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 (ALK-PPL)

Centro di Riferimento Oncologico - Aviano

Status and phase: Enrolling; Phase 2

Conditions: Non Small Cell Lung Cancer Metastatic; ALK Gene Mutation

Treatments: Drug: Lorlatinib

Study type: Interventional

Funder types: Other

Identifiers

NCT06378892

CRO-2023-78

Details and patient eligibility

About

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.

Full description

This is a multicentre, phase II, interventional, prospective, single arm, non-randomised study focused on ALK+ NSCLC with extracranial progression on Lorlatinib.Treatment phase include the period starting from cycle 1 day 1 visit to discontinuation of study therapy and consists of two phases: induction phase and maintenance phase. 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.

Enrollment: 45 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• 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.

Key Exclusion Criteria:

• 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.
• Concomitant use of potent CYP3A4/5 inducers.

Other inclusion/exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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45 participants in 1 patient group

Lorlatinib

Experimental group

Description:

Lorlatinib 100mg once daily. Carboplatin AUC 5 or Cisplatin 75 mg/m\^2 for an induction phase of four cycles. Pemetrexed 500 mg/m\^2 during the maintenance phase.

Treatment:

Drug: Lorlatinib