GIST

Switch Control Inhibition of KIT and PDGFRA in Patients With Advanced Gastrointestinal Stromal Tumor: A Phase I Study of Ripretinib

In the October 1, 2020 edition of Journal of Clinical Oncology, Filip Janku and colleagues reported on the results of the ripretinib in previously treated advanced GIST.

PURPOSE

Ripretinib , which is a switch control kinase inhibitor, that inhibits a wide range of  KIT and PDGFRA mutations, was assessed in advanced gastrointestinal stromal tumor (GIST). 

PATIENTS AND METHODS

). This was the first-in-human phase I study of ripretinib which included a dose-escalation phase and expansion phase at the recommended phase II dose. Patients included those with advanced GIST, intolerant to or experiencing progression on at least 1 prior line of systemic therapy. Other advanced malignancies were also included. Safety, DLTs, MTD, and preliminary antitumor activity were evaluated.

RESULTS

At data cutoff of August 31, 2019, 258 patients (n = 184 GIST) were enrolled in the study, with 68 patients in the dose-escalation phase. 3 DLTs were reported: grade 3 lipase increase (n = 2; 100 mg and 200 mg twice a day) and grade 4 increased creatine phosphokinase (n = 1; 150 mg once daily). MTD had been reached (max dose evaluated, 200 mg twice a day); 150 mg once daily was established as the recommended face to dose. The most frequent (> 30%) treatment-emergent adverse events in patients with GIST receiving ripretinib 150 mg once daily (n = 142) were:

Alopecia (n = 88 [62.0%]),

Fatigue (n = 78 [54.9%]),

Myalgia (n = 69 [48.6%]),

Nausea (n = 65 [45.8%]),

Palmar-plantar erythrodysesthesia (n = 62 [43.7%]),

Constipation (n = 56 [39.4%]),

Decreased appetite (n = 48 [33.8%]),

Diarrhea (n = 47 [33.1%]).

ORR of 11.3% (n = 16/142) ranging from 7.2% (n = 6/83; 4th line or greater) to 19.4% (n = 6/31; 2nd line) and median PFS ranging from 5.5 months (4th line or greater) to 10.7 months (2nd line), on the basis of investigator assessment, were observed.

The authors concluded “ Ripretinib is a well-tolerated, novel inhibitor of KIT and PDGFRA mutant kinases with promising activity in patients with refractory advanced GIST.”

Reference:

Switch Control Inhibition of KIT and PDGFRA in Patients With Advanced Gastrointestinal Stromal Tumor: A Phase I Study of Ripretinib

https://ascopubs.org/doi/full/10.1200/JCO.20.00522

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