Phase III INVICTUS study results positive for ripretinib in patients with fourth-line and fourth-line plus gastrointestinal stromal tumors

Deciphera Pharmaceuticals, Inc. announced positive top-line data from the INVICTUS pivotal Phase III clinical study of ripretinib, a broad-spectrum KIT and PDGFR alpha inhibitor, in patients with fourth-line and fourth-line plus gastrointestinal stromal tumors (GIST).

“There is a dire unmet need for new therapies that can deliver effective disease control for patients with advanced GIST who have failed currently approved treatment options,” said Margaret von Mehren, MD, Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. “These top-line data from a Phase III, randomized, placebo-controlled study are highly impressive and suggest that ripretinib’s approach of targeting the broad spectrum of KIT and PDGFR alpha mutations known to drive GIST can significantly improve progression free survival in the most heavily pretreated patients. Particularly notable is the magnitude of benefit observed for overall survival in this study.”

The INVICTUS Phase III clinical study is a randomized (2:1), double-blind, placebo-controlled, international, multicenter study to evaluate the safety, tolerability, and efficacy of ripretinib compared to placebo in 129 patients with advanced GIST whose previous therapies have included at least imatinib, sunitinib, and regorafenib. The INVICTUS study achieved its primary endpoint of improved PFS as determined by blinded independent central radiologic review using modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. In the INVICTUS study, ripretinib demonstrated a median PFS of 6.3 months (27.6 weeks) compared to 1.0 month (4.1 weeks) in the placebo arm and significantly reduced the risk of disease progression or death by 85% (HR of 0.15, p<0.0001) compared to placebo. For the key secondary endpoint of objective response rate (ORR), as determined by blinded independent central radiologic review using modified RECIST version 1.1, ripretinib demonstrated an ORR of 9.4% compared with 0% for placebo (p-value=0.0504), which was not statistically significant.

Ripretinib in this study also showed a clinically meaningful improvement over placebo in terms of the secondary endpoint overall survival (OS) (median OS 15.1 months vs. 6.6 months, HR = 0.36, nominal p-value=0.0004). Since statistical significance was not achieved for ORR, the hypothesis testing of OS was not formally performed. According to the pre-specified hierarchical testing procedure of the endpoints, the hypothesis testing of OS cannot be formally conducted unless the test of ORR is statistically significant. The OS data for the placebo arm includes patients taking placebo who, following progression, were crossed-over to ripretinib treatment.

Ripretinib was generally well tolerated and the adverse event results in INVICTUS were consistent with data from previously presented Phase 1 study results. Grade 3 or 4 treatment-emergent adverse events (TEAEs) occurred in 42 (49%) patients on the ripretinib arm compared to 19 (44%) on the placebo arm. Grade 3 or 4 TEAEs greater than 5% of patients in the ripretinib arm were anemia (9%; n=8), abdominal pain (7%; n=6) and hypertension (7%; n=6). Grade 3 or 4 TEAEs greater than 5% of patients in the placebo arm were anemia (14%; n=6).

Based on the positive INVICTUS data, the Company expects to submit a New Drug Application (NDA) to the FDA for ripretinib for the treatment of patients with advanced GIST who have received prior treatment with imatinib, sunitinib and regorafenib in the first quarter of 2020.