Deciphera Announces Publication of the INVICTUS Pivotal Phase 3 Study of QINLOCK™ (ripretinib) in The Lancet Oncology
WALTHAM, Mass.: Deciphera Pharmaceuticals, Inc. today announced that The Lancet Oncology has published results from the INVICTUS pivotal Phase 3 study of QINLOCK in patients with fourth-line gastrointestinal stromal tumor (GIST). The INVICTUS study met its primary endpoint, demonstrating a statistically significant improvement in progression-free survival (PFS) in patients randomized to QINLOCK compared with patients receiving placebo. The safety profile observed in INVICTUS was consistent with previously published results, and results from the study were previously presented at the European Society of Medical Oncology Congress in September 2019.
“Resistance to approved inhibitors of KIT and PDGFRα remains a clinical challenge in advanced GIST,” said lead author Jean-Yves Blay, MD, Ph.D., Centre Léon Bérard, Unicancer, and Université Claude Bernard. “Our findings demonstrate that QINLOCK exhibited a favorable safety profile and significantly improved PFS over placebo in advanced GIST patients who have received three prior therapies. QINLOCK, a TKI whose activity is not restricted to a specific GIST mutation, establishes a new standard of care for the treatment of fourth-line GIST.”
“This publication in Lancet Oncology further validates Deciphera’s switch-control TKI approach and demonstrates QINLOCK’s efficacy in treating patients with fourth-line GIST, a patient population who until the recent U.S. FDA approval of QINLOCK, did not have an approved treatment option,” said Matthew L. Sherman, MD, Executive Vice President and Chief Medical Officer of Deciphera. "By broadly inhibiting KIT and PDGFRα kinase signaling through a dual mechanism of action that locks the kinase in the inactive state, QINLOCK prevents downstream signaling and cell proliferation.”
The article, entitled "Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial" is now available online and will be published in a future print issue of The Lancet Oncology. The publication can be accessed at the following link: http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30168-6/fulltext. The journal also published online a companion Comment article, "A new approach to refractory gastrointestinal stromal tumours with diverse acquired mutations,” by Toshirou Nishida, Department of Surgery, National Cancer Center Hospital, Tokyo, Japan and Toshihiko Doi, Department of Experimental Therapeutics, National Cancer Center, Hospital East, Chiba, Japan.
INVICTUS Phase 3 Study
INVICTUS is a Phase 3 randomized, double-blind, placebo-controlled, international, multicenter clinical study evaluating the safety, tolerability, and efficacy of QINLOCK compared to placebo in 129 patients with advanced GIST whose previous therapies have included imatinib, sunitinib, and regorafenib. Patients were randomized 2:1 to either 150 mg of QINLOCK or placebo once daily.
Results of the study were as follows:
- QINLOCK demonstrated a median PFS of 6.3 months compared to 1.0 month in the placebo arm and significantly reduced the risk of disease progression or death by 85% (hazard ratio of 0.15, p<0.0001).
- QINLOCK demonstrated a median overall survival of 15.1 months compared to 6.6 months in the placebo arm and reduced the risk of death by 64% (hazard ratio of 0.36).
- The most common adverse reactions (≥20%) were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar-plantar erythrodysesthesia syndrome (PPES), and vomiting. Adverse reactions resulting in permanent discontinuation occurred in 8% of patients, dosage interruptions due to an adverse reaction occurred in 24% of patients and dose reductions due to an adverse reaction occurred in 7% of patients who received QINLOCK.
GIST is cancer affecting the digestive tract or nearby structures within the abdomen, most often presenting in the stomach or small intestine. GIST is the most common sarcoma of the gastrointestinal tract, with approximately 4,000 to 6,000 new GIST cases each year in the United States and a similar incidence rate in the rest of the world. Most cases of GIST are driven by a spectrum of mutations. The most common primary mutations are in KIT kinase, representing approximately 80% of cases, or in PDGFRα kinase, representing approximately 6% of cases. Current therapies are unable to inhibit the full spectrum of primary and secondary mutations that drive resistance and disease progression. Estimates for 5-year survival range from 48% to 90%, depending on the stage of the disease at diagnosis.