Qinlock(ripretinib)

Qinlock (ripretinib) 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. It received Orphan medicinal product designation on 12 October 2017, and a CHMP positive opinion for marketing authorisation on 16 September 2021. Marketing approvals occurred in May, June, and July 2020, and March and July 2021.

In efficacy studies, ripretinib demonstrated an IC50 of 16 nM for inhibition of KIT wild type, compared to 114 nM for imatinib and 12 nM for sunitinib. For KIT del557-558 (Exon 11), ripretinib showed an IC50 of 0.08 nM, while imatinib had an IC50 of 0.99 nM and sunitinib had an IC50 of 0.67 nM. For KIT V559A (Exon 11), ripretinib's IC50 was 0.09 nM, compared to 2.0 nM for imatinib and 0.59 nM for sunitinib. In mouse studies, the maximum tolerated dose of ripretinib was ≥180 mg/kg twice daily.

Safety data indicated that 17 patients in the ripretinib arm discontinued treatment during the double-blind period, with 4.7% discontinuing due to clinical progression and 3.5% due to death. The probability of any grade myalgia was 27.5% at low exposure and 64.1% at high exposure. The probability of any grade PPES (Palmar-Plantar Erythrodysesthesia Syndrome) was 20.1% at low exposure and 60.9% at high exposure.