science

Lorlatinib

Lorlatinib is a science topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Lorlatinib rather than just read about it. In short: Lorlatinib, sold under the brand name Lorbrena in the United States, Canada, and Japan, and Lorviqua in the European Union, is an anti-cancer medication used for the treatment of non-small cell lung cancer. It is an orally administered inhibitor of anaplastic lymphoma kinase (ALK) and C-ros oncogene 1 (ROS1), two enzymes that play a role in the development of cancer.

Key takeaways

Lorlatinib belongs to science; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Lorlatinib to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Lorlatinib from memory before moving on to harder problems.

Reference excerpt

Lorlatinib, sold under the brand name Lorbrena in the United States, Canada, and Japan, and Lorviqua in the European Union, is an anti-cancer medication used for the treatment of non-small cell lung cancer. It is an orally administered inhibitor of anaplastic lymphoma kinase (ALK) and C-ros oncogene 1 (ROS1), two enzymes that play a role in the development of cancer. It was developed by Pfizer. The most common adverse reactions include edema, peripheral neuropathy, weight gain, cognitive effects, fatigue, dyspnea, arthralgia, diarrhea, mood effects, hypercholesterolemia, hypertriglyceridemia, and cough. Lorlatinib was approved for medical use in the United States in November 2018, and in the European Union in May 2019.

Medical uses Lorlatinib is indicated for the treatment of adults with metastatic non-small cell lung cancer whose tumors are anaplastic lymphoma kinase (ALK)-positive.

Contraindications Lorlatinib must not be combined with strong inducers (i.e. activators) of the liver enzymes CYP3A4/5 if it can be avoided, as serious cases of liver toxicity have been observed under combination with the CYP3A4/5 inducer rifampicin.

Side effects The most common side effects in studies were high blood cholesterol (84% of patients), high blood triglycerides (67%), edema (55%), peripheral neuropathy (48%), cognitive effects (29%), fatigue (28%), weight gain (26%), and mood effects (23%). Serious side effects led to dose reduction in 23% of patients and to termination of lorlatinib treatment in 3% of patients.

Interactions Lorlatinib is metabolized by the enzymes CYP3A4/5. Therefore, CYP3A4/5 inducers such as rifampicin, carbamazepine or St John's wort decrease its concentrations in the blood plasma and can reduce its effectiveness. Additionally, the combination of lorlatinib with rifampicin showed liver toxicity in studies. Inhibitors of these enzymes such as ketoconazole or grapefruit juice increase lorlatinib plasma concentrations, leading to higher toxicity. Lorlatinib is also a (moderate) CYP3A4/5 inducer, so that drugs that are metabolized by these enzymes are broken down more quickly when combined with lorlatinib. Examples include midazolam and ciclosporin. Interactions via other enzymes have only been studied in vitro. According to these findings, lorlatinib may inhibit CYP2C9, UGT1A1 and several transport proteins, induce CYP2B6, and has probably no relevant effect on CYP1A2.

Pharmacology

Mechanism of action

Lorlatinib is a small molecule kinase inhibitor of ALK and ROS1 as well as a number of other kinases. It is active in vitro against many mutated forms of ALK.

Pharmacokinetics

Lorlatinib is taken by mouth and reaches highest blood plasma concentrations 1.2 hours after a single dose, or 2 hours after ingestion when taken regularly. Its absolute bioavailability is 80.8%. Intake with fatty food increases its availability by 5%, which is not considered clinically significant. When in the bloodstream, 66% of the substance are bound to plasma proteins. Lorlatinib is able to cross the blood–brain barrier. Lorlatinib is inactivated by oxidation, mainly through CYP3A4, and by glucuronidation, mainly through UGT1A4. Other CYPs and UGTs play a minor role. Lorlatinib and its metabolites are excreted with a half-life of 23.6 hours after a single dose; 47.7% into the urine (of which less than 1% in unchanged form), and 40.9% into the faeces (9.1% unchanged).

Chemistry Lorlatinib is a white to off-white powder. It has high solubility in 0.1 M hydrochloric acid and very low solubility at a pH over 4.5.

History In November 2018, the US Food and Drug Administration (FDA) granted accelerated approval to lorlatinib for people with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer whose disease has progressed on crizotinib and at least one other anaplastic lymphoma kinase inhibitor for metastatic disease or whose disease has progressed on alectinib or ceritinib as the first anaplastic lymphoma kinase inhibitor therapy for metastatic disease. Approval was based on a subgroup of 215 participants with ALK-positive metastatic NSCLC, previously treated with one or more anaplastic lymphoma kinase inhibitors, enrolled in a non‑randomized, dose-ranging and activity-estimating, multi‑cohort, multi-center study (Study B7461001; NCT01970865). The major efficacy measures were overall response rate (ORR) and intracranial ORR, according to RECIST 1.1, as assessed by an independent central review committee. In March 2021, the FDA granted regular approval to lorlatinib based on data from study B7461006 (NCT03052608), a randomized, multi-center, open-label, active-controlled trial conducted in 296 participants with ALK-positive metastatic non-small cell lung cancer who had not received prior systemic therapy for metastatic disease. Participants were required to have ALK-positive tumors detected by the VENTANA ALK (D5F3) CDx assay. Participants were randomized 1:1 to receive lorlatinib 100 mg orally once daily (n=149) or crizotinib 250 mg orally twice daily (n=147). In the UK, since October 2025, lorlatinib is recommended as a first-line treatment for adults with anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer who have not previously received an anaplastic lymphoma kinase inhibitor.

Society and culture

Legal status In 2015, the US Food and Drug Administration granted lorlatinib orphan drug status for the treatment of anaplastic lymphoma kinase (ALK)-positive or ROS1-positive non-small cell lung cancer. Lorlatinib was approved for medical use in the United States in November 2018, and in the European Union in May 2019.

Research In June 2024, Pfizer announced positive longer-term follow-up results from the phase III CROWN study of lorlatinib in advanced non-small cell lung cancer showing that 60% of participants treated with lorlatinib were alive without disease progression after five years.

References

External links Clinical trial number NCT01970865 for "A Study Of PF-06463922 An ALK/ROS1 Inhibitor In Patients With Advanced Non Small Cell Lung Cancer With Specific Molecular Alterations" at ClinicalTrials.gov

Illustrations

Worked examples

Example 1 — a first encounter with Lorlatinib

Start with the simplest possible case. Write down what Lorlatinib claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In science, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Lorlatinib before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Lorlatinib ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Lorlatinib

In research: Lorlatinib appears in science research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Lorlatinib in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Lorlatinib is common in secondary-school and first-year university syllabi. It links to neighbouring topics Antineoplastic drugs, CYP3A4 inducers, Drugs developed by Pfizer, so understanding it makes those chapters shorter.
In everyday life: Look for Lorlatinib outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Lorlatinib in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Lorlatinib means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Lorlatinib out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Lorlatinib in simple terms?

Why does Lorlatinib matter?

Because it connects several science ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Lorlatinib?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Lorlatinib.