Expert Exchange Video Series

Leading cancer experts discuss the latest research about Qinlock and the management of advanced GIST in adult patients treated with ≥3 prior kinase inhibitors, including imatinib, in clinical practice.

Patient Case Review: QINLOCK for 4th‑Line Advanced GIST with Mark Agulnik, MD, PhD

Mark Agulnik, MD, PhD, from the City of Hope Comprehensive Cancer Center in Duarte, California, discusses a hypothetical case based on an actual patient treated with QINLOCK for 4th‑line advanced GIST. He also reviews efficacy and safety data supporting the use of QINLOCK for 4th‑line advanced GIST.

Hello. My name is Dr Mark Agulnik, and I’m a Clinical Professor in the Department of Medical Oncology and Therapeutics Research at the City of Hope Comprehensive Cancer Center in Duarte, California. I’m excited to have the opportunity to talk to you about Qinlock, or ripretinib, a treatment option for adult patients with advanced gastrointestinal stromal tumors, or GISTs, who have been treated with 3 or more prior tyrosine kinase inhibitors, or TKIs, including imatinib.

I have been involved in GIST clinical trials and have managed patients on Qinlock. In this video, I will also be discussing Susan, who is based on a real-life patient case of mine who has been prescribed Qinlock.

Let’s begin with a case of a patient I have been treating for a number of years. I first met Susan when she was 60 years old. At that time, in early 2015, she initially presented with right upper quadrant pain, ultimately diagnosed with a 5.2-cm GIST. A surgical resection was performed and mutational testing of her tumor revealed an exon 11 mutation.

When we first met, she was overwhelmed with her diagnosis because she had most recently lost her husband to lung cancer. We recommended 3 years of adjuvant therapy with imatinib, but due to her circumstances and new diagnosis, she decided to defer adjuvant treatment at that time.

She was compliant with her follow-up care and had routine monitoring and scans per standard guidelines.

In March 2017, two years after her initial diagnosis, Susan, although asymptomatic at the time, was found to have a new left upper quadrant mass, biopsied and confirmed to be recurrent GIST. Several liver metastases were discovered as well.

Since her initial diagnosis, Susan’s son and daughter-in-law had moved back into the area with their one-and-a-half year-old twins. She became the primary caretaker of her grandchildren, and therefore, she was now willing to start imatinib, wanting to do whatever it took to fight her disease.

Susan began imatinib 400 mg per day in March 2017. She did very well on this dose for 2 years, with slight periorbital edema and occasional diarrhea as her only side effects. In March 2019, disease progression was documented on positron emission tomography, or PET, scan, at which point the imatinib dose was increased to 800 mg per day. However, after a few months of stable disease on the higher imatinib dose, her disease began to progress and become widespread. It was clear that we needed to move on to other treatment options.

I started Susan on sunitinib in July 2019 at a starting dose of 50 mg daily with the standard 4 weeks on, 2 weeks off protocol. Her disease was well-controlled; however, she did experience mild hand-foot syndrome, which resolved over time with supportive care. Approximately 6 months later, in January of 2020, Susan once again developed documented disease progression. We discussed the option of regorafenib, the 3rd-line approved therapy for GIST.

Susan started regorafenib therapy and her disease stabilized. She did complain of a hoarse voice, or dysphonia, a somewhat unique and known side effect of regorafenib therapy. Unfortunately, approximately 5 months later, Susan’s disease had progressed despite regorafenib therapy.

Considering her disease progression as well as Susan’s desire to fight her disease, we discussed the question on what to do next to help treat Susan.

Before we get into Susan’s next treatment, let’s talk about the role of mutations in patients with advanced GIST. This is a highly complex disease with a myriad of mutations fueling resistance and progression. As seen in this table, GIST is often driven by primary, activating mutations in kinase genes KIT and PDGFRA.

70% to 80% of GISTs have mutations in one or more regions, or exons, of the KIT gene, as is the case in our patient, Susan. 5% to 10% of tumors have mutations in the PDGFRA gene, and 10% to 15% of tumors are wild type mutations.

The wide range of mutations that exist in GIST highlight the need for therapies that target these key mutations.

Complicating treatment even further, following failure of frontline TKI therapy, patients with GIST often have multiple tumors, each of which can be driven by different secondary mutations. There is broad inter- and intra-tumor heterogeneity that exists among secondary resistance mutations—in other words, a single patient with GIST may have multiple mutations within or between tumors.

These factors can contribute to patients with resistant GIST progressing quickly through second- and third-line therapies. Until recently, we have had no approved therapies for patients like Susan.

Luckily, Qinlock had been approved in May 2020 as a fourth-line treatment option for patients with advanced GIST who had received 3 or more prior kinase inhibitors, including imatinib. Until Qinlock, we have historically not had an approved treatment option for a patient like Susan at this stage of her disease, so we were excited to offer her Qinlock for her advanced unresectable GIST.

Let’s now discuss how Qinlock works. Qinlock is the first and only switch control kinase inhibitor engineered to block the drivers of resistance in advanced GIST, and is the first approved treatment option for adult patients with advanced GIST who have received prior treatment with 3 or more kinase inhibitors, including imatinib.

Kinase activation requires the interaction of two critical regions: the activation switch and the switch pocket. Mutations in tyrosine kinases, such as KIT or PDGFRA, cause uncontrolled interaction of the activation switch with the switch pocket. This activates the kinase and leads to upregulation of kinase signaling, which drives cancer cell proliferation and/or survival.

Qinlock provides broad-spectrum inhibition of KIT and PDGFRA kinase signaling in vitro through a dual mechanism of action. In fact, Qinlock was specifically engineered to block the drivers of resistance in advanced GIST.

Based on preclinical evidence, Qinlock binds to both the activation switch and switch pocket and locks the kinase in the inactive state. This dual mechanism of action has been shown to potently inhibit kinase activation across the broad spectrum of mutations in KIT and PDGFRA kinases known to drive drug resistance and disease progression in advanced GIST.

Qinlock was approved by the FDA based on the results of the Phase 3 randomized Invictus trial. Patients were randomized in a 2-to-1 ratio to Qinlock 150 mg once daily, or to placebo. Upon disease progression, patients in the placebo arm had two options. They could either cross over to open-label Qinlock 150 mg once daily or they could discontinue the study treatment.

The primary endpoint was progression‑free survival, or PFS. Secondary endpoints included objective response rate, or ORR; overall survival, or OS; quality of life; and safety.

The primary data analysis was conducted from a May 31, 2019 data cut-off date. A follow-up analysis was conducted with 9 months of additional follow-up, from a March 9, 2020 data cut-off date. Data included in follow-up analyses will continue to mature as patient follow-up is conducted and the following efficacy result estimates are therefore subject to inherent limitations.

This trial enrolled the most heavily pretreated patient population in a Phase 3, 4th-line or greater, GIST setting. 64% in the ripretinib arm and 61% in the placebo arm had received 3 prior therapies, and 36% in the ripretinib arm and 39% in the placebo arm had received 4 or more therapies. Invictus included patients with Eastern Cooperative Oncology Group performance statuses of 0 to 2, and enrolled patients regardless of mutation status. Patient characteristics reflect a real world, 4th-line GIST population and were generally balanced between Qinlock and placebo. Based on the patient characteristics, Susan would have been eligible for inclusion in Invictus, and is therefore representative of the participants in this clinical trial.

Let’s now take a look at the efficacy results. Efficacy results showed that QINLOCK demonstrated a powerful PFS results in INVICTUS, with a superior median PFS versus placebo in the primary analysis. In the follow-up analysis, as you see here in this figure, these results were consistent, with a median PFS of 6.3 months with QINLOCK versus 1 month for placebo, with a hazard ratio of 0.16 translating into an 84% reduction in the risk of progression or death.

Furthermore, I find it reassuring that Qinlock was granted preferred and Category 1 designation by the NCCN as the only therapy recommended for 4th‑line advanced GIST.

For Qinlock-treated patients, estimated PFS at 6, 12, and 18 months was 51%, 23.6%, and 12.6%, respectively. To note, data will continue to mature as additional patient follow‑up is conducted and these estimates are therefore subject to inherent limitations. In my experience, some patients may stay progression free for an extended period of time.

I should note that an updated subgroup analysis of the PFS data from Invictus was presented at the annual meeting of the Connective Tissue Oncology Society, or CTOS, in 2020. As shown in this figure, consistent PFS results were seen for Qinlock across baseline primary mutation types.

The data presented give me further confidence that patients like Susan are expected to experience meaningful PFS from Qinlock regardless of mutational status. Importantly, these data also emphasize the fact that mutational testing is not required when administering Qinlock as per the FDA indication.

In Invictus, clinically meaningful improvement in ORR was observed. The confirmed objective response rate by blinded independent central review was 9.4% with Qinlock vs 0% with placebo in the primary analysis, with a P‑value of 0.0504.

In the follow-up analysis, ORR was 11.8% for Qinlock vs 0% for placebo.

In addition, clinically meaningful OS was observed with Qinlock.

In the primary analysis, with a median OS of 15.1 months for Qinlock vs 6.6 months for placebo.

In a follow-up analysis, the median OS was not reached for Qinlock versus 6.3 months for placebo, with a hazard ratio of 0.42 translating into a 58% reduction in risk of death, which is certainly very encouraging for this heavily pre-treated patient population with advanced disease.

To note, OS was a secondary endpoint in the Invictus trial, and was not evaluated for statistical significance as a result of the sequential testing procedure used for the secondary endpoints of ORR and OS. Additionally, data in the follow-up analysis will continue to mature as additional patient follow-up is conducted and estimates are therefore subject to inherent limitations.

Additional estimated OS landmarks can be seen here in this table. With 9 months of additional follow-up after the primary analysis of Invictus, the estimated landmark OS for patients randomized to Qinlock at 6, 12, 18, and 24 months was 84.3%, 65.1%, 53%, and 50.6%, respectively. As mentioned previously, it is important to note that data will continue to mature as additional patient follow-up is conducted and these estimates are therefore subject to inherent limitations.

Based on the data from Invictus, Qinlock was associated with powerful PFS results and clinically meaningful OS outcomes, which I find to be to be reassuring when selecting a therapy for my patients like Susan, who have progressed beyond third-line therapy for GIST or who may not be tolerating their current treatment well.

Next, let’s move on to discuss safety and tolerability for patients like Susan in more detail.

The safety of Qinlock was established across the broad range of patients enrolled in the Invictus trial.

Generally, from my experience, Qinlock is well tolerated and, although adverse events can occur, they are generally manageable.

Some serious adverse events in Qinlock-treated patients include abdominal pain, anemia, nausea, and vomiting.

As we saw from the primary analysis of the trial, rates of dose modification were similar between Qinlock and placebo. Specifically, dose reductions for Qinlock were 7% versus 2% with placebo, and there was a smaller percentage of discontinuation due to adverse reactions with Qinlock versus placebo.

Safety findings after 9 months of additional follow-up were consistent with the primary analysis.

In addition, quality of life was also assessed as a pre-specified secondary endpoint in Invictus, which showed that patients on Qinlock had maintained their self-reported health, physical function, and role function, versus a decline with placebo.

Based on the powerful efficacy results, safety profile, and quality of life data for Qinlock, I had great confidence in prescribing this therapy to Susan.

The most common adverse events that you can expect to see with Qinlock include alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar‑plantar erythrodysesthesia syndrome, or PPES, and vomiting. The most common Grade 3 or 4 laboratory abnormalities were increased lipase and decreased phosphate.

Although rare, there are some serious additional and potential risks that you need to watch out for and inform your patients of. These include PPES, new primary cutaneous malignancies, hypertension, cardiac dysfunction, risk of impaired wound healing, and embryo‑fetal toxicity.

If you are initiating Qinlock in a patient like Susan, you should feel confident in the safety profile, as most patients did and stayed well on therapy. In fact, in the primary analysis, over 90% of patients did not discontinue or need to dose reduce on therapy, and, as we discussed earlier, quality of life was maintained in study participants receiving Qinlock. This is exceptionally important as I often get questions from my patients on how they might feel, especially for those who had experienced severe side effects on second- and third-line therapy.

Now, let’s take a look at how Susan has been doing on Qinlock.

At her 6-month follow-up with me, Susan was found to be responding to and tolerating Qinlock well. We are seeing a modest amount of tumor shrinkage, and she reported a maintenance of quality of life. Additionally, Susan is progression free and the exploratory analysis of Qinlock demonstrating broad mutational coverage gives me confidence. She did experience some thinning of her hair; however, with help of a stylist, she was able to find a cut and hairstyle that optimized her look and hair coverage. Given Susan’s response to therapy, we will continue treatment with Qinlock until Susan experiences disease progression or unacceptable toxicity.

In summary, we are truly excited to have a treatment for 4th-line advanced GIST that works differently for patients like Susan, who are in significant need for additional options like Qinlock – the first and only switch control kinase inhibitor for advanced GIST.

Qinlock demonstrated powerful PFS in the Invictus study and most patients did well on therapy. In fact, efficacy was consistent regardless of the type of driver mutation present – subjects’ baseline mutations included KIT positive, PDGFRA positive, or wild type.

Side effects are generally manageable, and most patients were able to start and stay on the full indicated dose of 150 mg daily, with or without food. Mutational testing is not required prior to administration of Qinlock, and patients can be treated regardless of mutational status, sequence of prior therapies, evidence of progression, or performance status.

As in Susan’s case, if a patient is developing progression on their third-line GIST treatment or is perhaps no longer able to tolerate third-line treatment, you can consider Qinlock as an appropriate treatment option for them. In fact, Qinlock was granted both preferred and Category 1 designation from the NCCN as the only recommended 4th‑line therapy for advanced GIST.

My patient, Susan, was thrilled to have Qinlock as a treatment option, and so far, she has been doing very well on therapy.

Thank you so much for joining me in this presentation about Susan, our patient with advanced GIST. Qinlock is an exciting treatment option for patients like Susan in the fourth-line setting and beyond.

 

Indication

QINLOCK is a kinase inhibitor indicated for the treatment of adult patients with advanced gastrointestinal stromal tumor (GIST) who have received prior treatment with 3 or more kinase inhibitors, including imatinib.1

Select Safety Information

  • Serious adverse reactions occurring in >2% of patients were abdominal pain (4.7%), anemia (3.5%), nausea (2.4%), and vomiting (2.4%)1
  • The most common adverse reactions (≥20%) were alopecia (52%), fatigue (42%), nausea (39%), abdominal pain (36%), constipation (34%), myalgia (32%), diarrhea (28%), decreased appetite (27%), PPES (21%), and vomiting (21%). The most common Grade 3 or 4 laboratory abnormalities (≥4%) were increase lipase (7%) and decreased phosphate (5%)1

See below for complete Important Safety Information.

Clinical Experience with Qinlock for 4th-Line Advanced gist with Kathleen Polson, NP

Kathleen Polson, NP, from the Dana Farber Cancer Institute in Boston, MA, shares her clinical experience caring for patients with 4th-line advanced gist treated with Qinlock, and highlights the latest efficacy and safety data.

Hello. My name is Kathleen Polson and I am a Nurse Practitioner at the Dana-Farber Cancer Institute in Boston, Massachusetts. Today, I will be talking about Qinlock, or ripretinib, a treatment option for patients with advanced gastrointestinal stromal tumors, or GISTs, who have been treated with 3 or more prior tyrosine kinase inhibitors, including imatinib. I have been involved in the early development of Qinlock and have managed patients on Qinlock's clinical trials, including the Invictus trial that we will be talking about today.

Qinlock was approved by the FDA for 4th‑line GIST, where previously we have not had any 4th‑line treatment options for this area of high unmet need for patients. Qinlock is a switch‑control kinase inhibitor that has a unique mechanism of action and was specifically designed to block the drivers of resistance in advanced GIST. Next, let’s move on to reviewing the Invictus trial.

Qinlock was approved by the FDA based on the results of the Phase 3, randomized Invictus trial. This trial enrolled the most heavily pre‑treated patient population in a Phase 3, 4th-line or greater, GIST setting. Patients were randomized in a 2‑to‑1 ratio to Qinlock 150 mg once daily, or to placebo. Upon disease progression, patients in the placebo arm had two options. They could either cross over to openlabel Qinlock 150 mg once daily, or they could discontinue the study treatment.

The primary data analysis was conducted from the May 31, 2019 data cut-off date. A follow-up analysis was conducted with 9 months of additional follow-up, with a March 9, 2020 data cut-off date.

Qinlock demonstrated a powerful progressionfree survival, or PFS, benefit in Invictus, with a superior median PFS of 6.3 months vs 1 month in the primary analysis, which was an 85% reduction in the risk of progression or death.

In the exploratory follow-up analysis after 9 months of additional follow-up, PFS results remained consistent. Median PFS for Qinlock was 6.3 months vs 1 month for placebo, with a hazard ratio of 0.16.

Furthermore, I find it reassuring that Qinlock was granted preferred and Category 1 designation by the NCCN as the only therapy recommended for 4th-line advanced GIST.

In addition, clinically meaningful overall survival, or OS, was observed with Qinlock in the primary analysis, with a median OS of 15.1 months for Qinlock vs 6.6 months for placebo.

In the exploratory follow-up analysis after 9 months of additional follow-up, median OS was not reached for Qinlock vs 6.3 months for placebo. This resulted in a 58% reduction in the risk of death or a hazard ratio of 0.42.

Furthermore, in the primary analysis, the objective response rate, or ORR, was 9.4% with Qinlock vs 0% with placebo, with a P‑value of 0.0504.

In the exploratory follow-up analysis after 9 months of additional follow-up, the ORR was 11.8% for Qinlock vs 0% for placebo.

The safety of Qinlock was established across the broad range of patients enrolled in the Invictus trial.

Generally, from my experience, Qinlock is very well tolerated and, although adverse events can occur, they are manageable.

The most common serious adverse events in Qinlock‑treated patients include abdominal pain, anemia, nausea, and vomiting.

As we saw in the trial, rates of dose modification were similar between Qinlock and placebo. Specifically, dose reductions for Qinlock were 7% versus 2% with placebo, and there was a smaller percentage of discontinuation due to adverse reactions with Qinlock versus placebo.

The most common adverse events that you can expect to see with Qinlock include alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar‑plantar erythrodysesthesia syndrome, or PPES, and vomiting. The most common Grade 3 or 4 laboratory abnormalities were increased lipase and decreased phosphate.

I find it to be very important to set expectations upfront with my patients regarding the more common adverse events and proactively manage symptomatic side effects, if possible. Furthermore, I have my patients keep a diary to track any symptoms that may occur so that we can evaluate at our regular visits. Later in this presentation, we will dive further into alopecia and PPES management.

In addition, quality of life was also assessed as a prespecified secondary endpoint in Invictus, which showed that patients on Qinlock had maintained their self‑reported health, physical function, and role function, versus a decline with placebo. I find these data to be encouraging, because in my experience, my patients on Qinlock were able to maintain key aspects of their quality of life, as well.

If you are initiating Qinlock in a new patient or had a patient ask about Qinlock, you should feel confident managing as most patients will do and stay well on therapy. We saw this as over 90% of patients did not discontinue or need to dose reduce on therapy, and as we discussed earlier, quality of life was maintained with participants in the study. This is important as I often get questions from my patients on how they might feel, especially for those who had experienced severe side effects on 2nd-line and 3rd-line therapy.

Dosing is straightforward with Qinlock – it is dosed 150 mg once daily with or without food and mutational testing is not required prior to administration or to be eligible for Qinlock.

Although rare, there are some serious additional and potential risks that you need to watch out for and inform your patients of. These include PPES, new primary cutaneous malignancies, hypertension, cardiac dysfunction, risk of impaired wound healing, and embryo‑fetal toxicity.

There was no Grade 3 PPES seen with Qinlock in Invictus, and I have also found that PPES is generally mild for patients we have managed. Typically, we encourage proactive management with hand creams, soothing ointments, and supportive hand- and foot-wear.

While alopecia can occur, the majority of alopecia was mild or Grade 1; however, it can be as severe as Grade 2. I always counsel my patients that they may see potential changes to their hair volume, color, texture, thinning, or loss. If this occurs, there are many things that we can do to enhance the appearance of a patient’s hair, including alternate hairstyles, coloring, hair powders, or headpieces.

It is recommended to manage the potential side effect of muscle and joint pain with aggressive symptom management up front. It is important to note that, in my personal experience managing patients, this toxicity has decreased and even resolved in many patients after the first couple of cycles.

I have found that patients tend to tolerate Qinlock very well. Of note, some of the adverse events may be different than those of similar agents in this class.

Qinlock is a treatment for advanced GIST that works differently for our patients who are in significant need for additional options, and it is also the first and only switch‑control kinase inhibitor for advanced GIST.

Qinlock demonstrated powerful PFS in the Invictus study, and most patients did well on therapy.

Side effects are manageable, and most patients were able to start and stay on the full indicated dose of 150 mg daily, with or without food.

Mutational testing is not required prior to administration of Qinlock, and patients can be treated regardless of mutational status, sequence of prior therapies, evidence of progression, or performance status.

If a patient is no longer able to tolerate or is developing progression on their 3rd-line GIST treatment, you can consider Qinlock as an appropriate treatment option for them.

Thank you so much for joining me in this presentation about Qinlock – a proven treatment option for our adult patients with advanced GIST in the 4th-line setting and beyond.

 

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Reference: 1. QINLOCK [package insert]. Waltham, MA: Deciphera Pharmaceuticals, Inc; 2021.


Important Safety Information

There are no contraindications for Qinlock.

Palmar‑plantar erythrodysesthesia syndrome (PPES): In INVICTUS, Grade 1–2 PPES occurred in 21% of the 85 patients who received Qinlock. PPES led to dose discontinuation in 1.2% of patients, dose interruption in 2.4% of patients, and dose reduction in 1.2% of patients. Based on severity, withhold Qinlock and then resume at same or reduced dose.

New Primary Cutaneous Malignancies: In INVICTUS, cutaneous squamous cell carcinoma (cuSCC) occurred in 4.7% of the 85 patients who received Qinlock with a median time to event of 4.6 months (range 3.8 to 6 months). In the pooled safety population, cuSCC and keratoacanthoma occurred in 7% and 1.9% of 351 patients, respectively. In INVICTUS, melanoma occurred in 2.4% of the 85 patients who received Qinlock. In the pooled safety population, melanoma occurred in 0.9% of 351 patients. Perform dermatologic evaluations when initiating Qinlock and routinely during treatment. Manage suspicious skin lesions with excision and dermatopathologic evaluation. Continue Qinlock at the same dose.

Hypertension: In INVICTUS, Grade 1–3 hypertension occurred in 14% of the 85 patients who received Qinlock, including Grade 3 hypertension in 7% of patients. Do not initiate Qinlock in patients with uncontrolled hypertension. Monitor blood pressure as clinically indicated. Based on severity, withhold Qinlock and then resume at same or reduced dose or permanently discontinue.

Cardiac Dysfunction: In INVICTUS, cardiac failure occurred in 1.2% of the 85 patients who received Qinlock. In the pooled safety population, cardiac dysfunction (including cardiac failure, acute left ventricular failure, diastolic dysfunction, and ventricular hypertrophy) occurred in 1.7% of 351 patients, including Grade 3 adverse reactions in 1.1% of patients.

In INVICTUS, Grade 3 decreased ejection fraction occurred in 2.6% of the 77 patients who received Qinlock and who had a baseline and at least one post‑baseline echocardiogram. Grade 3 decreased ejection fraction occurred in 3.4% of the 263 patients in the pooled safety population who received Qinlock and who had a baseline and at least one post‑baseline echocardiogram.

In INVICTUS, cardiac dysfunction led to dose discontinuation in 1.2% of the 85 patients who received Qinlock. The safety of Qinlock has not been assessed in patients with a baseline ejection fraction below 50%. Assess ejection fraction by echocardiogram or MUGA scan prior to initiating Qinlock and during treatment, as clinically indicated. Permanently discontinue Qinlock for Grade 3 or 4 left ventricular systolic dysfunction.

Risk of Impaired Wound Healing: Qinlock has the potential to adversely affect wound healing. Withhold Qinlock for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of Qinlock after resolution of wound healing complications has not been established.

Embryo‑Fetal Toxicity: Qinlock can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for at least 1 week after the final dose. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment and for at least 1 week after the final dose. Qinlock may impair fertility in males of reproductive potential.

Adverse Reactions: The most common adverse reactions (≥20%) were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, PPES, and vomiting. The most common Grade 3 or 4 laboratory abnormalities (≥4%) were increased lipase and decreased phosphate.

The safety and effectiveness of Qinlock in pediatric patients have not been established.

Administer strong CYP3A inhibitors with caution. Monitor patients who are administered strong CYP3A inhibitors more frequently for adverse reactions. Avoid concomitant use with strong and moderate CYP3A inducers. If a moderate CYP3A inducer cannot be avoided, increase Qinlock dosing frequency from the recommended dose of 150 mg once daily to 150 mg twice daily during the co‑administration period. If the concomitant moderate CYP3A inducer is discontinued, resume Qinlock dosage back to 150 mg once daily 14 days after the discontinuation of the moderate CYP3A inducer.

To report SUSPECTED ADVERSE REACTIONS, contact Deciphera Pharmaceuticals, LLC, at 1-888-724-3274 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Indication

Qinlock is a kinase inhibitor indicated for the treatment of adult patients with advanced gastrointestinal stromal tumor (GIST) who have received prior treatment with 3 or more kinase inhibitors, including imatinib.

Please see full Prescribing Information, including Patient Information.

Important Safety Information

There are no contraindications for Qinlock.

Palmar‑plantar erythrodysesthesia syndrome (PPES): In INVICTUS, Grade 1–2 PPES occurred in 21% of the 85 patients who received Qinlock. PPES led to dose discontinuation in 1.2% of patients, dose interruption in 2.4% of patients, and dose reduction in 1.2% of patients. Based on severity, withhold Qinlock and then resume at same or reduced dose.

New Primary Cutaneous Malignancies: In INVICTUS, cutaneous squamous cell carcinoma (cuSCC) occurred in 4.7% of the 85 patients who received Qinlock with a median time to event of 4.6 months (range 3.8 to 6 months). In the pooled safety population, cuSCC and keratoacanthoma occurred in 7% and 1.9% of 351 patients, respectively. In INVICTUS, melanoma occurred in 2.4% of the 85 patients who received Qinlock. In the pooled safety population, melanoma occurred in 0.9% of 351 patients. Perform dermatologic evaluations when initiating Qinlock and routinely during treatment. Manage suspicious skin lesions with excision and dermatopathologic evaluation. Continue Qinlock at the same dose.

Hypertension: In INVICTUS, Grade 1–3 hypertension occurred in 14% of the 85 patients who received Qinlock, including Grade 3 hypertension in 7% of patients. Do not initiate Qinlock in patients with uncontrolled hypertension. Monitor blood pressure as clinically indicated. Based on severity, withhold Qinlock and then resume at same or reduced dose or permanently discontinue.

Cardiac Dysfunction: In INVICTUS, cardiac failure occurred in 1.2% of the 85 patients who received Qinlock. In the pooled safety population, cardiac dysfunction (including cardiac failure, acute left ventricular failure, diastolic dysfunction, and ventricular hypertrophy) occurred in 1.7% of 351 patients, including Grade 3 adverse reactions in 1.1% of patients.

In INVICTUS, Grade 3 decreased ejection fraction occurred in 2.6% of the 77 patients who received Qinlock and who had a baseline and at least one post‑baseline echocardiogram. Grade 3 decreased ejection fraction occurred in 3.4% of the 263 patients in the pooled safety population who received Qinlock and who had a baseline and at least one post‑baseline echocardiogram.

In INVICTUS, cardiac dysfunction led to dose discontinuation in 1.2% of the 85 patients who received Qinlock. The safety of Qinlock has not been assessed in patients with a baseline ejection fraction below 50%. Assess ejection fraction by echocardiogram or MUGA scan prior to initiating Qinlock and during treatment, as clinically indicated. Permanently discontinue Qinlock for Grade 3 or 4 left ventricular systolic dysfunction.

Risk of Impaired Wound Healing: Qinlock has the potential to adversely affect wound healing. Withhold Qinlock for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of Qinlock after resolution of wound healing complications has not been established.

Embryo‑Fetal Toxicity: Qinlock can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for at least 1 week after the final dose. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment and for at least 1 week after the final dose. Qinlock may impair fertility in males of reproductive potential.

Adverse Reactions: The most common adverse reactions (≥20%) were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, PPES, and vomiting. The most common Grade 3 or 4 laboratory abnormalities (≥4%) were increased lipase and decreased phosphate.

The safety and effectiveness of Qinlock in pediatric patients have not been established.

Administer strong CYP3A inhibitors with caution. Monitor patients who are administered strong CYP3A inhibitors more frequently for adverse reactions. Avoid concomitant use with strong and moderate CYP3A inducers. If a moderate CYP3A inducer cannot be avoided, increase Qinlock dosing frequency from the recommended dose of 150 mg once daily to 150 mg twice daily during the co‑administration period. If the concomitant moderate CYP3A inducer is discontinued, resume Qinlock dosage back to 150 mg once daily 14 days after the discontinuation of the moderate CYP3A inducer.

To report SUSPECTED ADVERSE REACTIONS, contact Deciphera Pharmaceuticals, LLC, at 1-888-724-3274 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Indication

Qinlock is a kinase inhibitor indicated for the treatment of adult patients with advanced gastrointestinal stromal tumor (GIST) who have received prior treatment with 3 or more kinase inhibitors, including imatinib.

Please see full Prescribing Information, including Patient Information.