New Medicines

Ayvakit · Advanced gastrointestinal stromal tumours (GIST)


New molecular entity
Blueprint Medicines Corporation
Blueprint Medicines Corporation

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Approved (Licensed)
Jan 20 · Approved in US for "the treatment of adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations." [7]
Oct 19 · US FDA, following its New drug Application (NDA) mid-cycle review meeting, informs Blueprint Medicines that it intends to split the proposed indications for avapritinib into two separate NDA for PDGFRA Exon 18 mutant GIST regardless of prior therapy and fourth-line GIST. The FDA also requested top-line results from the VOYAGER trial to make a informed review of the proposed fourth-line indication and potential clinical benefit in this population including evaluation of response rate and safety for the fourth-line indication [6].
Aug 19 · Filed in US, with priority review, for the treatment of adult patients with PDGFRa Exon 18 mutant GIST, regardless of prior therapy, and fourth-line GIST, a decision is expected 14/2/20 [5].
Jul 19 · Filed in EU for treatment of adult patients with PDGFRα D842V mutant GIST, regardless of prior therapy, and fourth-line GIST [4].
Jan 19 · Has orphan drug status in EU & US [3].
Jun 17 · Granted breakthrough therapy designation from the US FDA for treatment of patients with unresectable or metastatic PDGFRa D842V-driven GIST. Blueprint Medicines also received feedback from the US FDA in a end-of-PI meeting, stating that, the additional data from the expansion cohort of the PI NAVIGATOR trial in GIST is sufficient to support a New Drug Application of avapritinib which company plans to file for the treatment of PDGFRa D842V-driven GIST [3].


Tyrosine kinase inhibitor designed to selectively inhibit PDGFRa and KIT, targeting their gene mutations including the PDGFRa D842V and KIT exon 17 mutations.
GISTs are rare. They represent 0.1-3% of all gastrointestinal cancers. However GISTs are the most common primary mesenchymal tumours of the gastrointestinal tract. The estimated incidence of GISTs is around 15 per million of population per annum. There are approximately 900 new cases per year in the UK [1].
Advanced gastrointestinal stromal tumours (GIST)

Further information

December 2020

Trial or other data

Mar 18 · Pivotal VOYAGER PIII trial in patients with locally advanced unresectable or metastatic GIST of avapritinib versus regorafenib in patients previously treated with imatinib and one or two other TKIs starts (NCT03465722; BLU285-1303). 460 patients will be recruited in the US, UK, South Korea, European Union, Australia and Asia. The primary efficacy endpoint is progression free survival determined by central radiologic assessment per modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Collection of primary outcome data due to complete Apr 21 [2].
Feb 18 · Enrolment of a third-line or later (KIT-driven) GIST cohort was completed in the PI NAVIGATOR study (NCT02508532), and enrolment of the second-line GIST cohort was initiated. Earlier, Blueprint had announced an expansion of the trial, wherein the recruitment target for patients previously treated with imatinib and at least one additional tyrosine kinase inhibitor (TKI) was increased from 50 to 100 patients, and a new cohort was added, to investigate avapritinib in second-line GIST. The NAVIGATOR trial is designed to investigate the safety and tolerability of multiple ascending doses of avapritinib in patients with unresectable, treatment resistant GIST. The trial intends to evaluate pharmacokinetics, pharmacodynamics, and preliminary antineoplastic activity of avapritinib in patients with GIST whose cancer is driven by PDGFRa D842V and KIT Exon 17 mutants. Approximately 200 patients are expected to enrol into this trial in the US, the UK, the EU and Asia. In November 2017, data from the trial (n=116), demonstrated robust clinical activity and a favourable safety profile of avapritinib. Dosing began at 30mg per day and increased in a stepwise fashion to 400mg per day. Blueprint selected 300mg qid as the recommended part 2 dose (RP2D) for the expansion portion of the clinical trial, with an option to escalate patients to the maximum tolerated dose (MTD) of 400mg qid following two treatment cycles [3].

Evidence based evaluations