What is QINLOCK used for?

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

What pharmaceutical form is QINLOCK available in?

QINLOCK: Tabletki 50 mg (doustna)

What are the side effects of QINLOCK?

Summary of the safety profile In the Phase 3 double-blind, randomised (2:1), placebo-controlled study (INVICTUS), 129 participants with a diagnosis of advanced GIST who had failed at least 3 approved prior lines of treatment were randomised to QINLOCK (n=85) or placebo (n=44) (see section5.1). In the Phase 1 Study DCC-2618-01-001, a total of 277 patients with advanced malignancies were enrolled, and 218 patients were treated at the recommended Phase 2 dose of 150 mg QINLOCK onc

Who should NOT take QINLOCK?

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Does QINLOCK interact with other medications?

Both ripretinib and its active metabolite DP-5439 are mainly cleared by CYP3A4/5 and are substrates of P-gp and Breast Cancer Resistance Protein (BCRP). Effect of other medicinal products on ripretinib Effect of strong CYP3A/P-gp inhibitors Co-administration of itraconazole (a strong CYP3A inhibitor) and also a P-gp inhibitor increased ripretinib C max by 36% and AUC 0- ∞ by 99%. DP-5439 C max was unchanged; AUC 0- ∞ increased by 99%. Strong inhibitors of CYP3A/P-gp (e.g. ketoc

Can QINLOCK be used during pregnancy?

Women of childbearing potential/Contraception in males and females Women of childbearing potential and men with female partners of reproductive potential must be informed that QINLOCK may cause foetal harm and must ensure effective contraception during treatment and for at least 1 week after the final dose of QINLOCK (see section 4.4) The pregnancy status of females of reproductive potential is to be verified prior to initiating QINLOCK and during treatment. Effects of QINLOCK on contraceptive s

What precautions should be taken with QINLOCK?

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Who manufactures QINLOCK?

Deciphera Pharmaceuticals (Netherlands) B.V. (Holandia)

What ATC class does QINLOCK belong to?

QINLOCK: ATC L01EX19. ATC is the WHO Anatomical Therapeutic Chemical classification — it groups drugs by organ system and pharmacological mechanism.

QINLOCK

This information is for educational purposes only. It is not intended as medical advice. Always consult a qualified healthcare professional.

Pharmacotherapeutic group: Antineoplastic agents, other protein kinase inhibitors; ATC Code: L01EX19 Mechanism of action Ripretinib is a novel tyrosine kinase inhibitor that inhibits KIT proto-oncogene receptor tyrosine kinase and PDGFRA kinase, including wild type, primary, and secondary mutations.‍‍‍‍‍‍‍‍‍‍‍‍‍ Ripretinib also inhibits other kinases in vitro , such as PDGFRB, TIE2, VEGFR2, and BRAF. Clinical efficacy and safety INVICTUS (DCC-2618-03-001 study) The efficacy and safety of QINLOCK were evaluated in a randomised (2:1), double-blind, placebo-controlled study (INVICTUS study) in patients with unresectable, locally advanced or metastatic GIST who had been previously treated with or are intolerant to at least 3 prior anticancer therapies including treatment with imatinib, sunitinib, and regorafenib. Randomisation was stratified by prior lines of therapy (3 versus ≥4) and Eastern Cooperative Oncology Group (ECOG) performance status (0 versus 1 or 2). The primary 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 tumour nodule within a pre-existing tumour mass must meet specific criteria to be considered unequivocal evidence of progression. Secondary efficacy endpoints included objective response rate (ORR) by BICR, overall survival (OS), and patient- reported health state, physical function (PF), and role function (RF). Participants were randomised to receive 150 mg QINLOCK (n=85) or placebo (n=44) orally once daily administered in continuous 28-day cycles. Treatment continued until disease progression or unacceptable toxicity. Individual treatment arms were unblinded at the time of disease progression as assessed by BICR review and all patients on placebo arm were offered to cross-over to QINLOCK. The demographic characteristics were median age of 60 years (29 to 83 years) with 79 (61.2%) of patients aged 18-64 years, 32 (24.8%) of patients aged 65- 74 years, and 18 (13.9%) patients aged ≥ 75 years (no patients ≥ 85 years old were randomised); male (56.6%); white (75.2%); and ECOG performance status of 0 (41.9%), 1 (49.6%), or 2 (8.5%). Sixty-three percent (63%) of patients received 3 prior therapies and approximately 37% received 4 or more prior therapies. Sixty-six percent (66%) of patients randomised to placebo crossed over to QINLOCK during the open-label period. At the primary analysis (data cut-off date 31 May 2019) QINLOCK was compared to placebo in the INVICTUS study. QINLOCK demonstrated benefit in all assessed patient subgroups for PFS. Median PFS as determined by BICR (months) (95% CI) was 6.3 (4.6, 6.9) for QINLOCK versus 1.0 (0.9, 1.7) for placebo, HR (95% CI) 0.15 (0.09, 0.25) p-value < 0.0001. The secondary endpoint ORR (%) was 9.4 (4.2, 18) for QINLOCK versus 0 (0, 8) for placebo, p-value 0.0504 and not statistically significant. Median OS (months) (95% CI) was 15.1 (12.3, 15.1) for QINLOCK versus 6.6 (4.1, 11.6) for placebo, nominal p-value 0.0004. OS was not evaluated for statistical significance as a result of the sequential testing procedure for the secondary endpoints of ORR and OS. PFS, ORR and OS results from a more recent data cut-off (10 August 2020) are shown in Table 3 and Figures 1 and 2. PFS results were similar across subgroups based on age, sex, region, ECOG status and number of previous lines of therapy. Table 3: INVICTUS efficacy results (as of 10 August 2020) QINLOCK (n = 85) Placebo (n = 44) PFS a Number of events (%) 68 (80) 37 (84) Progressive disease 62 (73) 32 (73) Deaths 6 (7) 5 (11) Median PFS (months) (95% CI) 6.3 (4.6, 8.1) 1.0 (0.9, 1.7) HR (95% CI) b 0.16 (0.10, 0.27) ORR a ORR (%) 11.8 0 (95% CI) (5.8, 20.6) (0, 8) OS Number of deaths (%) 44 (52) 35 (80) Median OS (months) (95% CI) 18.2 (13.1, NE) 6.3 (4.1, 10.0) HR (95% CI) b 0.42 (0.27, 0.67) BICR = Blinded Independent Central Review; CI = Confidence Interval; HR = Hazard Ratio; ORR = Objective Response Rate; NE = not estimable; PFS = Progression Free Survival; OS = Overall Survival a Assessed per BICR. b Hazard ratio is based on Cox proportional regression model. This model includes treatment and randomisation stratification factors as fixed factors. Figure 1: INVICTUS Kaplan-Meier curve of progression-free survival a a Data cut off 10 August 2020 Figure 2: INVICTUS Kaplan-Meier curve of overall survival a a Data cut off 10 August 2020 Paediatric population The European Medicines Agency has waived the obligation to submit the results of studies with QINLOCK in all subsets of the paediatric population in the treatment of GIST (see section 4.2 for information on paediatric use).

QINLOCK

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