DailyMed Label: QINLOCK

DailyMed Label: QINLOCK

2023

DailyMed Prescription

QINLOCK

Ripretinib

Deciphera Pharmaceuticals, LLC

NDC: 73207-101

NDC: 73207-101

Ripretinib is a kinase inhibitor. The chemical name of ripretinib is 1-(4-bromo-5-[1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl]-2-fluorophenyl)-3-phenylurea. The molecular formula is C 24 H 21 BrFN 5 O 2 and the molecular weight is 510.36 g/mol. The chemical structure of ripretinib is shown below: Ripretinib is a white to off-white crystalline solid. Ripretinib is a lipophilic, weak base, and practically insoluble in aqueous media. QINLOCK is available as a white to off-white, oval tablets for oral use containing 50 mg of ripretinib. The tablet is debossed with “DC1” on one side. Each tablet contains the following inactive ingredients: crospovidone, hypromellose acetate succinate, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and silicon dioxide. Figure

QINLOCK is 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. 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 )

Recommended Dosage : 150 mg orally once daily with or without food. ( 2.1 ) The recommended dosage of QINLOCK is 150 mg orally once daily with or without food until disease progression or unacceptable toxicity. Instruct patients to swallow tablets whole. Advise patients to take QINLOCK at the same time each day. Advise patients to take a missed dose if less than 8 hours have passed since the missed scheduled dose. Advise patients not to take an additional dose if vomiting occurs after taking QINLOCK and to continue with their next scheduled dose. The recommended dose reduction for adverse reactions is: QINLOCK 100 mg orally once daily. Permanently discontinue QINLOCK in patients who are unable to tolerate 100 mg orally once daily. The recommended dosage modifications of QINLOCK for adverse reactions are provided in Table 1 . Table 1: Recommended Dosage Modifications for QINLOCK for Adverse Reactions Adverse Reaction Severity a QINLOCK Dosage Modifications a Graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE v4.03). Palmar-Plantar Erythrodysesthesia Syndrome (PPES) [see Warnings and Precautions ( 5.1 )] Grade 2 Withhold QINLOCK until Grade ≤1 or baseline. If recovered within 7 days, resume QINLOCK at same dose; otherwise resume at reduced dose. Consider re-escalating QINLOCK if maintained at Grade ≤1 or baseline for at least 28 days. If PPES recurs, withhold QINLOCK until Grade ≤1 or baseline and then resume QINLOCK at a reduced dose regardless of time to improvement. Grade 3 Withhold QINLOCK for at least 7 days or until Grade ≤1 or baseline (maximum 28 days). Resume QINLOCK at a reduced dose. Consider re-escalating QINLOCK if maintained at Grade ≤1 or baseline for at least 28 days. Hypertension [see Warnings and Precautions ( 5.3 )] Grade 3 If symptomatic, withhold QINLOCK until symptoms have resolved and blood pressure is controlled. If blood pressure is controlled to Grade ≤1 or baseline, resume QINLOCK at the same dose; otherwise, resume QINLOCK at reduced dose. If Grade 3 hypertension recurs, withhold QINLOCK until symptoms have resolved and blood pressure is controlled. Resume QINLOCK at a reduced dose. Grade 4 Permanently discontinue QINLOCK. Left Ventricular Systolic Dysfunction [see Warnings and Precautions ( 5.4 )] Grade 3 or 4 Permanently discontinue QINLOCK. Arthralgia or Myalgia [see Adverse Reactions ( 6.1 )] Grade 2 Withhold QINLOCK until Grade ≤1 or baseline. If recovered within 7 days, resume QINLOCK at same dose; otherwise resume QINLOCK at reduced dose. Consider re-escalating QINLOCK if maintained at Grade ≤1 or baseline for at least 28 days. If arthralgia or myalgia recurs, withhold QINLOCK until Grade ≤1 or baseline and then resume QINLOCK at a reduced dose regardless of time to improvement. Grade 3 Withhold QINLOCK for at least 7 days or until Grade ≤1 or baseline (maximum of 28 days). Resume QINLOCK at a reduced dose. Consider re-escalating QINLOCK if maintained at Grade ≤1 or baseline for at least 28 days. Other Adverse Reactions [see Adverse Reactions ( 6.1 )] Grade 3 or 4 Withhold QINLOCK until Grade ≤1 or baseline (maximum 28 days), and then resume QINLOCK at a reduced dose; otherwise permanently discontinue. Consider re-escalating QINLOCK if no recurrence of the adverse reaction for at least 28 days. If Grade 3 or 4 recurs, permanently discontinue QINLOCK. Avoid concomitant use of moderate CYP3A inducers during QINLOCK treatment. If a moderate CYP3A inducer cannot be avoided, increase the QINLOCK dosing frequency from the recommended dose of 150 mg once daily to 150 mg twice daily during the co-administration period. Monitor for clinical response and tolerability. 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  [see Drug Interactions ( 7.1 ) and Clinical Pharmacology ( 12.3 )] . For patients concomitantly using a moderate CYP3A inducer with QINLOCK (taking QINLOCK twice daily) who missed a dose: If less than 4 hours have passed since the missed scheduled dose, advise the patient to take the missed dose as soon as possible and then take the next dose at the regularly scheduled time. If more than 4 hours have passed since the missed scheduled dose, advise the patient to skip the missed dose and then take the next dose at the regularly scheduled time. [see Drug Interactions ( 7.1 )] .

Tablets: 50 mg, white to off-white, oval shaped, debossed with “DC1” on one side. Tablets: 50 mg. ( 3 )

None. None. ( 4 )

Palmar-Plantar Erythrodysesthesia Syndrome : Based on severity, withhold QINLOCK and resume at same or reduced dose. ( 2.2 , 5.1 ) New Primary Cutaneous Malignancies : Perform dermatologic evaluations when initiating QINLOCK and routinely during treatment. ( 5.2 ) Hypertension : Do not initiate QINLOCK in patients with uncontrolled hypertension and monitor blood pressure during treatment. Based on severity, withhold QINLOCK and then resume at same or reduced dose or permanently discontinue. ( 2.2 , 5.3 ) Cardiac Dysfunction : 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. ( 2.2 , 5.4 ) Risk of Impaired Wound Healing : Withhold QINLOCK for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks after major surgery and until adequate wound healing. The safety of resumption of QINLOCK after resolution of wound healing complications has not been established. ( 5.5 ) Photosensitivity : May cause photosensitivity reactions. Advise patients to limit direct ultraviolet exposure. ( 5.6 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.7 ,  8.1 ,  8.3 ) In INVICTUS, Grade 1-2 palmar-plantar erythrodysesthesia syndrome (PPES) occurred in 21% of the 85 patients who received QINLOCK [see Adverse Reactions ( 6.1 )]. 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 [see Dosage and Administration ( 2.2 )] . 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 patients, respectively. In INVICTUS, melanoma occurred in 2.4% of the 85 of patients who received QINLOCK. In the pooled safety population, melanoma occurred in 0.9% of 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. In INVICTUS, Grade 1-3 hypertension occurred in 14% of the 85 patients who received QINLOCK, including Grade 3 hypertension in 7% [see Adverse Reactions ( 6.1 )] . Do not initiate QINLOCK in patients with uncontrolled hypertension. Adequately control blood pressure prior to initiating QINLOCK. Monitor blood pressure as clinically indicated during treatment with QINLOCK, and initiate or adjust antihypertensive therapy as appropriate. Based on severity, withhold QINLOCK and then resume at same or reduced dose or permanently discontinue [see Dosage and Administration ( 2.2 )] . 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 patients, including Grade 3 adverse reactions in 1.1%. 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. In the pooled safety population, Grade 3 decreased ejection fraction occurred in 3.4% of the 263 patients 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 [see Dosage and Administration ( 2.2 )] . Impaired wound healing complications can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. Therefore, 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. QINLOCK may cause photosensitivity reactions. In all patients treated with QINLOCK in clinical trials (n=621), photosensitivity reactions occurred in 0.6% of patients. Advise patients to limit direct ultraviolet exposure during treatment with QINLOCK and for at least one week after discontinuation of treatment. Based on findings from animal studies and its mechanism of action, QINLOCK can cause fetal harm when administered to a pregnant woman. Oral administration of ripretinib to pregnant rats and rabbits during the period of organogenesis resulted in malformations primarily associated with the cardiovascular and skeletal systems, anatomic variations, decreased fetal body weight, and increased post-implantation loss at exposures approximately one half of the recommended dose of 150 mg once daily based on area under the curve (AUC). Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with QINLOCK and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with QINLOCK and for 1 week after the last dose [see Use in Specific Populations ( 8.1 , 8.3 ), Nonclinical Toxicology ( 13.1 )].

The following clinically significant adverse reactions are discussed elsewhere in the labeling:

Strong CYP3A Inhibitors : Monitor more frequently for adverse reactions. ( 7.1 ) Strong CYP3A Inducers : Avoid concomitant use of strong CYP3A inducers. ( 7.1 ) Moderate CYP3A Inducers : Avoid concomitant use of moderate CYP3A inducers. If a moderate CYP inducer cannot be avoided, increase ripretinib dose frequency to twice daily. ( 2.3 , 7.1 ) Table 4 includes drug interactions that affect the pharmacokinetics of ripretinib. Table 4: Drug Interactions that Affect QINLOCK Strong CYP3A Inhibitors Clinical Impact Coadministration of QINLOCK with a strong CYP3A inhibitor increased the exposure of ripretinib and its active metabolite (DP-5439), which may increase the risk of adverse reactions [see Clinical Pharmacology ( 12.3 )]. Prevention or Management Monitor patients more frequently for adverse reactions. Strong and Moderate CYP3A Inducers Clinical Impact Coadministration of QINLOCK with a strong CYP3A inducer decreased the exposure of ripretinib and its active metabolite (DP-5439), which may decrease QINLOCK anti-tumor activity [see Clinical Pharmacology ( 12.3 )] . Coadministration of QINLOCK with moderate CYP3A inducers is predicted to decrease the exposure of ripretinib and its active metabolite (DP-5439), which may decrease QINLOCK anti-tumor activity [see Clinical Pharmacology ( 12.3 )] . Prevention or Management Avoid concomitant use of QINLOCK with strong CYP3A inducers. Avoid concomitant use of QINLOCK with 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. Monitor for clinical response and tolerability [see Dosage and Administration ( 2.3 )] .

Lactation : Advise not to breastfeed. ( 8.2 ) Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology ( 12.1 )] , QINLOCK can cause fetal harm when administered to a pregnant woman. There are no available data on the use of QINLOCK in pregnant women to inform a drug-associated risk. Administration of ripretinib to pregnant rats and rabbits during the period of organogenesis resulted in malformations primarily associated with the cardiovascular and skeletal systems, anatomic variations, reduced fetal body weight, and increased post-implantation loss at maternal exposures that were approximately equal to the human exposure at the recommended dose of 150 mg (see  Data ). Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In an embryo-fetal development study investigating daily doses of ripretinib administered during the period of organogenesis in rats, ripretinib resulted in malformations primarily associated with the cardiovascular and skeletal systems, including interrupted or retroesophageal aortic arch and retroesophageal subclavian artery, fusion of the exoccipital bone to the first cervical vertebra, branched and fused ribs, anomalies of the cervical, thoracic, caudal, and sacral vertebrae, absent forepaw phalanges, and absent metacarpals at a dose of 20 mg/kg/day (approximately one half of the human exposure at the recommended dose of 150 mg). An increased incidence of anatomic variations were also observed at 20 mg/kg/day. Variations included malpositioned carotid and subclavian artery origins, malpositioned subclavian artery, absent or elongated innominate artery, misshapen and nodulated ribs, bipartite, incompletely ossified, or unossified vertebral centra, small or misshapen vertebral arches, and reductions in ossified forelimb and hindlimb phalanges, hindlimb metatarsals, and caudal vertebrae. In a preliminary embryo-fetal development study investigating the administration of ripretinib in rabbits during the period of organogenesis, ripretinib resulted in total loss of pregnancy at doses of 150 mg/kg (approximately 3.5 times the human exposure at the recommended dose of 150 mg). At a dose of 40 mg/kg (approximately 2.1 times the human exposure at the recommended dose of 150 mg), toxicities included increased post-implantation loss and decreased fetal body weights. Risk Summary There are no data regarding the presence of ripretinib or its metabolites in either human milk or its effects on a breastfed child or on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with QINLOCK and for 1 week after the last dose. QINLOCK can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1 )] . Pregnancy Testing Verify pregnancy status of females of reproductive potential prior to the initiation of QINLOCK  [see Use in Specific Populations ( 8.1 )] . Contraception Females Advise females of reproductive potential to use effective contraception during treatment and for 1 week after the last dose. Males Advise males with female partners of reproductive potential to use effective contraception during treatment and for 1 week after the last dose. Infertility Based on findings from animal studies, QINLOCK may impair fertility in males of reproductive potential [see Nonclinical Toxicology ( 13.1 )] . The safety and effectiveness of QINLOCK in pediatric patients have not been established. Animal Toxicity Data In 13-week repeat-dose studies in rats there were dose-dependent findings of increased osteoblastic surface and decreased trabeculae of the femur at doses ≥30 mg/kg/day (approximately one half of the human exposure at the recommended dose of 150 mg). There were additional findings of missing or discolored teeth that were accompanied by dose-dependent incisor degeneration at doses ≥30 mg/kg/day. Of the 85 patients in INVICTUS who received QINLOCK 150 mg orally once daily, 24% were between 65 to 74 years of age and 9% were 75 years of age or older. Clinical studies of QINLOCK did not include sufficient numbers of patients aged 65 and older to determine whether they respond differently from younger patients. No dose adjustment is recommended in patients with hepatic impairment (Child-Pugh A, B, or C) [see Clinical Pharmacology ( 12.3 )] .

QINLOCK 50 mg tablets are white to off-white, oval shaped, and debossed with “DC1” on one side.   90-count bottles            NDC 73207-101-30 Dispense in original container only. Store in the original container with the desiccant to protect from moisture and light. Replace cap securely each time after opening. Do not discard desiccant. Store at 20°C to 25°C (68°F to 77°F); excursion permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature] .

Ripretinib is a tyrosine kinase inhibitor that inhibits KIT proto-oncogene receptor tyrosine kinase (KIT) and platelet derived growth factor receptor A (PDGFRA) kinase, including wild type, primary, and secondary mutations. Ripretinib also inhibits other kinases in vitro, such as PDGFRB, TIE2, VEGFR2, and BRAF. Exposure-Response Relationships Ripretinib exposure-response relationships and the time course of pharmacodynamics have not been fully characterized. Cardiac Electrophysiology No large mean increase in QTc interval (i.e. >20 ms) was detected following treatment with QINLOCK at the recommended dose of 150 mg taken orally once daily. The pharmacokinetics of ripretinib and its equally active metabolite (DP-5439) were characterized in clinical studies. In patients with advanced malignancies, ripretinib AUC 0-24h increased proportionally over a dose range of 20-250 mg (0.13 to 1.67 times the recommended dose), but C max was less than dose proportional; DP-5439 C max and AUC 0-24h were less than dose proportional within the dose range of 50-250 mg (0.33 to 1.67 times the recommended dose). No clinically significant differences in the C max and AUC 0-24h were observed between administration of QINLOCK with a high-fat meal (150, 250, and 500-600 calories from protein, carbohydrate, and fat, respectively) and under fasted conditions. The pharmacokinetic parameters of ripretinib and DP-5439 are summarized in Table 5 . Table 5: Pharmacokinetic Parameters of Ripretinib and DP-5439 a. Estimated based on cycle 1, day 15 b. After a single oral dose of 150 mg CV=coefficient of variation; C max =maximum plasma concentration; AUC 0-12h =area under the plasma concentration-time curve from time zero to 12 hours; AUC 0-24h =area under the plasma concentration-time curve from time zero to 24 hours; T max =time to maximum concentration Parameter Ripretinib DP-5439 General Information Steady state exposure following QINLOCK 150 mg once daily [Mean (CV%)] C max (ng/mL) 761 (32) 804 (46) AUC 0-12h (ng•h/mL) 5678 (32) 7138 (44) Time to steady state [Days] 14 14 Accumulation ratio (AUC 0-12h ) [Mean (CV%)] a 1.7 (55) 5.29 (49) Absorption T max [Median in hours] b 4 15.6 Distribution Plasma protein binding (in vitro) Human serum albumin 99.8% 99.7% α-1 acid glycoprotein 99.4% >99.8% Steady state apparent volume of distribution, L [Mean (CV%)] b 307 (39) 507 (51) Elimination Apparent clearance, L/hr [Mean (CV%)] b 15.3 (45) 17.5 (63) Half-life, hours [Mean (CV%)] b 14.8 (30) 17.8 (23) Metabolism Metabolic pathways Major CYP3A4 CYP3A4 Minor CYP2C8 and CYP2D6 CYP2C8, CYP2E1 and CYP2D6 Excretion Excretion pathways Feces 34% 6% Urine 0.02% 0.1% Specific Populations No clinically significant differences in the pharmacokinetics of ripretinib were observed based on age (19 to 87 years), sex, race (White, Black, and Asian), body weight (39 to 138 kg), tumor (GIST or other solid tumors), prior gastrectomy, mild to moderate renal impairment (CLcr 30 to <90 mL/min estimated by Cockcroft-Gault), and mild hepatic impairment (total bilirubin ≤ULN and AST >ULN or total bilirubin 1 to 1.5 × ULN and AST any). The effects of severe renal impairment (CLcr 15 to 29 mL/min) on the pharmacokinetics of ripretinib have not been studied. Patients with Hepatic Impairment In subjects with mild hepatic impairment, there were no clinically significant changes in AUC 0-last and C max when compared to matched healthy subjects. In subjects with moderate hepatic impairment, ripretinib AUC 0-last increased 2-fold while C max was unchanged when compared to matched healthy subjects. The combined AUC 0-last of ripretinib and DP-5439 increased 1.5-fold. In subjects with severe hepatic impairment, ripretinib AUC 0-last increased 2.6-fold and C max decreased by 24% when compared to matched healthy subjects. The combined AUC 0-last of ripretinib and DP-5439 increased by 1.4-fold. The observed magnitude of increase in ripretinib and the combination of ripretinib and DP-5439 exposures in subjects with hepatic impairment is unlikely to be clinically relevant based on the known safety profile of ripretinib. Drug Interaction Studies Clinical Studies and Model-Informed Approaches Strong CYP3A Inhibitors: Coadministration of QINLOCK with itraconazole (a strong CYP3A inhibitor and also a P-gp inhibitor) increased ripretinib C max by 36% and AUC 0-inf by 99% and also increased DP-5439 AUC 0-inf by 99% with no change in its C max . Strong CYP3A Inducers: Coadministration of QINLOCK with rifampin (a strong CYP3A inducer) decreased ripretinib C max by 18% and AUC 0-inf by 61% and also decreased DP-5439 AUC 0-inf by 57% with increased C max by 37%. Moderate CYP3A Inducers: Coadministration of QINLOCK with efavirenz (a moderate CYP3A inducer) was predicted to decrease ripretinib C max by 24% and decrease AUC 0-inf by 56%. Proton Pump Inhibitors: No clinically significant differences in the plasma exposure to ripretinib and DP-5439 were observed when QINLOCK was coadministered with pantoprazole (a proton pump inhibitor). In Vitro Studies CYP Enzymes: Ripretinib and DP-5439 are inhibitors of CYP2C8. Ripretinib and DP-5439 are not inducers of CYP1A2, CYP2B6, or CYP3A4. Transporter Systems: Ripretinib and DP-5439 are substrates for P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP). Ripretinib is an inhibitor of P-gp and BCRP. DP-5439 is an inhibitor of BCRP and Multidrug And Toxin Extrusion Protein 1 (MATE1).

Carcinogenicity studies have not been conducted with ripretinib. Ripretinib was not mutagenic in an in vitro bacterial reverse mutation (Ames) assay or clastogenic in either an in vitro human lymphocyte culture micronucleus assay or an in vivo rat bone marrow micronucleus assay. Dedicated fertility studies in male animals were not conducted with ripretinib. Findings in male reproductive organs occurred in repeat-dose toxicity studies and included degeneration of the testes and cellular debris of the epididymis in males administered ≥30 mg/kg/day (approximately one half of the human exposure at the recommended dose of 150 mg).

The efficacy of QINLOCK was evaluated in INVICTUS, an international, multi-center, randomized (2:1), double-blind, placebo-controlled trial (NCT03353753). Eligible patients had unresectable, locally advanced or metastatic gastrointestinal stromal tumor (GIST) and had received prior treatment with imatinib, sunitinib, and regorafenib. Randomization was stratified by prior lines of therapy (3 versus ≥4) and Eastern Cooperative Oncology Group (ECOG) performance status (0 versus 1 or 2). Patients received QINLOCK 150 mg or placebo orally once daily until disease progression or unacceptable toxicity. Tumor response assessments were performed every 28 days through for the first 4 months and then every 56 days thereafter. The major efficacy outcome measure was progression-free survival (PFS) based on disease assessment by blinded independent central review (BICR) using modified RECIST 1.1 criteria, in which lymph nodes and bone lesions were not target lesions and a progressively growing new tumor nodule within a pre-existing tumor mass must meet specific criteria to be considered unequivocal evidence of progression. Additional efficacy outcome measures included objective response rate (ORR) by BICR and overall survival (OS). Patients randomized to receive placebo could be treated with QINLOCK at the time of disease progression. A total of 129 patients were randomized, 85 to QINLOCK and 44 to placebo. Patient characteristics of the intent-to-treat (ITT) population in INVICTUS were median age of 60 years (range: 29 to 83 years), with 39% aged ≥65 years; 57% were male; 75% were White; and 92% had an ECOG performance status of 0 or 1. Sixty-three percent (63%) of patients received 3 prior therapies and 37% received 4 or more prior therapies. Sixty-six percent (66%) of patients randomized to placebo switched to QINLOCK after disease progression. Efficacy results from INVICTUS are summarized in Table 6 . Table 6: Efficacy Results of INVICTUS BICR=Blinded Independent Central Review; CI=Confidence Interval a. Assessed per BICR. b. p-value is based on 2-sided stratified log-rank test. c. Hazard ratio is based on Cox proportional regression model. This model includes treatment and randomization stratification factors as fixed factors. d. Based on Fisher's exact test. The p-value is not statistically significant. e. Not evaluated for statistical significance as a result of the sequential testing procedure for the secondary endpoints of ORR and OS. QINLOCK (N=85) Placebo (N=44) Progression-Free Survival a Number of events (%) 51 (60) 37 (84)      Progressive disease 46 (54) 32 (73)      Deaths 5 (6) 5 (11) Median PFS (months) (95% CI) 6.3 (4.6, 6.9) 1.0 (0.9, 1.7) Hazard ratio (95% CI) c 0.15 (0.09, 0.25) p-value b < 0.0001 Overall Response Rate a Overall Response Rate (%) 9 0 (95% CI) (4.2, 18) (0, 8) p-value d 0.0504 Overall Survival e Number of deaths (%) 26 (31) 26 (59) Median OS (months) (95% CI) 15.1 (12.3, 15.1) 6.6 (4.1, 11.6) Hazard ratio (95% CI) c 0.36 (0.21, 0.62) Figure 1: Kaplan-Meier Curve of Progression-Free Survival in INVICTUS Figure 2: Kaplan-Meier Curve of Overall Survival in INVICTUS Figure 1 Figure 2

This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: 10/2023 Patient Information QINLOCK ® (kin-lok) (ripretinib) tablets What is QINLOCK? QINLOCK is a prescription medicine used to treat adults with advanced gastrointestinal stromal tumor (GIST) who have received prior treatment with 3 or more kinase inhibitor medicines, including imatinib, for their GIST. It is not known if QINLOCK is safe and effective in children. Before taking QINLOCK, tell your healthcare provider about all of your medical conditions, including if you: had a type of skin problem called palmar-plantar erythrodysesthesia syndrome have high blood pressure have heart problems had or plan to have surgery are pregnant or plan to become pregnant. QINLOCK can harm your unborn baby. Tell your healthcare provider if you or your partner becomes pregnant or you think you may be pregnant during treatment with QINLOCK. Females who are able to become pregnant: Your healthcare provider will do a pregnancy test before you start treatment with QINLOCK. You should use effective birth control (contraception) during treatment with QINLOCK and for 1 week after the last dose. Talk to your healthcare provider about birth control methods that may be right for you. Males with female partners who are able to become pregnant: You should use effective birth control during treatment with QINLOCK and for at least 1 week after your final dose. are breastfeeding or plan to breastfeed. It is not known if QINLOCK passes into your breast milk. Do not breastfeed during treatment with QINLOCK and for at least 1 week after your final dose. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. QINLOCK and certain other medicines can affect each other causing side effects or affect how QINLOCK works. Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine. What should I avoid while taking QINLOCK? Your skin may be sensitive to the sun or other forms of light (photosensitivity) during treatment with QINLOCK. Avoid or limit exposure to direct sunlight, sunlamps, and other sources of ultraviolet radiation during treatment and for at least 1 week after stopping treatment with QINLOCK. Use sunscreen and wear clothes that cover your skin if you need to be out in the sun. How should I take QINLOCK? Take QINLOCK exactly as your healthcare provider tells you to. Your healthcare provider may temporarily or permanently stop treatment or change your dose of QINLOCK if you develop side effects during treatment. Do not change your dose or stop taking QINLOCK unless your healthcare provider tells you to. Take QINLOCK 1 time each day, at the same time each day. Take QINLOCK with or without food. Swallow QINLOCK tablets whole. If you vomit after taking a dose of QINLOCK, do not take an extra dose. Take your next dose of QINLOCK at your scheduled time. If you miss a dose of QINLOCK, take it as soon as you remember if it is within 8 hours of the scheduled dose. If more than 8 hours have passed, wait until your next scheduled dose. If you take more than the prescribed dose of QINLOCK, call your healthcare provider. What are the possible side effects of QINLOCK? QINLOCK may cause serious side effects, including: A skin problem called palmar-plantar erythrodysesthesia syndrome. Skin problems are common and sometimes can be severe. Tell your healthcare provider right away if you develop redness, pain, blisters, bleeding, or swelling on the palms of your hands or soles of your feet, or severe rash during treatment with QINLOCK. New skin cancers. QINLOCK may cause skin cancers called cutaneous squamous cell carcinoma, keratoacanthoma, or melanoma. Talk to your healthcare provider about your risk for these cancers. Your healthcare provider should check your skin before and during treatment with QINLOCK to look for any new skin cancers. Check your skin and tell your healthcare provider right away about any skin changes, including a: new wart skin sore or reddish bump that bleeds or does not heal change in size or color of a mole High blood pressure (Hypertension). High blood pressure is common with QINLOCK and can be severe. Your healthcare provider should check your blood pressure regularly during treatment with QINLOCK. Heart problems. Your healthcare provider should check you for signs or symptoms of heart failure before starting QINLOCK and regularly during treatment with QINLOCK. Heart failure can be serious and can sometimes lead to death. Tell your healthcare provider right away if you have any of the following signs or symptoms during your treatment with QINLOCK: tiredness swelling of your stomach-area (abdomen), legs or ankles shortness of breath protruding neck veins Risk of wound healing problems. Wounds may not heal well during treatment with QINLOCK. Tell your healthcare provider if you plan to have any surgery before or during treatment with QINLOCK. Your healthcare provider should tell you when to stop taking QINLOCK before a planned surgery. Your healthcare provider should tell you when you may start taking QINLOCK again after surgery. Risk of sensitivity to sunlight (photosensitivity). See “What should I avoid while taking QINLOCK?” The most common side effects of QINLOCK include: hair thinning or hair loss nausea constipation diarrhea vomiting tiredness stomach (abdominal) pain muscle pain decreased appetite QINLOCK may affect fertility in males which may affect the ability to have children. Talk to your healthcare provider if this is a concern for you. These are not all the possible side effects of QINLOCK. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store QINLOCK? Store QINLOCK in the original container at room temperature between 68ºF to 77ºF (20ºC to 25ºC). QINLOCK comes with a desiccant packet in the bottle to protect your medicine from moisture. Do not remove the desiccant packet from the bottle. Keep QINLOCK and all medicines out of the reach of children. General information about the safe and effective use of QINLOCK. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use QINLOCK for a condition for which it was not prescribed. Do not give QINLOCK to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about QINLOCK that is written for health professionals. What are the ingredients in QINLOCK? Active ingredient: ripretinib Inactive ingredients: crospovidone, hypromellose acetate succinate, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and silicon dioxide Manufactured for: Deciphera Pharmaceuticals, LLC , 200 Smith Street, Waltham, MA 02451 QINLOCK is a trademark of Deciphera, LLC. All other trademarks referenced herein are the property of their respective owners. For more information, call 1-888-724-3274 or go to www.QINLOCK.com

Principal Display Panel - 90 Tablet Carton Label NDC: 73207-101-30 Rx only QINLOCK™ (ripretinib) tablets 50 mg Dispense the enclosed Patient Information Leaflet to each patient. 90 TABLETS Principal Display Panel - 90 Tablet Carton Label