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.

 

Qinlock Clinical Presentation with Neeta Somaiah, MD

Explore the current state of advanced GIST with Neeta Somaiah, MD, from the MD Anderson Cancer Center in Houston, TX, as she presents clinical evidence supporting the use of QINLOCK.

Welcome to this presentation of Qinlock (ripretinib) for the treatment of Advanced Gastrointestinal Stromal Tumor. Qinlock is indicated for the treatment of adult patients with advanced gastrointestinal stromal tumor or GIST, who have received prior treatment with three or more kinase inhibitors, including imatinib.

Well, my name is Neeta Somaiah. I'm a medical oncologist at MD Anderson Cancer Center in Houston, Texas. My current role is an Associate Professor and Deputy Chair of the Department of Sarcoma. I trained at Fox Chase Cancer Center in Philadelphia, and have over 10 years of experience in treating sarcomas. I have been involved in the early development and the clinical trial that led to the approval of Qinlock in GIST.

In this program, we're going to review the current state of GIST, the Qinlock mechanism of action, efficacy and safety of Qinlock, important safety information, the dosing and administration of Qinlock, and patient management and some other considerations. And then we will summarize the data in the end.

What's the current state of gastrointestinal stromal tumor? We will review the key epidemiology and origins of GIST, discuss how diagnosis and treatment has evolved over the past few decades, and review the key drivers of GIST, progression, and drug resistance. And we will highlight the unmet clinical needs for patients.

So GIST is the most common sarcoma of the GI tract. There are around 4000 to 6000 new cases of GIST per year. And it is most common in individuals aged 50 to 80 years with equal incidence in men and women. The most common site of origin is the stomach. And next most common is the small intestine, with jejunum and ileum, followed by the duodenum.

Here we're going to look at how the treatment of GIST has evolved over the past decades. GIST was recognized in the early 1980s where surgery was the only treatment and chemotherapy really had no role or was not effective in the treatment of GIST. In the 1990s, it was discovered that staining specific biomarkers, such as CD117 known as KIT or DOG1, was diagnostic and helped confirm the diagnosis of GIST. Soon after, it was discovered that there were specific oncogenic drivers such as in KIT and PDGFRA that were discovered in GIST. And this kind of led to the era of the 2000s where soon after TKIs or tyrosine kinase inhibitors with activity against KIT and PDGFRA was tested in GIST and led to the approval of the few tyrosine kinase inhibitors currently in use, starting with imatinib.

So KIT and PDGFRA mutations are the drivers in approximately 85% of GIST. The majority of GIST harbor in activating mutation in KIT and this most often is an Exon 11, followed by Exon 9. A minority of GIST patients have PDGFRA mutations found in around 5% to 10% of GIST, of which Exon 18 (D842V) is the most common. 10% to 15% of GIST are without known KIT or PDGFRA mutations, and often referred to as wild type, but basically wild type for KIT or PDGFRA. In these patients, the most common are mutations in SDH complex. We also find mutations in NF‑1, BRAF, KRAS, and NTRK3 fusions in rare cases.

The vast majority of patients who benefit from frontline tyrosine kinase inhibitor treatment will eventually develop resistance. So what we see is patients on frontline therapy will have a median progression free survival of around 18.9 months with around a 50% response rate. But after failure of frontline TKI, patients will progress, and progression can be in either a limited fashion where they develop nodular or focal progression or a nodule within a mass that is progressing, or the progression can be more widespread. The goal of treatment in advanced GIST is the control of disease progression. A long‑term follow‑up study did show a correlation between disease control, including stable disease, and long‑term survival.

Advanced GIST is marked by the development of secondary drug‑resistance mutations, which play a key role in disease progression. In GIST, there is extensive mutational heterogeneity that drives resistance to establish therapies. The development of these secondary drug‑resistant mutations play a key role in disease progression. As shown in the figure on the left, broad inter‑ and intratumor heterogeneity exist among secondary resistance mutations, whereby a single patient may have multiple mutations within or between tumors. These secondary mutations are most common in Exon 13 and 17 when they have a primary mutation in KIT, or in Exon 18 in the PDGFRA gene when the primary mutation is in PDGFRA. Therefore, there is a need for broad‑spectrum inhibition of the many mutations that fuel resistance and progression in GIST.

Patients with resistant GIST tend to progress quickly through second‑ and third‑line therapies. As we discussed, patients will derive the maximum benefit or at least majority patients will derive maximum benefit on imatinib, but thereafter, the median progression free survival on second‑line therapy is around 5.6 months with a response rate of 6.8% with sunitinib, and in third‑line therapy, the median progression free survival is 4.8 months with the response rate of around 4.5%. And until recently, there were no approved therapies for fourth‑line GIST. Avapritinib is approved for the treatment of unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, which we discussed, was present around 5% to 6% of patients. And this mutation tends to be resistance to the prior approved lines of tyrosine kinase inhibitor therapy. Could a novel therapeutic approach help address the challenge of drug resistance in advanced GIST?

Break through resistance with Qinlock. Qinlock is a novel, switch‑control kinase inhibitor for the treatment of patients with advanced GIST. It is indicated for the treatment of adult patients with advanced GIST who have received prior treatment with three or more kinase inhibitors, including imatinib. All through the presentation, we will review some important safety information, including the palmar‑plantar erythrodysesthesia syndrome, which we will discuss in depth later.

So we will now be talking about the mechanism of action of Qinlock. Qinlock is the first TKI designed specifically for GIST, and it was engineered to block the drivers of resistance in advanced GIST. Qinlock is a novel switch‑control kinase inhibitor that provides broad‑spectrum inhibition of KIT and PDGFRA kinase signaling in vitro through a dual mechanism of action. Now kinase activation requires interaction of two critical regions, the activation switch, and the switch pocket. As shown in preclinical studies, Qinlock binds to both the activation switch and the switch pocket, regardless of where mutations arise. And it locks the kinase in the inactive or off state, inhibiting downstream signaling and cancer cell proliferation. In preclinical studies, this dual mechanism provided broad‑spectrum inhibition of KIT and PDGFRA kinase activity, including multiple primary mutations, multiple secondary mutations, and even wild type GIST. We will now be looking at a video that nicely explains this mechanism of action.

How Qinlock works. Gastrointestinal stromal tumor or GIST is often driven by primary activating mutations in kinase genes KIT and PDGFRA. 70% to 80% of GIST have mutations in one or more regions or exons of the KIT gene. 5% to 10% of GIST have mutations in the PDGFRA gene, and 10% to 15% of GIST are without mutations in KIT or PDGFRA genes. These are often referred to as wild type. Kinase activation requires the interaction of two critical regions, the activation switch, and the switch pocket. Mutations in the 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 up regulation of kinase signaling which drives cancer cell proliferation and/or survival. As secondary drug resistance mutations emerge, some tyrosine kinase inhibitors may lose their ability to prevent kinase activation leading to cancer cell proliferation, otherwise known as drug resistance. Complicating treatment even further, following failure of frontline TKI therapy, GIST patients often have multiple tumors each of which can be driven by different secondary mutations.

The Qinlock mechanism of action. Qinlock is a novel switch‑control kinase inhibitor that provides broad‑spectrum inhibition of KIT and PDGFRA kinase signaling in vitro through a dual mechanism of action. As shown in preclinical studies, 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.

Now moving on to the efficacy and safety of Qinlock. Qinlock was studied in INVICTUS, a global, multicenter, randomized, double‑blind placebo‑controlled Phase 3 trial in 129 patients who had received more than equal to three prior anticancer therapies for advanced GIST. Patients who were randomized in a two is to one fashion to receive Qinlock 150 milligrams once daily, or placebo. It was 85 patients on Qinlock and 44 patients on placebo. And at the time of disease progression, patients on Qinlock were allowed to either continue on open‑label Qinlock at 150 milligrams once daily if the investigator thought the patient was benefiting, or escalates to 150 milligrams BID, or discontinue drug treatment. Patients on placebo were allowed to cross over at disease progression, and they cross over to open‑label Qinlock 150 milligrams once daily, or if they so chose to discontinue study treatment.

The primary endpoint was progression free survival based on disease assessment by blinded independent central review of radiology using the modified RECIST 1.1 criteria. The secondary endpoints included objective response rate based on disease assessment by the blinded independent central radiology, and also overall survival, quality of life, and safety.

A wide range of advanced GIST patients were enrolled in the INVICTUS study, and it was a heavily pretreated cohort that is representative of patients in the fourth line setting and beyond. Between 60% to 64% of patients had three prior therapies, and 36% to 39% of patients had between four to seven prior therapies. Patient characteristics reflect, as we said, a real world fourth line GIST population, and were generally well balanced between Qinlock and placebo. INVICTUS included patients with ECOG performance status of zero to two, and enrolled patients regardless of their mutational status.

Qinlock demonstrated a powerful PFS benefit in INVICTUS. The median progression free survival was superior with Qinlock, 6.3 months, versus one month for placebo. There was an 85% risk reduction of progression or death versus placebo. And the hazard ratio was 0.15. This result was highly significant and the separation of the two curves was dramatic and occurred quickly.

In addition to the median progression free survival and the hazard ratio or risk reduction, looking at the estimated landmark PFS at clinically relevant time points helps to further characterize the progression free survival data from the Kaplan‑Meier curve. The estimated landmark PFS at nine months was over 34% for Qinlock, and not estimatable for placebo. The estimated landmark PFS at 12 months or one year was 21% with Qinlock, and not estimatable for placebo. Furthermore, Qinlock PFS results were generally consistent across the assessed patient subgroups.

Qinlock was associated with clinically meaningful survival outcomes. The median overall survival was 15.1 months with Qinlock versus 6.6 months with placebo. This resulted in a 64% reduction in the risk of death versus placebo, with a hazard ratio of 0.36. This analysis includes patients originally randomized to placebo who crossed over to receive open‑label Qinlock as well. This data is clinically meaningful as one could see the early and sustained separation of the Kaplan‑Meier curves.

Overall survival was not evaluated for statistical significance as a result of the sequential testing procedure for the secondary endpoints of overall response rate and overall survival as prespecified in the statistical analysis. The confirmed overall response rate by blinded independent central review was 9.4% with Qinlock versus 0% with placebo. The P value was 0.0504 narrowly missing the statistical significance. The median duration of response had not been reached by the study cutoff date. However, nearly an additional two‑thirds of patients treated with Qinlock experienced stable disease lasting greater than six weeks versus 20.5% with placebo. The overall response rate is encouraging in a heavily pretreated patient population that progressed in multiple prior therapies. A confirmed objective response represents a greater than 30% reduction in tumor size.

When patients who were originally randomized to placebo and crossed over to Qinlock are separated out from the patients who did not cross over, we see that patients who were originally randomized to placebo and crossed over to receive Qinlock had a median overall survival of 11.6 months, and patients who did not cross over to receive Qinlock had a median overall survival of 1.8 months. Approximately 66% of patients originally randomized to placebo crossed over to receive open‑label Qinlock.

The safety of Qinlock, or ripretinib, was established across a broad range of patients in the INVICTUS trial. The most common serious adverse reactions were abdominal pain, anemia, nausea, and vomiting. The rates of dose modifications due to adverse reactions were similar between Qinlock and placebo. Dose interruptions were similar, 24% for Qinlock, and 21% for placebo. Dose reductions were rare, 7% for Qinlock, and 2% for placebo. There was a lower rate of discontinuation with Qinlock versus placebo.

The overall rates of Grade 3/4 adverse reactions were similar between Qinlock and placebo. The most common adverse reactions were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar‑plantar erythrodysesthesia, and vomiting. When you look at the rates, the alopecia rate was 52% in Qinlock versus 4.7% in placebo. And when you look at fatigue, the Grade 3‑4 toxicity was 3.5% with Qinlock, and 2.3% with placebo. And the abdominal pain was 7% for Grade 3‑4 toxicity with Qinlock versus 4.7% with placebo. The most common Grade 3 or 4 lab abnormalities were increased lipase and decreased phosphate. There were no Grade 4 laboratory abnormalities.

Clinically relevant differences were observed between Qinlock and placebo in prespecified quality of life assessments. PRO assessments were analyzed comparing changes from Cycle 1 Day 1 at baseline and Cycle 2 Day 1 between Qinlock and placebo. Comparisons were only made out to Cycle 2 Day 1 for Qinlock and placebo in patients with completed PRO assessments due to a low number of placebo patients after this point. The minimally important clinical difference has been defined as a greater than 10% mean score change, or a 5‑point change. The self‑reported health was assessed using EQ‑5D‑5L, the visual analog scale. In all this, the self‑reported health remains stable with Qinlock compared to a decrease with placebo. The physical function was assessed using the EORTC QLQ‑C30 physical function, and showed the physical function remains stable with Qinlock compared to a decrease with placebo. The role function was also assessed using the EORTC QLC‑C30 role function, and this showed that role function remains stable with Qinlock compared to a decrease with placebo.

Now moving on to important safety information and more details about it. So for the skin‑related toxicities... palmar‑plantar erythrodysesthesia syndrome or PPES. In the INVICTUS study, Grade 1‑2 PPES occurred in 21% of the 85 patients who received Qinlock. This led to a dose discontinuation in 1.2% of patients, dose interruption in 2.4% of patients, and a dose reduction in 1.2% of patients. And so based on this, if patients do have severe symptoms or severe PPES, you can withhold Qinlock, and then resume at the same or reduced dose based on their time to recovery.

With regards to primary cutaneous malignancies, on INVICTUS, cutaneous squamous cell carcinomas were reported in four patients, that is 4.7%, of the 85 patients who received Qinlock with a median time to event of 4.6 months ranging from 3.8 to 6 months. Melanoma was reported in two patients, which is 2.4%, who received Qinlock.

In the pooled safety population, the cutaneous squamous cell carcinoma and keratoacanthoma was reported in 7% and 1.9% of the 351 patients, respectively. Melanoma was reported in 0.9% of the 351 patients.

It's important to perform dermatologic evaluations when initiating Qinlock and routinely during treatment. And you manage suspicious skin lesions with excision and dermatopathologic evaluation, but you can continue treatment at the same dose thereafter.

With regards to hypertension in the INVICTUS study, Grade 1‑3 hypertension occurred in 14% of patients who received Qinlock, including Grade 3 hypertension in 7% of patients. Do not initiate Qinlock in patients with uncontrolled hypertension. You must monitor blood pressure as clinically indicated. And based on severity, withhold Qinlock and then resume at the same or reduced dose.

Cardiac dysfunction, including cardiac failure, acute left ventricular failure, diastolic dysfunction, and ventricular hypertrophy, was also monitored. On the INVICTUS study, cardiac failure occurred in one, which is 1.2%, of the 85 patients who received Qinlock. Grade 3 decreased ejection fraction was reported in two patients of the 77 patients who received Qinlock and who had a baseline and post baseline echocardiogram, so that was 2.6%. Cardiac dysfunction led to dose discontinuation in 1.2% of the patients. In the pooled safety population, cardiac dysfunction was reported in 1.7% of the 351 patients, including Grade 3 adverse reactions in 1.1% of patients. Grade 3 decreased ejection fraction was reported in 3.4% of the 263 patients who had baseline and post baseline echocardiograms. The safety of Qinlock has not been assessed in patients with a baseline ejection fraction below 50%. As clinically indicated, assess ejection fraction by echocardiogram or MUGA scan prior to initiating Qinlock and during treatment. Permanently discontinue Qinlock for Grade 3 or 4 left ventricular systolic dysfunction.

With regards to risk of impaired wound healing, Qinlock has the potential to adversely affect wound healing, so you must withhold Qinlock for at least one week prior to elective surgery. Do not administer for at least two weeks following major surgery and until adequate wound healing. The safety of resumption of Qinlock after resolution of the wound healing complications has not been established.

Qinlock can cause fetal harm when administered to a pregnant woman. Advise pregnant females of the potential risk to a fetus. Advise females of reproductive potential and meals with female partners of reproductive potential to use effective contraception during treatment and for at least one 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 one week after the final dose. Qinlock may impair fertility in males of reproductive potential as well. The safety and effectiveness of Qinlock in pediatric patients has 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 CYP3A inducers.

Moving on to the dosing and administration of Qinlock. Qinlock 150 milligrams is administered as three 50 milligram tablets orally once daily. This can be taken with or without food. Instruct patients to swallow tablets whole, and advise patients to take Qinlock at the same time each day. If patients missed a dose in less than eight hours of their prescribed time, they can redose, otherwise, skip the dose and just take the next scheduled dose. Advise patients to not take additional doses if vomiting occurs after taking Qinlock and to just continue with their next scheduled dose.

Dose Qinlock with confidence as most Qinlock‑treated patients are able to start and stay on the full indicated dose. Over 90% of patients treated with Qinlock did not experience a dose reduction or discontinuation due to adverse reactions. 13 out of 14 patients did not dose reduce due to an adverse reaction. And 11 out of 12 patients did not discontinue due to an adverse reaction. Rates of dose interruptions were similar between Qinlock and placebo. Mutational testing is not required prior to administration of Qinlock. However, molecular profiling is recommended for good clinical practice.

It is important while managing patients on Qinlock to set expectations because this sets patients up for success. Advise patients that adverse reactions may occur while taking Qinlock, and encourage patients and care partners to tell you about any adverse reactions the patients may experience. Review the management recommendations of select adverse reactions with your patients. The full dose modification recommendations for adverse reactions, such as PPES, hypertension, left ventricular systolic dysfunction, arthralgia or myalgia, and other Grade 3 or 4 adverse reactions are contained in the full Prescribing information in Table 1 and also in the appendix of this presentation.

Now we'll talk about considerations for patients with advanced GIST. Qinlock is indicated for adult patients who have been diagnosed with advanced GIST and have received three or more prior TKIs, including imatinib. Qinlock has indicated regardless of the mutational status, the sequence of the prior TKIs, evidence of progression, or ECOG performance status.

Moving on to the summary and conclusions. Qinlock is a novel treatment that provides a powerful PFS benefit for patients with advanced GIST. The median progression free survival was 6.3 months on Qinlock versus one month on placebo, representing an 85% risk reduction of progression or death versus placebo. The hazard ratio is 0.15 with the P value of less than 0.0001. The median overall survival was 15.1 months on Qinlock versus 6.6 months with placebo, representing a 64% risk reduction of death versus placebo. The overall response rate, which was a key secondary endpoint, was 9.4% with Qinlock versus 0% with placebo. A P value of 0.0504. Most patients are able to start and stay on the full indicated dose, so dose Qinlock with confidence. 93% did not have their dose reduced due to an adverse reaction. And 92% did not discontinue Qinlock due to an adverse reaction. Mutational testing is not required to administer Qinlock.

The most common serious adverse reactions observed in Qinlock‑treated patients in more than 2% of patients were abdominal pain, anemia, nausea, and vomiting. The most common adverse reactions in more than equal to 20% of patients were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar‑plantar erythrodysesthesia, and vomiting. The most common Grade 3‑4 lab abnormalities included increased lipase and decreased phosphate.

Thank you for your attention and listening to this presentation. If you have any other questions or need more information, please contact your Deciphera representative.

 

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Reference: 1. QINLOCK [package insert]. Waltham, MA: Deciphera Pharmaceuticals, Inc; 2020.


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 CYP3A inducers.

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 CYP3A inducers.

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.