QINLOCK (Ripretinib)

What Is QINLOCK and What Is It Used For?

QINLOCK (ripretinib) is an oral targeted cancer medicine called a switch-control tyrosine kinase inhibitor. It is used to treat adults with advanced gastrointestinal stromal tumor (GIST) whose disease has progressed despite treatment with at least three previous kinase inhibitors, including imatinib. It works by blocking abnormal KIT and PDGFRA proteins that drive cancer cell growth in GIST.

QINLOCK is a modern, molecularly targeted cancer therapy that was specifically developed to address a major unmet need in the treatment of advanced gastrointestinal stromal tumor. Unlike traditional chemotherapy, which damages dividing cells throughout the body, QINLOCK is a precision medicine that selectively targets the abnormal signalling proteins responsible for tumour growth in GIST. This focused mechanism allows it to attack cancer cells while largely sparing normal tissues.

The active substance in QINLOCK is ripretinib, formerly known in clinical development as DCC-2618. It belongs to a group of medicines called tyrosine kinase inhibitors (TKIs), which work by blocking enzymes that relay growth signals inside cancer cells. Ripretinib is distinguished from earlier GIST medicines by its broad activity against multiple mutations in the target kinases, including mutations that typically develop as resistance emerges during earlier lines of treatment.

Gastrointestinal stromal tumor is a rare type of cancer that originates in the connective tissue of the digestive tract, most commonly in the stomach or small intestine. It arises from the interstitial cells of Cajal, sometimes described as the pacemakers of the gut. The vast majority of GISTs are driven by activating mutations in the KIT gene, with a smaller proportion caused by mutations in the related PDGFRA gene. When these proteins are overactive, they continuously signal cells to grow and divide, leading to tumour formation.

QINLOCK was approved by the U.S. Food and Drug Administration (FDA) in 2020 and by the European Medicines Agency (EMA) in 2021 for adults with advanced GIST after progression on at least three previous kinase inhibitors. In many countries, this makes it the standard fourth-line treatment option, offered to patients who have received imatinib, sunitinib, and regorafenib in earlier lines of therapy.

How QINLOCK Works

The mechanism of action of QINLOCK is highly distinctive among cancer medicines. Ripretinib is a so-called switch-control inhibitor, meaning it binds two different regions of the target kinase — the switch pocket and the activation loop — simultaneously. By anchoring both regions, it locks the kinase in an inactive, closed conformation and prevents it from signalling, regardless of many of the mutations that typically allow other TKIs to lose their grip.

In practical terms, this means ripretinib is active against a broad panel of KIT mutations, including common primary mutations in exons 9 and 11, as well as secondary resistance mutations in exons 13, 14, 17, and 18 that frequently emerge during treatment with earlier GIST drugs. It also inhibits PDGFRA mutations, including the historically difficult-to-treat PDGFRA D842V mutation, although the clinical indication is currently limited to GIST after failure of prior kinase inhibitor therapy.

Ripretinib is extensively metabolised in the liver by the cytochrome P450 enzyme CYP3A4, producing an active metabolite called DP-5439, which also contributes to the medicine's overall anti-tumour activity. Both the parent drug and the metabolite circulate in the blood and together maintain inhibition of the target kinases around the clock with once-daily dosing.

The pivotal INVICTUS trial, a randomised, double-blind, placebo-controlled Phase 3 study, demonstrated that ripretinib significantly prolonged progression-free survival compared with placebo in patients with advanced GIST after at least three previous lines of therapy. The median progression-free survival with ripretinib was approximately 6.3 months versus 1.0 month with placebo, alongside a trend toward improved overall survival. These results formed the basis for regulatory approval in the United States, the European Union, and many other regions.

What Should You Know Before Taking QINLOCK?

Before starting QINLOCK, tell your doctor about any history of heart disease, high blood pressure, skin cancers, bleeding problems, liver disease, or planned surgery. QINLOCK must not be used during pregnancy, and reliable contraception is required for both men and women of reproductive potential during and shortly after treatment.

QINLOCK is a powerful targeted medicine that requires careful assessment before treatment begins. Your oncology team will consider your full medical history, current medications, and baseline tests to determine whether QINLOCK is the right option for you, and to put appropriate monitoring in place. Sharing complete and accurate information with your healthcare team is one of the most important steps in ensuring your safety during treatment.

Contraindications

You must not take QINLOCK if:

• You are allergic (hypersensitive) to ripretinib or to any of the other ingredients in the tablets, including lactose, microcrystalline cellulose, or the components of the film coating
• You are pregnant or planning to become pregnant, unless the treating specialist judges the benefit outweighs the known embryo-fetal risk

If you suspect you may be allergic to any ingredient in QINLOCK, discuss this with your doctor or pharmacist before starting treatment.

Warnings and Precautions

Talk to your doctor before taking QINLOCK if any of the following apply to you:

• Skin conditions and previous skin cancers: QINLOCK can cause new primary cutaneous malignancies, including cutaneous squamous cell carcinoma and melanoma. Inform your doctor of any previous skin cancers, moles that have recently changed, or unusual skin lesions
• Hand-foot syndrome (palmar-plantar erythrodysesthesia): Redness, swelling, blistering, or painful skin on the palms of the hands or soles of the feet may develop and can interfere with daily activities
• Hypertension: QINLOCK can raise blood pressure, which should be controlled before starting therapy and monitored regularly throughout treatment
• Heart problems: Ripretinib can reduce the heart's pumping function (left ventricular ejection fraction). A history of heart failure, coronary artery disease, arrhythmias, or significant structural heart disease warrants additional assessment, typically with an echocardiogram or multigated acquisition (MUGA) scan
• Planned surgery: QINLOCK may impair wound healing. Treatment usually needs to be paused at least one week before planned surgery and only resumed once wound healing is judged adequate by the surgical team
• Liver problems: Ripretinib is extensively metabolised in the liver; severe liver impairment requires caution, and dose adjustment may be considered based on individual pharmacokinetics
• Sun exposure: Skin should be protected from direct sunlight with clothing, hats, and a broad-spectrum sunscreen. Patients should receive regular dermatological examinations during treatment
• Older age: Elderly patients may be more susceptible to side effects and require closer monitoring of blood pressure, cardiac function, and laboratory values

Tests and Monitoring

Before starting QINLOCK, and regularly during treatment, your doctor will perform a series of assessments designed to detect problems early. Typical monitoring includes:

• Full dermatological examination at baseline and at regular intervals (for example, every eight weeks) to screen for new skin lesions and skin cancers
• Blood pressure measurement at every clinical visit, with more frequent home monitoring if hypertension develops
• Echocardiogram or MUGA scan at baseline and periodically to assess left ventricular ejection fraction, particularly in patients with known cardiac risk factors
• Blood tests including full blood count, liver function tests, electrolytes, phosphate, magnesium, triglycerides, and cholesterol
• Pregnancy test in women of reproductive potential before starting treatment
• Imaging (commonly CT or MRI) every 8–12 weeks to assess disease response

Pregnancy and Breastfeeding

QINLOCK can harm an unborn baby based on its mechanism of action and findings from animal reproduction studies. If you are pregnant, think you may be pregnant, or are planning to become pregnant, tell your doctor before starting treatment.

• Women of reproductive potential must use effective contraception during treatment and for at least one week after the final dose of QINLOCK
• Men with female partners of reproductive potential should use effective contraception during treatment and for at least one week after the final dose
• A pregnancy test is typically performed before starting treatment and whenever clinically indicated
• If you become pregnant while taking QINLOCK, contact your doctor immediately
• Breastfeeding is not recommended during treatment with QINLOCK and for at least one week after the final dose, because ripretinib and its metabolite may pass into breast milk and harm a nursing infant

Driving and Operating Machinery

QINLOCK is not generally expected to affect the ability to drive or use machines. However, some patients may experience fatigue, dizziness, headache, or blurred vision. If you feel unwell or notice symptoms that could impair your ability to concentrate or react, you should not drive or operate machinery until the symptoms resolve and you have discussed them with your doctor.

Children and Adolescents

QINLOCK is not approved for use in children and adolescents under 18 years of age. The safety and effectiveness of ripretinib have not been established in this age group, and paediatric patients with KIT- or PDGFRA-driven disorders are managed according to specialist protocols by paediatric oncologists.

How Does QINLOCK Interact with Other Drugs?

QINLOCK is primarily metabolised by the CYP3A enzyme system, so medicines and foods that strongly affect CYP3A can change its blood levels. Strong CYP3A inducers (such as rifampin or St. John's wort) should generally be avoided, and strong CYP3A inhibitors (such as ketoconazole or clarithromycin) should be used with caution and close monitoring.

Many medicines, including common antibiotics, antifungals, anticonvulsants, and herbal products, can interact with QINLOCK through the liver enzyme CYP3A. These interactions can either reduce ripretinib exposure — potentially making the treatment less effective — or increase it, raising the risk of side effects. Before starting QINLOCK, provide your doctor and pharmacist with a complete list of every medicine you take, including over-the-counter products, vitamins, and herbal supplements. Do not start any new medicine without checking with your oncology team first.

Major Interactions

Minor Interactions and Practical Considerations

Beyond the major interactions described above, several other medications warrant monitoring or dose adjustment when co-administered with QINLOCK. Acid-reducing agents such as proton pump inhibitors and H2 antagonists are not expected to significantly alter ripretinib absorption based on available pharmacokinetic data, so routine dose separation is usually not required. However, clinicians may still assess the overall medication burden to avoid unnecessary prescribing.

Live vaccines, such as measles-mumps-rubella (MMR), varicella, yellow fever, and oral polio vaccines, should generally be avoided in patients receiving QINLOCK. Although ripretinib is not broadly immunosuppressive in the way that cytotoxic chemotherapy can be, combining targeted cancer therapy with live vaccines is typically discouraged until the treating team has reviewed the specific situation. Inactivated vaccines, including seasonal influenza and COVID-19 vaccines, are generally considered safe and are encouraged according to local guidance.

What Is the Correct Dosage of QINLOCK?

The standard dose of QINLOCK is 150 mg taken orally once daily, given as three 50 mg tablets at around the same time each day, with or without food. Treatment continues until the disease worsens or side effects become unacceptable. Your doctor may interrupt, reduce, or discontinue the dose based on how you respond and what side effects you experience.

QINLOCK is prescribed and managed by oncologists experienced in treating gastrointestinal stromal tumor. Unlike chemotherapy regimens with fixed cycles, QINLOCK is taken continuously on an outpatient basis for as long as it remains effective and tolerated. Adherence to the prescribed schedule is important, as missed doses and significant dose reductions can affect how well the medicine controls your disease.

Adults

Children

QINLOCK is not approved for use in children and adolescents under 18 years of age. The safety and effectiveness of ripretinib in paediatric patients have not been established, and no paediatric dose has been recommended by regulatory authorities.

Elderly

No specific dose adjustment is required for patients based on age alone. Clinical trials included patients older than 65 years and, in some cases, older than 75 years, without identifying clinically meaningful differences in overall efficacy compared with younger adults. However, elderly patients are more likely to have comorbid cardiovascular disease, reduced organ function, and polypharmacy, which warrant closer monitoring of blood pressure, cardiac function, and laboratory values.

Kidney and Liver Impairment

In patients with mild or moderate kidney impairment, no dose adjustment is required based on available data. Limited information is available on patients with severe kidney impairment, and caution is advised in this group. In patients with mild hepatic impairment, the recommended dose remains 150 mg once daily; there is limited experience with moderate and severe hepatic impairment, and more frequent monitoring is appropriate. Your doctor may consult local prescribing information for the most current guidance.

Dose Modifications for Side Effects

If side effects occur, your doctor may adjust the dose using a stepwise approach. Common modifications include:

• First reduction: From 150 mg once daily to 100 mg once daily
• Further reduction: From 100 mg once daily to 50 mg once daily
• Discontinuation: If 50 mg once daily is not tolerated, QINLOCK is permanently stopped

Temporary dose interruptions are often used to manage acute side effects, with treatment resumed at the same or a reduced dose once the reaction has improved. Do not adjust your dose on your own — always follow your doctor's instructions.

Missed Dose

If you miss a dose of QINLOCK and it has been less than eight hours since your usual dosing time, take the missed dose as soon as you remember. If more than eight hours have passed, skip the missed dose and take the next dose at your regular time. Do not take a double dose to make up for a missed dose. Keep a simple log or use a pillbox to help you remember.

Vomiting After a Dose

If you vomit after taking QINLOCK, do not take an additional dose. Resume your regular schedule with the next scheduled dose. If vomiting is frequent or severe, contact your oncology team for advice on managing the problem and assessing whether drug absorption is adequate.

Overdose

If you take more QINLOCK than prescribed, contact your doctor, pharmacist, or local poison control centre immediately. Take the medicine package with you so that healthcare professionals can identify the product and strength. There is no specific antidote for ripretinib overdose; treatment is supportive and focused on managing symptoms.

What Are the Side Effects of QINLOCK?

Like all medicines, QINLOCK can cause side effects, although not everyone experiences them. The most frequent side effects include hair loss, fatigue, nausea, abdominal pain, constipation, muscle pain, diarrhea, decreased appetite, hand-foot syndrome, and vomiting. Serious but less common side effects include new skin cancers, high blood pressure, and decreased heart function.

The side effect profile of QINLOCK is generally consistent with that of other targeted kinase inhibitors, but it has some distinctive features. Skin-related reactions, including hair loss and hand-foot syndrome, are particularly common. While most side effects are mild to moderate, a small proportion can become severe or life-threatening if not recognised and managed promptly. Regular review with your oncology team is essential so that side effects can be addressed early.

Side Effects by Frequency

The following side effects have been reported in clinical trials and post-marketing experience with QINLOCK. Frequencies are approximate and may vary between studies and patient populations.

Skin-Related Side Effects Explained

Skin and hair changes are the most visible side effects of QINLOCK. Hair loss is very common and usually develops within the first few months of treatment; it is typically reversible after discontinuation. Hand-foot syndrome typically presents as redness, tingling, swelling, or pain on the palms and soles and can progress to peeling and blistering in severe cases. Simple measures such as avoiding hot water, wearing loose shoes, using emollients, and avoiding friction on the hands and feet can significantly reduce symptoms. Moisturising creams and urea-based preparations are often recommended.

QINLOCK can also cause the development of new skin cancers, most commonly cutaneous squamous cell carcinoma, keratoacanthomas, and melanoma. These are usually localised and can be removed surgically, but early detection is crucial. Regular dermatological examinations at baseline and every one to two months during treatment allow new lesions to be identified and managed promptly.

Cardiovascular Side Effects

Raised blood pressure is a common side effect of many targeted cancer therapies, including QINLOCK. It can develop within the first weeks of treatment and is typically managed with standard antihypertensive medicines such as ACE inhibitors, angiotensin receptor blockers, or calcium channel blockers. Home blood pressure monitoring is often recommended, with thresholds for contacting the oncology team defined by the treating specialist.

Decreased cardiac function, measured as a drop in left ventricular ejection fraction, is less common but clinically important. Patients with pre-existing heart disease, prior anthracycline chemotherapy, or other cardiotoxic exposures may be at higher risk. Baseline and periodic echocardiograms or MUGA scans are used to detect changes early, when dose adjustment and cardiology involvement can often reverse or stabilise the decline.

Managing and Reporting Side Effects

Most side effects can be managed effectively if they are recognised early. Your oncology team will outline practical steps such as dietary advice for nausea, laxatives for constipation, topical creams for skin changes, and antihypertensive medicines for blood pressure. Do not hesitate to report any new or worsening symptom, even if it seems minor. Grading and documenting side effects help guide decisions about dose interruption, dose reduction, or supportive care.

You can also report suspected side effects to your national regulatory authority's pharmacovigilance system. Post-marketing reporting helps build a broader understanding of how QINLOCK performs outside the controlled environment of clinical trials and can identify rare or late-emerging adverse reactions.

How Should You Store QINLOCK?

Store QINLOCK in the original bottle at room temperature, below 30°C. Keep the bottle tightly closed to protect the tablets from moisture and keep the desiccant packet inside until all tablets have been used. Store out of the sight and reach of children, and do not use after the expiry date on the label.

Proper storage keeps QINLOCK effective throughout its shelf life and protects your household from accidental exposure. Because ripretinib is a high-potency anticancer medicine, handling and storage also involve a few precautions that are not always necessary for everyday medicines.

Keep QINLOCK in its original bottle with the cap tightly closed. The bottle contains a desiccant to protect tablets from humidity; do not remove the desiccant and do not transfer tablets to a pillbox or other container unless advised by your pharmacist. Store below 30°C and avoid exposure to direct sunlight, heat, or moisture. The bathroom is generally not an ideal storage location because of temperature swings and humidity; a dry cupboard away from food is usually preferable.

Do not use QINLOCK after the expiry date shown on the bottle and outer packaging. The expiry date refers to the last day of the stated month. Do not use the medicine if you notice any damage to the packaging, discoloration of the tablets, or other unusual changes.

Handling Precautions

Use dry hands to remove tablets from the bottle, and avoid crushing, breaking, or splitting them. If a tablet is accidentally crushed or broken, avoid inhaling dust and wash your hands thoroughly with soap and water. If powder from a crushed tablet comes into contact with skin, rinse the area with water. Caregivers who help a patient take the medicine may consider wearing disposable gloves when handling broken tablets.

What Does QINLOCK Contain?

Each QINLOCK tablet contains 50 mg of ripretinib as the active ingredient, together with inactive ingredients that make up the tablet core and the film coating. The inactive ingredients include lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, povidone, magnesium stearate, and a film-coating mixture.

Understanding the composition of QINLOCK is important if you have allergies, food intolerances, or dietary restrictions. Each 50 mg film-coated tablet contains both the therapeutically active ingredient and several excipients (inactive ingredients) that ensure the medicine is stable, safe, and effectively absorbed from the digestive tract.

Active Ingredient

• Ripretinib — 50 mg per film-coated tablet

Excipients (Inactive Ingredients)

QINLOCK tablets typically contain the following inactive ingredients:

• Lactose monohydrate — provides tablet bulk and influences drug release
• Microcrystalline cellulose — acts as a binder and filler
• Sodium starch glycolate — a disintegrant that helps the tablet break up in the stomach
• Povidone — a binder that holds the tablet structure together
• Magnesium stearate — a lubricant used during tablet manufacture
• Film coating — typically containing polyvinyl alcohol, titanium dioxide, macrogol (polyethylene glycol), talc, and pigments such as iron oxide

Important Composition Notes

Patients with certain hereditary conditions or allergies should take note of the following:

• Lactose: The tablets contain lactose. Patients with galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should discuss this with their doctor before starting QINLOCK
• Sodium: QINLOCK contains a very small amount of sodium (typically less than 1 mmol per tablet), so it is considered essentially "sodium-free" for dietary purposes
• Gluten: QINLOCK is generally considered suitable for patients with coeliac disease, as it does not contain wheat-derived excipients, but patients with severe gluten sensitivity should confirm with their pharmacist using the latest product information
• Allergens: If you have known sensitivity to any excipient, tell your doctor or pharmacist before starting treatment

Appearance and Packaging

QINLOCK 50 mg film-coated tablets are typically presented as white, oval-shaped tablets debossed with identifying markings. They are supplied in a high-density polyethylene (HDPE) bottle with a child-resistant closure and a desiccant canister to protect against moisture. Each bottle typically contains 30 or 90 tablets; country-specific pack sizes may vary. Always check the information leaflet included in your pack for the most accurate description of the product dispensed in your region.