A Study to Evaluate 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

Prior treatment

• Presence of toxicities contraindicating the continuation of therapy with Lorlatinib.
• Concomitant use of potent CYP3A4/5 inducers.
  • Other inclusion/exclusion criteria may apply.

Other illness

• 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.

Other

• Patients deemed unsuitable by the investigator for treatment of chemo-Lorlatinib combination.

• 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.
• Patients must have measurable disease according to RECIST 1.1 by computed tomography (CT) and magnetic resonance imaging (MRI).
• Radiologically confirmed multiple extracranial progression on Lorlatinib without progression in the central nervous system (CNS) defined as absence of CNS metastasis or CNS metastasis stable on Lorlatinib and/or stereotactic brain irradiation (SBRT).
• Adequate organ function (kidney, bone marrow and liver).
• Estimated life expectancy of at least 3 months irrespective of the diagnosis of ALK+ NSCLC.
• For women of childbearing potential and males with partners of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \< 1% per year during the treatment period and for at least 6 months after the last dose of study drugs.