Phase 3 Study Evaluates Ripretinib for KIT Exon 11-Mutated GIST

The pivotal phase 3 INSIGHT trial will assess the ripretinib (Qinlock) compared with sunitinib (Suntent) for the treatment of patients with gastrointestinal stromal tumor (GIST) who progressed on first-line treatment with imatinib and harbor co-occurring KIT exons 11+17/18 mutations.¹

The launch of INSIGHT is a result of positive findings from the ctDNA analysis of the phase 3 INTRIGUE study (NCT03673501). In INTRIGUE, ripretinib showed better disease control compared with sunitinib in the KIT exon 11 intent-to-treat population. The ORR in the subgroup was 23.9% with ripretinib compared with 14.6% in the sunitinib arm (95% CI, 0.7-17.8; nominal P = .03).

"Ripretinib has a dual mechanism of action binding to the kinase switch pocket and the activation loop. The addition of ripretinib to the NCCN guidelines is very important, as it provides patients with metastatic GIST a very effective and tolerable treatment," Robin Jones, MD, BSc, MB BS, MRCP, consultant medical oncologist and head of the sarcoma unit at The Royal Marsden, told Targeted Oncology^TM.

INSIGHT is an international phase 3, randomized, open-label, global, multicenter study where investigators are comparing the efficacy of ripretinib with sunitinib in this patient population.²

Those enrolled in the study consist of patients without KIT exon 9, 13, or 14 mutations who are aged 18 years or older, have advanced GIST and radiologic progression on imatinib treatment, an ECOG performance status of 0-2, at least 1 measurable lesion according to mRECIST v1.1 within 21 days prior to the first dose of study drug, and adequate organ function and bone marrow reserve. Additionally, patients must all have resolved from their toxicities from prior therapy to grade ≤1 within 1 week prior to the first dose of treatment.

For female patients who are of childbearing potential, a negative pregnancy test must be obtained at the time of screening and prior to the first dose of the study treatment. Patients of reproductive potential must agree to follow contraception requirements.

Patients will be randomized to receive either 150 mg daily of ripretinib which will be dosed continuously in repeated 42-day cycles or 50 mg daily of sunitinib in 42-day cycles which will be given continuously for 4 weeks with a 2-week break. Upon disease progression as determined by an independent radiologic review, patients randomized to sunitinib will be given the option to either crossover to receive ripretinib150 mg QD or discontinue sunitinib.

The primary end point of the trial is progression-free survival and the secondary end points are objective response rate and overall survival.

The study is anticipated to start in August 2023 with an estimated enrollment of 54 patients.

In March 2023, a breakthrough therapy designation was granted to ripretinib (Qinlock) by the FDA for the treatment of adult patients with unresectable or metastatic gastrointestinal stromal tumor (GIST) who received prior treatment with imatinib (Gleevec) and harbor a KIT exon 11 mutation and co-occurring KIT exon 17 and/or 18 mutations.¹

"I hope the Phase 3 INSIGHT trial will lead to the approval of ripretinib as second-line therapy for patients most likely to benefit," added Jones.

REFERENCES:

Deciphera Pharmaceuticals announces QINLOCK® included in NCCN Guidelines® for the treatment of second-line GIST patients and FDA grants breakthrough therapy designation for QINLOCK in second-line GIST patients with mutations in KIT Exon 11 and 17/18. News release. Deciphera Pharmaceuticals. March 14, 2023. March 17, 2023. https://bit.ly/3ZQDEnj

A phase 3 study of ripretinib vs sunitinib in patients with advanced GIST with specific KIT exon mutations who were previously treated with imatinib (INSIGHT). ClinicalTrials.gov. Updated March 3, 2023. Accessed March 17, 2023. https://clinicaltrials.gov/ct2/show/NCT05734105?term=INSIGHT+ripretinib&draw=2&rank=1