Study: Ripretinib BID Well-Tolerated With Similar Safety Profile to Ripretinib QD in GIST

The results of the randomized, double-blind, placebo-controlled, international, multicenter INVICTUS phase 3 study evaluating the safety, tolerability, and efficacy of ripretinib (Qinlock; Deciphera Pharmaceuticals) compared to placebo in patients with advanced gastrointestinal stromal tumor (GIST) were presented during a session at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. The study specifically looked at patients with GIST whose previous therapies have included at least imatinib, sunitinib, and regorafenib.

Primary results from the randomized portion of the INVICTUS study had previously shown that ripretinib was able to significantly improve progression-free survival (PFS) with a clinically meaningful overall survival (OS) benefit. Additionally, the investigators conducted an exploratory analysis to assess the safety and efficacy of a dose escalation for ripretinib to 150 mg twice a day (BID) among patients randomized to the ripretinib arm in the study.

The study had a cutoff date set at August 10, 2020; at this point, 43 of 85 randomized patients were dose escalated to 150 mg BID after disease progression by blinded independent central review using a modified RECIST version 1.1.

Among these 43 dose-escalated patients, initial median PFS (mPFS1) was 4.6 months (95% CI 2.7–6.4), whereas the subsequent median PFS (mPFS2) from the day of dose escalation to second disease progression or death was 3.7 months (95% CI 3.1–5.3). Upon assessment, the ratio of mPFS2/mPFS1 was found to be 80%.

In patients with progressive disease who were dose escalated to 150 mg BID (n=43), the median OS was 18.4 months. Among those with progressive disease who were not dose escalated (n=22), the median OS was found to be 14.2 months (HR 0.74, 95% CI 0.37–1.49).

Overall, the investigators observed that ripretinib at 150 mg BID was found to be well-tolerated with a similar safety profile to ripretinib at 150 mg once a day (QD). Additionally, they observed new or worsening grade 3 to 4 treatment-emergent adverse events of anemia in 6 patients (14%) and abdominal pain in 3 patients (7%).

“The data presented at ASCO further demonstrate the important clinical benefits QINLOCK can provide in this population,” said Matthew L. Sherman, MD, executive vice president and chief medical officer of Deciphera, in a press release. “Importantly, consistent with our phase 1 data, these exploratory results from the phase 3 study show that dose escalation to QINLOCK 150 mg BID after disease progression on QINLOCK 150 mg QD can offer substantial additional clinical benefit with a tolerable safety profile. As the body of data supporting QINLOCK’s efficacy and safety continues to grow, we are pleased with QINLOCK’s potential to offer clinically meaningful benefit for GIST patients in multiple settings of the disease.”

REFERENCE

Deciphera Pharmaceuticals Presents Data from QINLOCK® and Rebastinib Programs at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Waltham, MA: Deciphera Pharmaceuticals; June 4, 2021. https://www.businesswire.com/news/home/20210604005122/en/Deciphera-Pharmaceuticals-Presents-Data-from-QINLOCK%C2%AE-and-Rebastinib-Programs-at-the-2021-American-Society-of-Clinical-Oncology-ASCO-Annual-Meeting. Accessed June 21, 2021.