Drug Detail

Information about QINLOCK

Generic Name
Ripretinib
IND
DCC-2618
Brand Name (US)
QINLOCK
Manufacturer
Deciphera Pharmaceuticals, LLC
Drug Type
Tyrosine Kinase Inhibitor
Delivery
Oral
Approval Status
Approved for GIST
Indications
4th line GIST
Overall Strategy
KIT Protein Based
Strategy
Block KIT
Drug Category
KIT/PDGFRA inhibitor

On May 15th, 2020, ripretiinib was approved for GIST patients with three or more previous treatments.
DCC-2618 is a new kind of tyrosine kinase inhibitor (TKI). Traditional TKI's work by blocking access of ATP. Deciphera's technology binds to TKI's in a different region of the protein, the "switch pocket". Pre-clinical evidence suggests that these drugs, including DCC-2618, are able to block signaling of a wide range of secondary mutations that cause resistance to Gleevec and other TKI's.
• inhibitor of primary mutant cKIT kinase

• inhibitor of secondary mutations, including exons 14 and 17.

• inhibitor of PDGFR-alpha and KDR kinases

DCC-2618 inhibits the primary mutant form of cKIT kinase ( D JMD-KIT) causative of gastrointestinal stromal tumors (GIST) in 90% of newly diagnosed patients. Importantly, it also inhibits major secondary mutant forms of D JMD-KIT, wherein patients present with additional mutations: V654A, D816V, D816H, or the gatekeeper mutant T670I. Greater than 50% of patients on therapy for GIST develop resistance to currently marketed drugs due to the emergence of these secondary mutations. It was being developed to provide patients with superior coverage of all of the mutant forms of cKIT responsible for both primary and refractory GIST. DCC-2618 has demonstrated potent in vivo inhibition of KIT in animal models.


Links

 

Access to QINLOCK (Decipheraaccesspoint.com)
   

 

QINLOCK website (Deciphera). Manufacturers website
   

 

Ripretinib prescribing information
   

 

Translational Data Presented at the 2017 American Association for Cancer Research (AACR) Annual Meeting
   

 

12/1/2016 EEORTC-NIH-AACR meeting abstract
   

 

Deciphera pipeline description of DCC-2618
   

 

Dermatopathological review of cutaneous squamous cell carcinoma events in patients with GIST treated with ripretinib
   

 

Deciphersa Switch Pocket Type II Inhibitors graphics
   

 

6/1/2010 ASCO - In vitro activity of novel KIT/PDGFRA switch pocket kinase inhibitors against mutations associated with drug-resistant GI stromal tumors.
   

 

4/1/2009 AACR #3733- Small molecule modulators of KIT kinase for treatment of gastrointestinal stromal tumors (GIST). Inhibitors of juxtamembrane domain, D816V, T670I and V654A mutant forms
   

Trials of this drug

  

A Safety, Tolerability and PK Study of DCC-2618 in Patients With Advanced Malignancies
   

  

Phase 3 Study of DCC-2618 vs Placebo in Advanced GIST Patients Who Have Been Treated With Prior Anticancer Therapies (invictus)
   

  

A Study of DCC-2618 vs Sunitinib in Advanced GIST Patients After Treatment With Imatinib (intrigue)
   

Trial results

  Switch Control Inhibition of KIT and PDGFRA in Patients With Advanced Gastrointestinal Stromal Tumor: A Phase I Study of Ripretinib
   
  Repretinib in patients with advanced GIST (INVICTUS): a double-placebo, randomised, placebo-controlled, phase 3 trial
   

Search for this drug/combination in:

ClinicalTrials.gov

ASCO

Pubmed