Impact of Using a GLP1 on Treatment Related Side Effects of Lung Cancer Patients Receiving Lorlatinib

Impact of Tirzepatide on Lorlatinib-Associated Weight Gain and Metabolic Derangements in Patients With Non-Small Cell Lung Cancer (NSCLC)

The proposed study seeks to address a critical gap in the management of lorlatinib-induced metabolic derangements, particularly rapid weight gain, which can adversely affect treatment adherence, dosing and ultimately patient outcomes. In this study patients with non-small cell lung cancer (NSCLC) receiving lorlatinib treatment will receive tirzepatide, a dual GIP/GLP-1 receptor agonist with demonstrated efficacy in weight reduction and metabolic improvement. This study seeks to evaluate its potential to mitigate side effects while preserving the therapeutic efficacy of lorlatinib.

Inclusion Criteria:

• Age ≥ 18 years
• Receiving lorlatinib as first-line treatment for advanced NSCLC ALK-positive, already prescribed and administered by the patient's treating oncologist as standard of care at the time of study enrollment. This study does not initiate lorlatinib therapy or assign lorlatinib dosing; participants must already be receiving lorlatinib prior to enrollment

Exclusion Criteria:

• Known hypersensitivity to GLP-1 agonists.
• Active, unstable psychiatric illness; current suicidal ideation
• Severe organ dysfunction or systemic illness.
• Anorexia nervosa
• History of pancreatitis
• Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2
• Current use of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA) or glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) [GLP-1 RA/GIP] co-agonist use within the last 90 days prior to screening
• Current anti-obesity medication use (other than GLP-1 RA) or dipeptidyl peptidase-4 (DPP4) inhibitor use or use within the last 30 days prior to screening
• Pregnant, breastfeeding or planning pregnancy