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

August 20, 2026 updated by: University of Chicago

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tirzepatide Treatment

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
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.
Other Names:
  • Monjouro, Zepbound

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Body weight changes
Time Frame: 1 year post treatment start
To assess the effect of tirzepatide, on change in body weight in patients taking lorlatinib.
1 year post treatment start
Lipid changes
Time Frame: 1 year post treatment start
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
Time Frame: 1 year post treatment start
Determine if the peak concentration of Lorlatinib is significantly altered when co-administered with tirzepatide.
1 year post treatment start
Change in Tmax
Time Frame: 1 year post treatment start
Assess if the time to peak concentration is delayed due to tirzepatide's effect on gastric emptying.
1 year post treatment start
Bioavailability
Time Frame: 1 year post treatment start
Evaluate partial AUC to estimate the extent of drug absorption.
1 year post treatment start

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of metabolic side effects
Time Frame: 1 year from start of treatment
Number of Common Terminology Criteria for Adverse Events (CTCAE) Grade 1-3 metabolic side effects
1 year from start of treatment
Changes in body mass composition
Time Frame: 1 year from start of treatment
Changes in body mass will be measured using Bioelectrical Impedance Analysis (BIA).
1 year from start of treatment
Changes in waist circumference
Time Frame: 1 year from start of treatment
1 year from start of treatment
Changes in cardiometabolic markers
Time Frame: 1 year from start of treatment
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))
1 year from start of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Chicago

Collaborators

Pfizer

Investigators

  • Principal Investigator: Marina Garassino, University of Chicago

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 1, 2026

Primary Completion (Estimated)

June 1, 2030

Study Completion (Estimated)

June 1, 2030

Study Registration Dates

First Submitted

May 7, 2026

First Submitted That Met QC Criteria

August 20, 2026

First Posted (Actual)

August 24, 2026

Study Record Updates

Last Update Posted (Actual)

August 24, 2026

Last Update Submitted That Met QC Criteria

August 20, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB25-1926

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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