dm+d

Unassigned

New Medicines

QinlockAdvanced gastrointestinal stromal tumours (GIST) - fourth-line

Information

Qinlock
New molecular entity
Deciphera
Deciphera

Development and Regulatory status

Approved (Licensed)
Approved (Licensed)
Launched
Yes
Dec 21MHRA add Qinlock to orphan register indicating its license is granted [17].
Dec 21Following failure of the INTRIGUE study, Deciphera Pharmaceuticals announced they are streamlining commercial activities related to ripretinib (Qinlock), focusing on commercialisation for 4th-line GIST in the USA. It will reduce its USA-based commercial team, while maintaining limited direct commercial presence in Europe to support launch in Germany and France. It plans to provide access in other European countries via other channels. Further clinical development of ripretinib will be discontinued [15,16]
Dec 21Qinlock 50mg tablets approved in UK. Indication is for adults with GIST that has - spread to other parts of the body or cannot be removed by surgery - been treated with at least 3 previous cancer medicines, including imatinib [17].
Nov 21Approved in EU [14].
Sep 21Recommended for EU approval by CHMP – “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.” Qinlock will be available as 50mg tablets [12].
Oct 20Filed in EU via centralised procedure [11].
May 20Ripretinib will be launched this week, priced at $32,000 per month, in the US [10].
May 20Approved in US [8].
Feb 20FDA has awarded a Priority Review, which means time to potential approval will be shortened. It is anticipated that it will be marketed in the US by the end of 2020 [7].
Jan 20According to its latest quarterly report, Deciphera is building its own focused, specialised sales and marketing organisation in the US. Outside of the US, in addition to our existing ripretinib license to Zai for Greater China, it plans to selectively establish partnerships in markets outside the US to support commercialisation of drug candidates, and is currently exploring the possibility of building its own sales capabilities in Europe as an alternative to partnering [6].
Dec 19Filed in US.[4]
Dec 19Granted Breakthrough Therapy Status in US.[4]

Category

KIT/PDGFRα-targeted kinase inhibitor
Gastrointestinal stromal tumours (GISTs) are rare, representing about 0.1 to 3% of gastrointestinal tumours [1].
Advanced gastrointestinal stromal tumours (GIST) - fourth-line
Oral

Further information

Yes

Trial or other data

Jan 22Results from the PIII INTRIGUE study of ripretinib (Qinlock) in patients with gastrointestinal stromal tumor (GIST) previously treated with imatinib presented at the American Society of Clinical Oncology (ASCO) Plenary Series Session. Although the INTRIGUE study did not meet its primary endpoint of superiority in progression-free survival vs sunitinib, the efficacy of ripretinib appears comparable to sunitinib in 2nd line patients. In addition, ripretinib had a more favourable safety profile than sunitinib with fewer Grade 3/4 adverse events and patients reported less deterioration in role functioning and several other key patient-reported outcome measures of tolerability [18].
Nov 21PIII INTRIGUE study (n=453) fails to meet primary outcome of improved PFS vs. SOC with sunitinib (8.0 months vs 8.3 months, respectively; HR 1.05, p=0.715) [13].
Jun 20PIII INVICTUS study NCT03353753 is published; ripretinib significantly improved median progression-free survival vs placebo with an acceptable safety profile in 129 patients with treatment resistant disease (6.3 vs 1.0 months; HR 0.15, 95% CI 0.09–0.25; p<0.0001) [9].
Jun 20PIII INVICTUS study NCT03353753 is published; ripretinib significantly improved median progression-free survival vs placebo with an acceptable safety profile in 129 patients with treatment resistant disease (6.3 vs 1.0 months; HR 0.15, 95% CI 0.09–0.25; p<0.0001) [9].
Nov 19PIII Intrigue study (NCT03673501) is still recruiting [5].
Nov 19Deciphera Pharmceuticals initiates an expanded access program for ripretinib in patients with locally advanced unresectable or metastatic GIST and have received treatment with at least 2 prior approved therapies (NCT04148092). Under the EAP, ripertinib will be available for treatment until discontinuation of the programme or commercially launch of the drug in the US and outside of the US (countries not stated) [5].
Feb 19PIII study (NCT03353753) loking at DCC-2618 versus placebo in the treatment of advanced GIST patients who have received prior anticancer treatment is active but not recruiting. This is a 2 arm, randomised, double-blind, cross-over study. Prior treatments must include imatinib, sunitinib, and regorafenib. The primary outcome is progression free survival at 15 months [2].
Feb 19PIII study (NCT03673501) is an open-label, randomised, multi-centre study comparing efficacy of DCC-2618 to sunitinib in patients who progressed on or were intolerant to first-line treatment with imatinib. The study aims to recruit 358 patients. The study commenced on 11/2/19 and aims for a primary completion date of June 2021 [2].
Feb 19The company has reported three-month data indicating ripretinib achieved disease control rates of 81% as second- and third-line GIST therapy, and 66% in fourth-line patients. Overall response rates were 21% and 9%, respectively. Median progression-free survival was 42 weeks for 2nd-line, 40 weeks for 3rd-line, and 24 weeks for 4th-line [3].

Evidence based evaluations