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

NCT07782359 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: IRB25-1926
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Lung Cancer

Outcome Measures

Primary Outcomes (5)

• Body weight changes

  To assess the effect of tirzepatide, on change in body weight in patients taking lorlatinib.

  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.

  1 year post treatment start

• Change in Cmax

  Determine if the peak concentration of Lorlatinib is significantly altered when co-administered with tirzepatide.

  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.

  1 year post treatment start

• Bioavailability

  Evaluate partial AUC to estimate the extent of drug absorption.

  1 year post treatment start

Secondary Outcomes (4)

• Rate of metabolic side effects

  1 year from start of treatment

• Changes in body mass composition

  1 year from start of treatment

• Changes in waist circumference

  1 year from start of treatment

• Changes in cardiometabolic markers

  1 year from start of treatment

Study Arms (1)

Tirzepatide Treatment

EXPERIMENTAL

Individuals taking with an body mass index (BMI) in obese range (BMI greater than or equal to 30) or those with a BMI greater than or equal to 27 and with cardiac risk factors will receive tirzepatide starting after study enrollment. Individuals that do not meet these BMI criteria will start tirzepatide if they experience weight gain of 5% of more during the study. Statistical analysis will include all participants that receive tirzepatide on this study.

Drug: Tirzepatide

Interventions

Tirzepatide DRUG

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.

Also known as: Monjouro, Zepbound

Tirzepatide Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: collaborator
• University of Chicago: lead

Study Sites (1)

University of Chicago Medicine Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Study Officials

• Marina Garassino

  University of Chicago

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trials Intake Intake

CONTACT

855-702-8222; cancerclinicaltrials@bsd.uchicago.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2026
• First Posted: August 24, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2030
• Last Updated: August 24, 2026

Record last verified: 2026-08

Locations

US (1)