In the Chinese population of the global INVICTUS trial, ripretinib was found to have a manageable safety profile and produced a good response rate.
Ripretinib (Qinlock) demonstrated encouraging anti-tumor activity and a manageable safety profile in Chinese patients with advanced, previously-treated gastrointestinal stromal tumors (GIST), according to a presentation given by Jian Li, MD, at the 2021 Connective Tissue Oncology Society Virtual Annual Meeting.
Ripretinib is a switch-control tyrosine kinase inhibitor that regulates both the kinase switch pocket and the activation loop. It was found to broadly inhibit KIT and PDGFRA mutations.
The global phase 3 INVICTUS trial (NCT03353753) enrolled patients with GIST who were on their 4th line or greater of treatment It has an actual enrollment of 129 participants. The primary end point of the trial is progression-free survival (PFS). Secondary end points include objective response rate (ORR), time to tumor progression, overall survival (OS), and quality of life.
The phase 2 bridging study was designed to determine the efficacy of the agent in Chinese patients who progressed after 3 or more prior lines of therapy.
The INVICTUS bridging trial was a single-arm study. During the study, patients received 150 mg daily for 28-day cycles. In order to participate in the study, patients must have document disease progression or intolerance to imatinib, sunitinib (Sutent), and at least one other drug. Additionally, they must have an ECOG score of 0 to 2.
In total, 38 of the 50 patients screened went on to receive 1 or more doses of ripretinib treatment. At the time of data cutoff for the primary analysis, 14 patients were continuing treatment while 10 elected to end treatment. Reasons for ending treatment included adverse events (4), death (2), clinical progression (2), investigator decision (1), and patient request (1).
The median age of the patient population was 55 (range, 37-74) and 69% were male. Fifteen percent of patients received 4 or more lines of therapy and 72% had an ECOG score of 1. Tumor mutations included KIT exon 9 (18%), KIT exon 11 (77%), KIT exon 13/14/17/18 (38%), and KIT wt/PDGFRA wt (5%). Primary tumor sites included gastric (23%), small intestine (72%), colon, rectum, or appendix (3%), and other (3%).
The median PFS was 7.2 months (90% CI, 2.89-7.33), meeting the primary efficacy endpoint. The ORR was 18.4% (95% CI, 7.7-34.3). Eighteen percent of patients had a confirmed partial response and 53% had stable disease at 6 weeks or greater and 34% had stable disease at 12 weeks or greater. The median time to best response was 1.9 months (range, 1-3.8). At the time of primary analysis, the median overall survival was not reached. The 1-year overall survival was 65% (95% CI, 47.38-77.97).
“Thirty patients achieved stable disease lasting at least 12 weeks. So, the disease control rate was 52.6%,” said Li, an oncologist in the Department of Hematology in the Peking Union Medical College Hospital.
In terms of safety, 95% of patients experienced at least 1 treatment-related adverse event (AE). Common AEs included alopecia (44%), bilirubin conjugated increased (26%), anemia (23%), and asthenia (23%). Treatment-related AEs led to a dose interruption in 18% of patients and a dose reduction in 3% of patients. No treatment-related AEs led to death and led to discontinuation in 3% of patients.
“The frequency of treatment related adverse events, leading to ripretinib. but those modification with a generally low. Only 1 patient is continued treatment due to treatment-related adverse event and none lead to death,” said Li.