Lorlatinib for Lung Cancer

Not currently recruiting at 35 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to continue providing the lung cancer treatment lorlatinib to participants who still benefit from it. The focus is on collecting additional data about lorlatinib's safety to better understand its effects on patients. It suits those who participated in previous Pfizer lorlatinib studies and are experiencing positive results. Participants must have stable bodily functions, such as bone marrow and liver health, to join. As a Phase 4 trial, this study involves an FDA-approved treatment and seeks to understand how lorlatinib benefits more patients.

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.

What is the safety track record for Lorlatinib?

Research has shown that lorlatinib is generally well-tolerated by people with lung cancer. Studies have found that lorlatinib effectively treats certain types of lung cancer, including cases where the cancer has spread to the brain. Importantly, recent studies have not identified any new safety concerns.

Some patients have experienced side effects such as swelling, weight gain, and mood changes. However, these side effects can be managed, and the benefits of the treatment often outweigh these challenges. Long-term safety data suggests that lorlatinib remains a safe option for many patients, which is why ongoing treatments continue to use it. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Lorlatinib is unique because it specifically targets an abnormal protein that drives cancer cell growth in some lung cancers, called ALK (anaplastic lymphoma kinase). Unlike existing treatments, which may include chemotherapy or earlier-generation ALK inhibitors like crizotinib, lorlatinib is a more advanced ALK inhibitor designed to overcome resistance seen with earlier drugs. Researchers are excited because lorlatinib can cross the blood-brain barrier, potentially offering better control of brain metastases, a common complication in lung cancer patients. This combination of targeted action and the ability to address brain metastases makes lorlatinib a promising option for those with ALK-positive lung cancer.

What is the effectiveness track record for Lorlatinib in treating lung cancer?

Research has shown that lorlatinib, the treatment under study in this trial, effectively treats ALK-positive lung cancer. In studies, 60% of patients taking lorlatinib survived five years without cancer progression. This treatment boasts the longest reported period without cancer growth or spread. Lorlatinib also achieved a five-year overall survival rate of 76%, indicating that most patients remained alive after five years. It has proven more effective than crizotinib, another treatment, making it a strong option for managing this type of lung cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38819031/

5-Year Outcomes From the Phase III CROWN Study Conclusion: After 5 years of follow-up, median PFS has yet to be reached in the lorlatinib group, corresponding to the longest PFS ever reported ...

2. cancer.gov cancer.gov/news-events/cancer-currents-blog/2024/lorlatinib-alk-positive-lung-cancer-initial-treatment

Lorlatinib Slows Growth of ALK-Positive Lung Cancers ... After 5 years of follow-up data, the investigators found, 60% of the participants in the lorlatinib group were alive without the disease having ...

3. jto.org jto.org/article/S1556-0864(24)02484-5/fulltext

Final Overall Survival and Long-Term Safety of Lorlatinib in ... At a median follow-up of 72.7 months, the median OS was NR with lorlatinib with a five-year OS probability of 76% in patients with treatment-naïve, advanced, ...

4. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1577607/full

Real-world analysis of the efficacy and safety of lorlatinib in ... Lorlatinib demonstrates strong efficacy and manageable safety, especially in first-line treatment of advanced ALK-positive NSCLC, supporting its role as an ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.24.00581

Lorlatinib Versus Crizotinib in Patients With Advanced ALK ... After 5 years of follow-up, lorlatinib continued to show superior efficacy over crizotinib in patients with advanced ALK-positive non–small cell ...

6. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2025.43.16_suppl.e20659

Real-life efficacy and safety data of lorlatinib treatment in ... Lorlatinib has shown clinical activity in patients with advanced ROS1-positive NSCLC, including those with CNS metastases and those previously treated with ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1525730424000792

Updated Efficacy and Safety of Lorlatinib in a Phase 2 ... The long-term data confirm robust overall and intracranial clinical activity of lorlatinib, with no new safety signals emerging. These results support using ...

8. lorbrena.pfizerpro.com lorbrena.pfizerpro.com/

LORBRENA® (lorlatinib) Official HCP Website | Safety Info Learn more about LORBRENA®, an Rx option for patients with ALK-positive metastatic non-small cell lung cancer (NSCLC). See risks and benefits.

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39581380/

Final Overall Survival and Long-Term Safety of Lorlatinib in ... We present the overall survival (OS) and long-term safety of lorlatinib in patients with advanced ALK-positive NSCLC from the final analyses of the pivotal ...