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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Participants will receive tirzepatide with weekly subcutaneous injections at 2.5 mg, following a structured dose escalation protocol over 20 weeks to reach the target dose of 15 mg per week or the maximum tolerated dose.
University of Chicago Medicine Comprehensive Cancer Center
Chicago, Illinois, United States
Body weight changes
To assess the effect of tirzepatide, on change in body weight in patients taking lorlatinib.
Time frame: 1 year post treatment start
Lipid changes
To assess the effect of tirzepatide on change in lipid profile High-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, triglycerides) at 52 weeks compared to baseline.
Time frame: 1 year post treatment start
Change in Cmax
Determine if the peak concentration of Lorlatinib is significantly altered when co-administered with tirzepatide.
Time frame: 1 year post treatment start
Change in Tmax
Assess if the time to peak concentration is delayed due to tirzepatide's effect on gastric emptying.
Time frame: 1 year post treatment start
Bioavailability
Evaluate partial AUC to estimate the extent of drug absorption.
Time frame: 1 year post treatment start
Rate of metabolic side effects
Number of Common Terminology Criteria for Adverse Events (CTCAE) Grade 1-3 metabolic side effects
Time frame: 1 year from start of treatment
Changes in body mass composition
Changes in body mass will be measured using Bioelectrical Impedance Analysis (BIA).
Time frame: 1 year from start of treatment
Changes in waist circumference
Time frame: 1 year from start of treatment
Changes in cardiometabolic markers
The number of participants that experience a change in cardiometabolic markers will be reported. This includes changes in blood tests for any of the following: Hemoglobin A1c (HbA1c), insulin, glucose, Apolipoprotein B (ApoB), homocysteine, C-reactive protein (CRP), and lipoprotein(a) (Lp(a))
Time frame: 1 year from start of treatment
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