Lorlatinib for Lung Cancer

Recruiting at 31 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Pfizer

Must be taking: Lorlatinib

Disqualifiers: Pregnancy, Breastfeeding, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

74 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial aims to continue providing lorlatinib to patients who are still benefiting from it. Lorlatinib is a medication that helps stop cancer cells from growing. The trial will also collect more safety data to better understand any side effects. Lorlatinib is used to treat non-small-cell lung cancer with ALK or ROS1 rearrangement, and it has been studied to assess its safety and effectiveness.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is lorlatinib safe for humans?

Lorlatinib is generally well tolerated, but it can cause some side effects like high cholesterol and effects on the nervous system. These side effects are usually mild to moderate and can often be managed with dose adjustments or standard treatments. ^{1 2 3 4 5}

How is the drug lorlatinib different from other treatments for lung cancer?

Lorlatinib is unique because it is a third-generation tyrosine kinase inhibitor (a type of drug that blocks certain enzymes involved in cancer cell growth) specifically targeting ALK-positive non-small cell lung cancer, and it has shown effectiveness even in the brain. It is taken orally, which can be more convenient compared to treatments that require hospital visits. ^{6 7 8 9 10}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for individuals with non-small cell lung cancer who are benefiting from ongoing Lorlatinib treatment in previous Pfizer studies. They must have good bone marrow, liver, kidney, and pancreatic function and agree to follow reproductive guidelines. Pregnant or breastfeeding women can't participate.

Inclusion Criteria

Participants must agree to follow the reproductive criteria

My bone marrow, liver, kidneys, and pancreas are functioning well.

You are currently receiving a treatment called lorlatinib in another study sponsored by Pfizer and it is helping you.

Exclusion Criteria

I am not pregnant or breastfeeding.

Any medical reason that, in the opinion of the Investigator or Sponsor, precludes the participant from inclusion in the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Continuation Treatment

Participants continue to receive lorlatinib treatment as a single agent, 100 mg orally once daily

Up to approximately 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 5 years

Treatment Details

Interventions

• Lorlatinib

Trial Overview The study continues providing Lorlatinib to patients from prior trials who still benefit from it. It aims to gather more safety data on the long-term use of Lorlatinib in treating non-small cell lung cancer.

Participant Groups

Group I: Lorlatinib Experimental Treatment 1 Intervention

Lorlatinib single agent, 100 mg (4 x 25 mg) oral tables, QD, continuously

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Findings from Research

Neurocognitive adverse events (NAEs) are common in patients receiving lorlatinib, with 60% of patients in one cohort and 49% in another experiencing these effects, particularly cognitive and mood-related issues.

Factors such as brain metastases, brain radiation, psychiatric illness, and the use of certain medications (like antiepileptics and stimulants) are associated with an increased risk of developing NAEs, suggesting that patient history and treatment context are important for managing these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors Associated With Developing Neurocognitive Adverse Events in Patients Receiving Lorlatinib After Progression on Other Targeted Therapies. Dagogo-Jack, I., Abbattista, A., Murphy, JF., et al.[2023]

Lorlatinib, a third-generation ALK tyrosine kinase inhibitor, demonstrates strong effectiveness in treating non-small cell lung cancer (NSCLC) patients with ALK mutations who have not responded to earlier treatments.

The safety profile of lorlatinib includes manageable side effects like hyperlipidemia and central nervous system issues, with few cases requiring permanent discontinuation, making it a well-tolerated option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in the Management of Adverse Events Associated with Lorlatinib. Liao, D., Zhang, J., Yan, T., et al.[2023]

Lorlatinib is a promising third-generation ALK tyrosine kinase inhibitor that effectively penetrates the blood-brain barrier and targets most resistance mutations associated with earlier ALK inhibitors, making it a strong option for treating ALK-positive non-small-cell lung cancer.

The safety profile of lorlatinib is generally favorable, with most adverse events being mild to moderate and manageable, allowing for continued treatment without significant interruptions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consensus Recommendations for Management and Counseling of Adverse Events Associated With Lorlatinib: A Guide for Healthcare Practitioners. Reed, M., Rosales, AS., Chioda, MD., et al.[2021]

Lorlatinib shows significant brain penetration and demonstrates autoinduction after multiple doses, which means its clearance increases with continued use, potentially affecting dosing strategies.

In a study involving 329 patients (54 in phase I and 275 in phase II), lorlatinib's plasma exposure increased proportionally with single doses and slightly less so with multiple doses, indicating consistent efficacy in treating ALK-positive non-small cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Lorlatinib After Single and Multiple Dosing in Patients with Anaplastic Lymphoma Kinase (ALK)-Positive Non-Small Cell Lung Cancer: Results from a Global Phase I/II Study. Chen, J., O'Gorman, MT., James, LP., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Monitoring and Managing Lorlatinib Adverse Events in the Portuguese Clinical Setting: A Position Paper. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Factors Associated With Developing Neurocognitive Adverse Events in Patients Receiving Lorlatinib After Progression on Other Targeted Therapies. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Recent Advances in the Management of Adverse Events Associated with Lorlatinib. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Consensus Recommendations for Management and Counseling of Adverse Events Associated With Lorlatinib: A Guide for Healthcare Practitioners. [2021]

5. Ireland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of lorlatinib in Asian and non-Asian patients with ALK-positive advanced non-small cell lung cancer: Subgroup analysis of a global phase 2 trial. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

The Effect of Rifampin on the Pharmacokinetics and Safety of Lorlatinib: Results of a Phase One, Open-Label, Crossover Study in Healthy Participants. [2021]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Lorlatinib for the Treatment of Adult Patients with Anaplastic Lymphoma Kinase Positive Advanced Non-Small Cell Lung Cancer in Spain. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Lorlatinib After Single and Multiple Dosing in Patients with Anaplastic Lymphoma Kinase (ALK)-Positive Non-Small Cell Lung Cancer: Results from a Global Phase I/II Study. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Evaluation of the absolute oral bioavailability of the anaplastic lymphoma kinase/c-ROS oncogene 1 kinase inhibitor lorlatinib in healthy participants. [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Lorlatinib: First Global Approval. [2021]