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Avapritinib demonstrated encouraging clinical activity in Chinese patients with PDGFRA D842V–mutant gastrointestinal stromal in a bridging study of the NAVIGATOR trial.
Avapritinib (Ayvakit) demonstrated encouraging clinical activity in Chinese patients with PDGFRA D842V–mutant gastrointestinal stromal (GIST) in a bridging study of the NAVIGATOR trial (NCT02508532), results of which were presented during the 2021 European Society for Medical Oncology World Congress on Gastrointestinal Cancer.
“Avapritinib had moderate clinical activity in the third and later-line treatment of a Chinese patient with GIST, making it the potential new treatment option for the population,” explained Jian Li, MD, PhD, Beijing Cancer Hospital, Beijing, China, during a presentation of the results.
In the open-label, multicenter phase 1/2 trial designed to evaluate avapritinib in patients with unresectable or metastatic GIST, the median duration of treatment was 25.4 weeks.
In patients with PDGFRA D842V-mutant GIST, the overall response rate (ORR) was 75%, including 15 patients with a partial response (PR). Similarly, in the third- and fourth-line treatment subgroup, 9 (39%) patients had an objective response, with 1 (4%) complete response and 8 (35%) PRs. The researchers noted that most responders (13 and 7, respectively) remain in remission.
The median progression-free survival (PFS) was not reached. In particular, for the PDGFRA D842V-mutant and third- and fourth-line treatment subgroups, median PFS was not reached and 5.5 months, respectively.
Lastly, the researchers noted, avapritinib was rapidly absorbed, and the drug exposure increased proportionally with dose at the steady-state. “The mean T1/2 ranged from 30.9-42.2 hours, supporting once daily dosing,” they wrote.
Grade 3/4 treatment related adverse events (TRAEs) occurred in 41 patients, with the most common being anemia (32%). There were no treatment-related deaths.
Avapritinib – a potent, selective, small-molecule inhibitor that targets KIT/PDGFRA activation loop mutants – was approved in the United States based on findings from the NAVIGATOR study. The agent has been approved in China to treat adult patients with unresectable or metastatic GIST harboring PDGFRA exon 18 mutations, including PDGFRA D842V, as the first approve precision therapy for this patient population in China.
At the meeting, Li reported on updated safety and efficacy data from the CS3007-101/BLU-285-1105, which is a bridging registrational study of the NAVIGATOR trial in China.
In phase 1 of the study, researchers aimed to determine the recommended phase 2 dose – between 200 mg daily (n = 6) and 300 mg (n = 6), and to assess the safety and pharmacokinetic (PK) characteristics (N = 12). In phase 2, they evaluated the preliminary efficacy and further assessed safety and PK (N = 48) following treatment at the 300-mg dose. In addition, the phase 2 study evaluated subgroups of patients: those with PDGFRA D842V-mutant GIST (n = 20) and as a third- or fourth-line treatment in patients who progressed on or could not tolerate standard therapy (n = 28).
Median age was 63 years (range, 43-70). The majority of patients were male (n = 41), had an ECOG performance score of 1 (n = 45), stage IV disease (n = 58), and metastatic disease (n = 59).
As of July 31, 2020, 60 patients were treated with avapritinib, including 6 treated at 200 mg and 54 treated with 300 mg. Forty patients were still on treatment, whereas 10 patients discontinued treatment due to death, 9 from disease progression, and 1 due to AEs.
Li J, Cai S, Deng Y, et al. Updated safety, efficacy, and PK results from an open-label, multicenter, phase I/II study of avapritinib in Chinese patients with unresectable or metastatic gastrointestinal stromal tumors. Ann Oncol. 2021;32(suppl 3). doi:10.1016/j.annonc.2021.05.036