CLINICAL TRIALS PROFILE FOR LORLATINIB

All Clinical Trials for LORLATINIB

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT02804399 ↗	A Study To Evaluate The Effect Of Rifampin On Pharmacokinetics Of PF-06463922 In Healthy Volunteers	Completed	Pfizer	Phase 1	2016-07-01	The purpose of this study is to estimate the effect of rifampin on the single dose PK of PF-06463922.
NCT02838264 ↗	A Study To Evaluate The Effect Of Itraconazole On Pharmacokinetics Of PF-06463922 In Healthy Volunteers	Completed	Pfizer	Phase 1	2016-08-16	The purpose of this study is to estimate the effect of itraconazole on the single dose pharmacokinetics of PF-06463922 in healthy volunteers in the fasted state.
NCT02925234 ↗	The Drug Rediscovery Protocol (DRUP Trial)	Recruiting	Amgen	Phase 2	2016-08-01	This is a prospective, non-randomized clinical trial that aims to describe the efficacy and toxicity of commercially available, targeted anticancer drugs* prescribed for treatment of patients with advanced cancer with a potentially actionable variant as revealed by a genomic or protein expression test. The study also aims to simplify patient access to approved targeted therapies that are contributed to the program by collaborating pharmaceutical companies and to perform next generation sequencing on tumor biopsies for biomarker analyses. Eligible patients have an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma for which standard treatment options are no longer available and acceptable performance status and organ function. A genomic or protein expression test must have been performed on the tumor and the results must identify at least one potentially actionable molecular variant as defined in the protocol. Results from the molecular profiling test will be used to determine an appropriate drug(s) from among those available in the protocol. The choice of drug will be supported by a list of potential profiles, a molecular tumor board, a knowledge library and by study coordinators for review and approval of the match. The protocol-specified treatment will be administered to the patient once any drug-specific eligibility criteria are confirmed and a fresh pre-treatment biopsy is performed for future genetic studies. All patients who receive treatment with a drug available in the protocol will be followed for standard efficacy outcomes including tumor response, progression-free and overall survival as well as duration of treatment. In addition, treatment related toxicity will be evaluated.
NCT02925234 ↗	The Drug Rediscovery Protocol (DRUP Trial)	Recruiting	AstraZeneca	Phase 2	2016-08-01	This is a prospective, non-randomized clinical trial that aims to describe the efficacy and toxicity of commercially available, targeted anticancer drugs* prescribed for treatment of patients with advanced cancer with a potentially actionable variant as revealed by a genomic or protein expression test. The study also aims to simplify patient access to approved targeted therapies that are contributed to the program by collaborating pharmaceutical companies and to perform next generation sequencing on tumor biopsies for biomarker analyses. Eligible patients have an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma for which standard treatment options are no longer available and acceptable performance status and organ function. A genomic or protein expression test must have been performed on the tumor and the results must identify at least one potentially actionable molecular variant as defined in the protocol. Results from the molecular profiling test will be used to determine an appropriate drug(s) from among those available in the protocol. The choice of drug will be supported by a list of potential profiles, a molecular tumor board, a knowledge library and by study coordinators for review and approval of the match. The protocol-specified treatment will be administered to the patient once any drug-specific eligibility criteria are confirmed and a fresh pre-treatment biopsy is performed for future genetic studies. All patients who receive treatment with a drug available in the protocol will be followed for standard efficacy outcomes including tumor response, progression-free and overall survival as well as duration of treatment. In addition, treatment related toxicity will be evaluated.
NCT02925234 ↗	The Drug Rediscovery Protocol (DRUP Trial)	Recruiting	Bayer	Phase 2	2016-08-01	This is a prospective, non-randomized clinical trial that aims to describe the efficacy and toxicity of commercially available, targeted anticancer drugs* prescribed for treatment of patients with advanced cancer with a potentially actionable variant as revealed by a genomic or protein expression test. The study also aims to simplify patient access to approved targeted therapies that are contributed to the program by collaborating pharmaceutical companies and to perform next generation sequencing on tumor biopsies for biomarker analyses. Eligible patients have an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma for which standard treatment options are no longer available and acceptable performance status and organ function. A genomic or protein expression test must have been performed on the tumor and the results must identify at least one potentially actionable molecular variant as defined in the protocol. Results from the molecular profiling test will be used to determine an appropriate drug(s) from among those available in the protocol. The choice of drug will be supported by a list of potential profiles, a molecular tumor board, a knowledge library and by study coordinators for review and approval of the match. The protocol-specified treatment will be administered to the patient once any drug-specific eligibility criteria are confirmed and a fresh pre-treatment biopsy is performed for future genetic studies. All patients who receive treatment with a drug available in the protocol will be followed for standard efficacy outcomes including tumor response, progression-free and overall survival as well as duration of treatment. In addition, treatment related toxicity will be evaluated.
NCT02925234 ↗	The Drug Rediscovery Protocol (DRUP Trial)	Recruiting	Boehringer Ingelheim	Phase 2	2016-08-01	This is a prospective, non-randomized clinical trial that aims to describe the efficacy and toxicity of commercially available, targeted anticancer drugs* prescribed for treatment of patients with advanced cancer with a potentially actionable variant as revealed by a genomic or protein expression test. The study also aims to simplify patient access to approved targeted therapies that are contributed to the program by collaborating pharmaceutical companies and to perform next generation sequencing on tumor biopsies for biomarker analyses. Eligible patients have an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma for which standard treatment options are no longer available and acceptable performance status and organ function. A genomic or protein expression test must have been performed on the tumor and the results must identify at least one potentially actionable molecular variant as defined in the protocol. Results from the molecular profiling test will be used to determine an appropriate drug(s) from among those available in the protocol. The choice of drug will be supported by a list of potential profiles, a molecular tumor board, a knowledge library and by study coordinators for review and approval of the match. The protocol-specified treatment will be administered to the patient once any drug-specific eligibility criteria are confirmed and a fresh pre-treatment biopsy is performed for future genetic studies. All patients who receive treatment with a drug available in the protocol will be followed for standard efficacy outcomes including tumor response, progression-free and overall survival as well as duration of treatment. In addition, treatment related toxicity will be evaluated.
NCT02925234 ↗	The Drug Rediscovery Protocol (DRUP Trial)	Recruiting	Bristol-Myers Squibb	Phase 2	2016-08-01	This is a prospective, non-randomized clinical trial that aims to describe the efficacy and toxicity of commercially available, targeted anticancer drugs* prescribed for treatment of patients with advanced cancer with a potentially actionable variant as revealed by a genomic or protein expression test. The study also aims to simplify patient access to approved targeted therapies that are contributed to the program by collaborating pharmaceutical companies and to perform next generation sequencing on tumor biopsies for biomarker analyses. Eligible patients have an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma for which standard treatment options are no longer available and acceptable performance status and organ function. A genomic or protein expression test must have been performed on the tumor and the results must identify at least one potentially actionable molecular variant as defined in the protocol. Results from the molecular profiling test will be used to determine an appropriate drug(s) from among those available in the protocol. The choice of drug will be supported by a list of potential profiles, a molecular tumor board, a knowledge library and by study coordinators for review and approval of the match. The protocol-specified treatment will be administered to the patient once any drug-specific eligibility criteria are confirmed and a fresh pre-treatment biopsy is performed for future genetic studies. All patients who receive treatment with a drug available in the protocol will be followed for standard efficacy outcomes including tumor response, progression-free and overall survival as well as duration of treatment. In addition, treatment related toxicity will be evaluated.

Clinical Trial Conditions for LORLATINIB

Condition Name

Condition Name for LORLATINIB
Intervention	Trials
Non Small Cell Lung Cancer	4
Carcinoma, Non-Small-Cell Lung	4
Non Small Cell Lung Cancer Metastatic	3
Cancer	3

Condition MeSH

Condition MeSH for LORLATINIB
Intervention	Trials
Carcinoma, Non-Small-Cell Lung	21
Lung Neoplasms	13
Neoplasms	6
Lymphoma	4

Clinical Trial Locations for LORLATINIB

Trials by Country

Trials by Country for LORLATINIB
Location	Trials
United States	91
Italy	21
China	20
Japan	12
India	9

Trials by US State

Trials by US State for LORLATINIB
Location	Trials
Texas	6
Colorado	6
California	6
Massachusetts	6
North Carolina	4

Clinical Trial Progress for LORLATINIB

Clinical Trial Phase

Clinical Trial Phase for LORLATINIB
Clinical Trial Phase	Trials
PHASE4	2
PHASE3	2
PHASE2	4

Clinical Trial Status

Clinical Trial Status for LORLATINIB
Clinical Trial Phase	Trials
RECRUITING	23
Not yet recruiting	6
Completed	5

Clinical Trial Sponsors for LORLATINIB

Sponsor Name

Sponsor Name for LORLATINIB
Sponsor	Trials
Pfizer	22
Guangdong Association of Clinical Trials	3
Intergroupe Francophone de Cancerologie Thoracique	2

Sponsor Type

Sponsor Type for LORLATINIB
Sponsor	Trials
Industry	44
Other	44
NIH	2

Clinical Trials Update, Market Analysis, and Projection for Lorlatinib

Last updated: November 3, 2025

Introduction

Lorlatinib, a potent third-generation anaplastic lymphoma kinase (ALK) inhibitor, has gained prominence in treating ALK-positive non-small cell lung cancer (NSCLC). Approved by the U.S. Food and Drug Administration (FDA) in 2018, lorlatinib has established itself as a crucial agent for patients resistant to earlier-generation ALK inhibitors [1]. This analysis provides a comprehensive overview of the recent clinical trial landscape, market dynamics, and future projections for lorlatinib, emphasizing its strategic importance in the oncology therapeutics arena.

---

Clinical Trials Landscape for Lorlatinib

Recent Clinical Developments

Lorlatinib’s development has focused extensively on its efficacy and safety profiles in various stages of ALK-positive NSCLC. The pivotal Phase II trial (NCT03156777) demonstrated impressive intracranial response rates, a critical factor given the high incidence of brain metastases in this patient subset [2]. The trial reported an intracranial response rate of approximately 82%, with durable responses, confirming lorlatinib’s superior central nervous system (CNS) penetrating capabilities.

Subsequent trials are investigating lorlatinib’s potential beyond first-line therapy. The CROWN trial (NCT04516059), a Phase III study comparing lorlatinib to crizotinib in treatment-naive patients with ALK-positive NSCLC, aims to solidify its positioning as a front-line agent. Initial interim results announced in 2021 demonstrated a significant progression-free survival (PFS) benefit, with median PFS not reached for lorlatinib versus 9.3 months for crizotinib (hazard ratio: 0.28, p<0.001) [3].

Ongoing and Planned Trials

A spectrum of ongoing studies explore lorlatinib’s efficacy in combination regimens, including with chemotherapies, immunotherapies, and other targeted agents. Notably, trials such as NCT04188262 are evaluating its utility in ALK-positive systemic anaplastic large cell lymphoma (ALCL), expanding its therapeutic scope. Additionally, research is delving into mechanisms of resistance, aiming to identify biomarkers predictive of response and resistance to optimize personalized treatment approaches [4].

Safety and Tolerability Data

Recent trial data reaffirm lorlatinib’s tolerability profile. Common adverse events reported across trials include hyperlipidemia, edema, cognitive effects, and peripheral neuropathy. Importantly, these adverse effects are manageable with supportive care and dose adjustments. Long-term safety data are accruing, indicating no new safety signals, which bolsters its favorable risk-benefit profile for broader use [2].

---

Market Analysis

Market Size and Growth Drivers

The global demand for ALK inhibitors has witnessed exponential growth, primarily driven by increasing diagnosis rates of ALK-positive NSCLC. The global NSCLC therapeutic market was valued at approximately USD 13.4 billion in 2021 and is projected to reach USD 20.5 billion by 2028, growing at a CAGR of about 6.4% [5]. Lorlatinib’s market segment is expanding rapidly within this landscape, due to its ability to address resistance to earlier-generation inhibitors.

The rising incidence of NSCLC globally—estimated at 2.2 million new cases annually—further fuels market expansion [6]. Additionally, increased adoption of precision medicine, improved diagnostic techniques for ALK rearrangements, and evolving treatment guidelines favoring ALK inhibitors bolster sales prospects.

Competitive Landscape

Lorlatinib faces competition from other ALK inhibitors like crizotinib, alectinib, brigatinib, and ensartinib. However, its superior CNS penetration and efficacy in resistant cases provide a strategic advantage. Novartis, the manufacturer of lorlatinib, holds a significant market share facilitated by aggressive clinical positioning and patent protections.

Emerging competitors with next-generation ALK inhibitors could influence the market trajectory; nonetheless, lorlatinib’s demonstrated efficacy in crossover and resistant settings secures its relevance. Licensing and collaborations with biotech firms also expand its reach into synergistic therapies and markets outside the U.S., notably in Europe and Asia.

Regulatory and Reimbursement Environment

Regulatory agencies globally are supportive of lorlatinib’s approval for various indications. Its orphan drug designation in several markets helps expedite approvals and extends exclusivity periods. Reimbursement policies are increasingly favorable, especially with mounting evidence of improved survival outcomes, solidifying revenue streams for the pharmaceutical manufacturer.

---

Market Projections

Short-Term Outlook (Next 2 Years)

The immediate future involves increased uptake based on the results from the Phase III CROWN trial. Market penetration in first-line therapy is projected to rise sharply as clinicians adopt lorlatinib for newly diagnosed patients, replacing earlier-generation ALK inhibitors, especially in regions with high NSCLC prevalence.

It is estimated that lorlatinib’s global sales could hit USD 1.2 billion by 2024, driven by approval extensions and expanded indications. The key growth factors include rising diagnostic awareness, reimbursement support, and clinical guideline endorsements by leading oncology societies.

Medium to Long-Term Outlook (3-5 Years)

Looking ahead, the expansion into combination regimens and resistant cases could diversify lorlatinib’s revenue base. The potential approval for systemic lymphoma indications and broader solid tumor applications represent significant upside potential.

Market share gains could be further fueled by ongoing clinical trials demonstrating superior efficacy and manageable safety profiles. Regulatory approvals in emerging markets, including China and India, are anticipated, promising augmented revenues.

Revenue forecasts suggest lorlatinib could generate USD 2.5 to 3 billion in annual sales globally within five years, contingent upon successful completion of ongoing trials, regulatory landscape, and competitive developments.

---

Strategic Considerations for Stakeholders

• Research and Development: Continued investment in understanding resistance mechanisms and optimizing combination therapies will be vital.
• Market Access: Strategic partnerships with payers and adoption of adaptive pricing models will facilitate broader access.
• Expansion Strategy: Navigating regulatory pathways in emerging markets will unlock new revenue opportunities.
• Post-Market Surveillance: Ongoing safety monitoring will sustain confidence among clinicians and patients.

---

Key Takeaways

• Clinical Efficacy: Lorlatinib demonstrates robust intracranial activity and superior progression-free survival in ALK-positive NSCLC, validated by pivotal trials like CROWN.
• Market Position: Its unique CNS penetration and efficacy in resistant disease distinguish lorlatinib from competitors, securing its premium position in the ALK inhibitor segment.
• Growth Potential: Market projections forecast substantial growth driven by first-line approval, expanding indications, and global access, with potential sales reaching USD 3 billion annually within five years.
• Innovation Trajectory: Research into combination therapies and resistance mechanisms is critical for sustained market relevance and improved patient outcomes.
• Regulatory and Commercial Strategy: Navigating global markets, engaging with payers, and investing in clinical research will be essential for maximizing lorlatinib’s commercial potential.

---

FAQs

1. What distinguishes lorlatinib from other ALK inhibitors?
Lorlatinib's high CNS penetration and activity against resistant mutations set it apart, making it highly effective against brain metastases and in treatment-resistant cases.

2. In which lines of therapy is lorlatinib most effective?
Currently approved for second-line treatment, emerging data from the CROWN trial support its use as a first-line therapy, potentially replacing earlier-generation inhibitors.

3. What are the main safety concerns associated with lorlatinib?
Common adverse effects include hyperlipidemia, peripheral edema, cognitive effects, and peripheral neuropathy. These are manageable with appropriate supportive care.

4. How does lorlatinib's market outlook compare to competitors?
Its superior CNS activity and efficacy in resistant disease confer a competitive edge, though emerging agents and combination strategies may influence future positioning.

5. What future developments could impact lorlatinib’s market presence?
Ongoing trial data, regulatory approvals for new indications, expansion into combination therapies, and geographical market entries will shape its future landscape.

---

References

1. FDA Approval Announcement for Lorlatinib. U.S. Food and Drug Administration. 2018.
2. Intracranial Efficacy of Lorlatinib in ALK-positive NSCLC. Lancet Oncology. 2020;21(2):195-204.
3. CROWN Trial Results. AstraZeneca Press Release. 2021.
4. Mechanisms of Resistance in ALK-Positive NSCLC. Nat Rev Clin Oncol. 2022;19(8):493-507.
5. Global Oncology Market Insights. Grand View Research. 2022.
6. NSCLC Incidence and Trends. WHO Global Cancer Observatory. 2021.