CLINICAL TRIALS PROFILE FOR LORBRENA

All Clinical Trials for Lorbrena

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT03737994 ↗	Targeted Treatment for ALK Positive Patients Who Have Previously Been Treated for Non-squamous Non-small Cell Lung Cancer	Active, not recruiting	NRG Oncology	Phase 2	2019-04-01	This National Cancer Institute (NCI)-NRG ALK Protocol phase II trial studies how well a combination of different biomarker/ALK inhibitors work in treating patients with stage IV ALK positive non-squamous non-small cell lung cancer. Lorlatinib, ceritinib, alectinib, brigatinib, ensartinib, and crizotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as pemetrexed, cisplatin, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether a combination of biomarker/ALK inhibitors or chemotherapy may work better in treating patients with ALK positive non-squamous non-small cell lung cancer.
NCT03737994 ↗	Targeted Treatment for ALK Positive Patients Who Have Previously Been Treated for Non-squamous Non-small Cell Lung Cancer	Active, not recruiting	National Cancer Institute (NCI)	Phase 2	2019-04-01	This National Cancer Institute (NCI)-NRG ALK Protocol phase II trial studies how well a combination of different biomarker/ALK inhibitors work in treating patients with stage IV ALK positive non-squamous non-small cell lung cancer. Lorlatinib, ceritinib, alectinib, brigatinib, ensartinib, and crizotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as pemetrexed, cisplatin, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether a combination of biomarker/ALK inhibitors or chemotherapy may work better in treating patients with ALK positive non-squamous non-small cell lung cancer.
NCT03878524 ↗	Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial	Recruiting	Oregon Health and Science University	Phase 1	2020-04-01	This phase Ib trial determines if samples from a patient's cancer can be tested to find combinations of drugs that provide clinical benefit for the kind of cancer the patient has. This study is also being done to understand why cancer drugs can stop working and how different cancers in different people respond to different types of therapy.
NCT03878524 ↗	Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial	Recruiting	Prospect Creek Foundation	Phase 1	2020-04-01	This phase Ib trial determines if samples from a patient's cancer can be tested to find combinations of drugs that provide clinical benefit for the kind of cancer the patient has. This study is also being done to understand why cancer drugs can stop working and how different cancers in different people respond to different types of therapy.

Clinical Trial Conditions for Lorbrena

Condition Name

Condition Name for Lorbrena
Intervention	Trials
Lung Cancer	2
Primary Myelofibrosis	1
Severe Hepatic Impairment	1
Anaplastic Lymphoma Kinase Gene Translocation	1

Condition MeSH

Condition MeSH for Lorbrena
Intervention	Trials
Lung Neoplasms	4
Carcinoma, Non-Small-Cell Lung	3
Lymphoma	2
Hematologic Neoplasms	1

Clinical Trial Locations for Lorbrena

Trials by Country

Trials by Country for Lorbrena
Location	Trials
United States	45
China	1

Trials by US State

Trials by US State for Lorbrena
Location	Trials
Tennessee	2
Oregon	2
North Carolina	2
Massachusetts	2
Colorado	2

Clinical Trial Progress for Lorbrena

Clinical Trial Phase

Clinical Trial Phase for Lorbrena
Clinical Trial Phase	Trials
Phase 2	3
Phase 1/Phase 2	1
Phase 1	2

Clinical Trial Status

Clinical Trial Status for Lorbrena
Clinical Trial Phase	Trials
Recruiting	3
Withdrawn	1
Active, not recruiting	1

Clinical Trial Sponsors for Lorbrena

Sponsor Name

Sponsor Name for Lorbrena
Sponsor	Trials
Pfizer	3
National Cancer Institute (NCI)	1
Oregon Health and Science University	1

Sponsor Type

Sponsor Type for Lorbrena
Sponsor	Trials
Other	7
Industry	4
NIH	1

Lorbrena: A Breakthrough in ALK-Positive Non-Small Cell Lung Cancer Treatment

Introduction to Lorbrena

Lorbrena, also known as lorlatinib, is a third-generation anaplastic lymphoma kinase (ALK) inhibitor developed by Pfizer. It has been making significant waves in the treatment of ALK-positive non-small cell lung cancer (NSCLC), particularly in the first-line and subsequent treatment settings.

Clinical Trial Results

Phase 3 CROWN Trial

The pivotal Phase 3 CROWN trial has been instrumental in establishing Lorbrena's efficacy. This trial compared Lorbrena with crizotinib, a first-generation ALK inhibitor, in patients with newly diagnosed ALK-positive NSCLC. The results were striking:

• Progression-Free Survival (PFS): Lorbrena reduced the risk of disease progression or death by 72% compared to crizotinib, with a hazard ratio of 0.28 (95% CI, 0.19-0.41; P < .0001)[1][4][5].
• Five-Year Outcomes: At five years, 60% of patients on Lorbrena had not experienced tumor growth, a significant improvement over crizotinib, which had an 8% five-year progression-free survival rate[2][4].
• Brain Metastases: Lorbrena showed exceptional efficacy in patients with brain metastases, shrinking tumors in 82% of patients, compared to 23% with crizotinib. It also extended the time to central nervous system progression by 93% over crizotinib[5].

Additional Clinical Data

• Overall Response Rate: In the CROWN trial, 76% of patients had their tumors shrink or disappear while taking Lorbrena, with 3% achieving a complete response[4].
• Previously Treated Patients: In a separate trial involving 215 previously treated patients, nearly half of the patients had their tumors shrink or disappear with Lorbrena. For patients with measurable brain tumors, 60% saw their brain tumors shrink or disappear, with responses lasting a median of 20 months[4].

FDA Approval and Regulatory Status

Lorbrena has received significant regulatory approvals:

• First-Line Treatment: The FDA expanded Lorbrena’s use to include first-line treatment for ALK-positive NSCLC, converting its conditional approval for previously treated cases into a full approval[5].
• Health Canada Approval: Health Canada authorized Lorbrena for the treatment of adult patients with ALK-positive metastatic NSCLC whose disease has progressed on crizotinib and at least one other ALK inhibitor, or those whose disease has progressed on ceritinib or alectinib[3].

Market Analysis and Projections

Sales Projections

Pfizer has ambitious sales targets for Lorbrena, driven by its promising clinical trial results:

• Annual Sales: Lorbrena is projected to generate over $1 billion in annual sales by 2030, a significant increase from its $164 million in the first quarter of 2024, which represented a 46% year-over-year increase[2].
• Market Penetration: Pfizer is focusing on strategic markets, including China, where up to 7% of NSCLC patients are ALK-positive. This focus, combined with increased uptake and longer treatment durations, is expected to drive growth[2].

Competitive Landscape

Lorbrena operates in a crowded but niche market dominated by other ALK inhibitors:

• Competitors: Novartis’s Alecensa, Takeda’s Alunbrig, and Roche’s Alecensa are key competitors. However, Lorbrena’s efficacy data, particularly its ability to penetrate the blood-brain barrier and treat brain metastases, sets it apart[5].
• Market Share: Despite the competition, Lorbrena’s strong clinical data and Pfizer’s strategic marketing efforts are expected to secure a significant market share. For example, Roche’s Alecensa generated CHF 1.16 billion ($1.26 billion) in sales in 2020, indicating the potential for substantial revenue in this niche market[5].

Safety and Adverse Events

While Lorbrena has shown remarkable efficacy, it is not without side effects:

• Common Adverse Events: Edema, weight gain, peripheral neuropathy, cognitive effects, diarrhea, dyspnea, and hypertriglyceridemia are among the most common adverse events. Treatment discontinuation due to adverse events occurred in 6.7% of patients[1][5].
• Brain-Penetrating Side Effects: The drug's ability to penetrate the blood-brain barrier also comes with unique side effects such as cognition and mood changes, which are typically mild and reversible with dose interruption[5].

Strategic Importance for Pfizer

Lorbrena is a crucial component of Pfizer’s oncology portfolio:

• Revenue Growth: As Pfizer faces declining revenues from its COVID-19 products, Lorbrena’s growth is vital. Pfizer aims to have at least eight blockbuster cancer drugs by 2030, up from its current five, with Lorbrena playing a central role in this strategy[2].
• Acquisitions and Restructuring: Pfizer’s acquisition of cancer drugmaker Seagen for $43 billion and its internal restructuring efforts underscore its commitment to cancer treatments and the importance of Lorbrena in its portfolio[2].

Key Takeaways

• Clinical Efficacy: Lorbrena has demonstrated significant improvements in progression-free survival and overall response rates compared to earlier ALK inhibitors.
• Market Potential: With projected annual sales of over $1 billion by 2030, Lorbrena is poised to be a major player in the ALK-positive NSCLC market.
• Safety Profile: While effective, Lorbrena comes with a range of adverse events, including unique cognitive and mood changes due to its brain-penetrating ability.
• Strategic Importance: Lorbrena is a key component of Pfizer’s oncology strategy, helping to offset declining COVID-19 product revenues and drive long-term growth.

FAQs

What is Lorbrena used for?

Lorbrena (lorlatinib) is used for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC), including those who have not received prior treatment and those whose disease has progressed on other ALK inhibitors.

How effective is Lorbrena compared to other ALK inhibitors?

Lorbrena has shown a 72% reduction in the risk of disease progression or death compared to crizotinib, outperforming other second-generation ALK inhibitors like Alecensa and Alunbrig in head-to-head trials.

What are the common side effects of Lorbrena?

Common adverse events include edema, weight gain, peripheral neuropathy, cognitive effects, diarrhea, dyspnea, and hypertriglyceridemia. Treatment discontinuation due to adverse events occurred in 6.7% of patients.

How does Lorbrena perform in treating brain metastases?

Lorbrena has shown exceptional efficacy in treating brain metastases, shrinking tumors in 82% of patients and extending the time to central nervous system progression by 93% over crizotinib.

What are Pfizer’s sales projections for Lorbrena?

Pfizer projects Lorbrena to generate over $1 billion in annual sales by 2030, driven by its strong clinical data and strategic market focus.

Sources

1. Lorbrena Now FDA Approved for First-Line Treatment of Metastatic NSCLC. JHOP Online.
2. Pfizer's Lorbrena Aims High With Ambitious Sales Targets. Finimize.
3. Summary Basis of Decision for Lorbrena. Health Canada.
4. Clinical Trial Results | Lorbrena® (lorlatinib) | Safety Info. Lorbrena.com.
5. Pfizer's Lorbrena breaks into front-line ALK lung cancer, jostling with rivals. FiercePharma.

Last updated: 2025-01-01