...CStone Pharmaceuticals...a leading biopharmaceutical company focused on developing and commercializing innovative immuno-oncology therapies and precision medicines, today announces that the National Medical Products Administration (NMPA) of China has approved AYVAKIT (avapritinib) tablets for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations.

Blueprint Medicines Corporation (NASDAQ: BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, today announced that the European Commission (EC) has granted conditional marketing authorization to AYVAKYT® (avapritinib) as a monotherapy for the treatment of adult patients with unresectable or metastatic gastrointestinal stromal tumors (GIST) harboring the platelet-derived growth factor receptor alpha (PDGFRA) D842V mutation.

Ayvakyt is indicated as monotherapy for the treatment of adult patients with unresectable or metastatic gastrointestinal stromal tumours (GIST) harbouring the platelet-derived growth factor receptor alpha (PDGFRA) D842V mutation.

AYVAKIT is a kinase inhibitor indicated 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.

Gastrointestinal Stromal Tumors: First-line therapy…Preferred Regimens…Avapritinib (for GIST with PDGFRA exon 18 mutations, including the PDGFRA D842V mutation)...

...Group 1: Patients must have a confirmed diagnosis of unresectable GIST that has progressed following imatinib and at least 1 of the following: sunitinib, regorafenib, sorafenib, dasatinib, pazopanib, or an experimental kinase-inhibitor agent, and the patient does not have a D842V mutation in PDGFRα...

In patients with PDGFRA D842V mutations, IRRC- and investigator-assessed ORRs were 75% and 79%, respectively; clinical benefit rates were both 86%. Median duration of response/progression-free survival were not reached. IRCC- and investigator-assessed ORRs in patients in the fourth- or later-line setting were 22% and 35%, respectively. Median progression-free survivals were 5.6 months for both....Avapritinib was generally well tolerated and showed marked anti-tumor activity in Chinese patients with GIST bearing PDGFRA D842V mutations and notable efficacy as fourth- or later-line monotherapy.

As assessed by investigators, of the 20 pts with D842V-mutant, 15 pts had PR leading to a 75% ORR; of the 23 pts with 4L+ GIST, 9 (39%) pts had an objective response, with 1 (4%) CR and 8 (35%) PRs. Most responders (D842V-mutant [13] and 4L+ GIST [7]) remain in remission. Our data show that avapritinib demonstrated strong antitumor activity in pts with PDGFRA D842V-mutant and 4L+ GIST, making it an important potential new treatment option for the population.

Fifty-six (NAVIGATOR) and 19 (Study 1002) patients with PDGFRA D842V-mutant GIST were evaluated; of the 56 patients from NAVIGATOR, a subgroup of patients treated with either 300 mg (recommended phase 2 dose) or 400 mg (maximum tolerated dose) avapritinib starting dose (n = 38) were analyzed separately...Adjusted median PFS was 29.5 months in NAVIGATOR...

...patients (pts) with unresectable or metastatic (U/M) PDGFRA D842V-mutant gastrointestinal stromal tumour (GIST) treated with avapritinib…an overall response rate (ORR, modified Response Evaluation Criteria in Solid Tumors version 1.1) of 95%, with 5 (13%) complete responses (CR), and 31 (82%) partial responses (PR)...Median progression-free survival (PFS) was 24 mo (95% CI 18–NR), and median overall survival (OS) was NR; PFS and OS rates at 36 mo were 34% and 71%, respectively.

In pts with U/M PDGFRA D842V-mutant GIST, avapritinib has clinical activity with durable responses and a tolerable safety profile, with no additional safety signals to those found in the NAVIGATOR study overall GIST population.

OS rate at 6 and 24 mo was 100% and 75% in NAVIGATOR vs 84% and 63% in Study 1002 (K–M curve comparison: P=0.0085)....OS rate at 6 and 24 mo was 100% and 77% in NAVIGATOR vs 56% and 38% in Study 1002, respectively (K–M curve comparison: P=0.0001)....Unadjusted/adjusted PFS rates at 6 and 24 mo were 92%/93% and 77%/71% in NAVIGATOR vs 14%/9% and 7%/6% in Study 1002 (K–M curve comparison: P=0.0000)....AVA demonstrated significantly more durable survival outcomes compared with other TKIs used to treat pts with U/M PDGFRA D842V-mutant GIST.

...38 patients with PDGFRA D842V-mutant GIST treated at 300/400 mg achieved an overall response rate (ORR, modified Response Evaluation Criteria in Solid Tumours version 1.1) of 95%, with 5 (13%) complete responses (CR) and 31 (82%) partial responses (PR); of the 5 tyrosine kinase inhibitor-naïve patients, 2 had a CR and 3 a PR.

...Blueprint Medicines , announced on July 24th that the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion, recommending conditional marketing authorization for avapritinib as a monotherapy for the treatment of adult patients with unresectable or metastatic gastrointestinal stromal tumors (GIST) harboring the PDGFRA D842V mutation.

Avapritinib has a manageable safety profile and has preliminary antitumour activity in patients with advanced PDGFRA D842V-mutant gastrointestinal stromal tumours.

Results from the Phase I trial of avapritinib have indicated that this drug should be the standard of care for patients with PDGFRA exon 18 D842V-mutated GIST.

Between 7 October 2015 and 9 March 2020, 250 patients enrolled in the safety population; 56 patients were included in the PDGFRA D842V population...The median DOR was 27.6 months (95% confidence interval [CI]: 17.6-not reached [NR]); median PFS was 34.0 months (95% CI: 22.9-NR).

Adult pts with unresectable PDGFRA D842V or other mutant GIST who progressed on imatinib and ≥ 1 other tyrosine kinase inhibitor (TKI) were treated with oral, daily, continuous avapritinib...The Ex 18 ORR was 86% [3 CR, 34 PR (1 pending)] and 5 SD; mDOR was not reached (95% CI: 11.3-NE).

A 76-year-old gentleman presented with gastric GIST...Mutation testing was suggestive of PDGFRA D842V mutation. He was started on avapritinib and response assessment at 3 months was suggestive of a partial response (Figure 5).