorlatinib progression
OS is defined as the time from study enrollment until death from any cause.
Describe the safety of PT/pem-based chemotherapy plus Lorlatinib combination
Frequency and severity of adverse events graded according to the CTCAE version 5.0.
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