QINLOCK

What it is

QINLOCK contains 50 mg of ripretinib per tablet. Ripretinib is a switch-control tyrosine kinase inhibitor with a dual mechanism of action that binds to both the switch pocket and the activation loop to lock the kinase in the inactive state, preventing downstream signalling and cell proliferation. This dual mechanism of action provides broad inhibition of KIT and PDGFRA kinase activity, including wild type and multiple primary and secondary mutations.

Approved indications

— Advanced gastrointestinal stromal tumours (GIST) in adult patients who have received prior treatment with 3 or more kinase inhibitors, including imatinib.

Dosing overview

The recommended dosage of QINLOCK is 150 mg (three 50 mg tablets) orally once daily with or without food until disease progression or unacceptable toxicity. The recommended dose reduction for adverse reactions is QINLOCK 100 mg orally once daily.

Key safety warnings

**Palmar-plantar erythrodysaesthesia syndrome.** Grade 1–2 palmar-plantar erythrodysaesthesia syndrome occurred in 21% of patients who received QINLOCK in the INVICTUS trial. Based on severity, QINLOCK should be withheld and then resumed at same or reduced dose. **New primary cutaneous malignancies.** Cutaneous squamous cell carcinoma occurred in 4.7% of patients who received QINLOCK, with a median time to event of 4.6 months. Melanoma occurred in 2.4% of patients who received QINLOCK. Perform dermatologic evaluations when initiating QINLOCK and routinely during treatment, and manage suspicious skin lesions with excision and dermatopathologic evaluation. **Hypertension.** Grade 1–3 hypertension occurred in 14% of patients who received QINLOCK, including Grade 3 hypertension in 7%. Do not initiate QINLOCK in patients with uncontrolled hypertension, and adequately control blood pressure prior to initiating QINLOCK. **Cardiac dysfunction.** Cardiac failure occurred in 1.2% of patients in the INVICTUS trial and 1.7% in the pooled safety population, including Grade 3 adverse reactions in 1.1%. The safety of QINLOCK has not been assessed in patients with a baseline ejection fraction below 50%, and ejection fraction should be assessed 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. **Wound healing.** Impaired wound healing complications can occur in patients who receive drugs that inhibit the vascular endothelial growth factor signaling pathway, and QINLOCK has the potential to adversely affect wound healing. Withhold QINLOCK for at least 1 week prior to elective surgery and do not administer for at least 2 weeks following major surgery and until adequate wound healing. **Phototoxicity.** Due to the risk of phototoxicity, it is recommended to advise patients to avoid or minimise exposure to direct sunlight, sunlamps, and other sources of ultraviolet radiation during treatment with QINLOCK and for at least one week after discontinuation, and patients should use protective clothing and sunscreen with high sun protection factor.

Contraindications

Use of QINLOCK is contraindicated in patients with hypersensitivity to ripretinib or to any other component of QINLOCK tablets.

PBS listing

QINLOCK 50 mg tablets are listed on the PBS as 1 item with authority required restriction, at an ex-manufacturer price of A$16141.94.

Regulatory history

The TGA approved QINLOCK on 10 July 2020 for the treatment of adult patients with advanced gastrointestinal stromal tumours (GIST) who have received prior treatment with 3 or more kinase inhibitors, including imatinib. The PBAC initially did not recommend QINLOCK in March 2021 but recommended it in July 2021 for gastrointestinal stromal tumour.