Ripretinib vs Sunitinib for Gastrointestinal Stromal Tumor

(INSIGHT Trial)

Recruiting at 63 trial locations

Overseen By Clinical Team

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Deciphera Pharmaceuticals LLC

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: CNS metastases, Heart disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 48 months

54 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 3, 2-arm, randomized, open-label, global, multicenter study comparing the efficacy of ripretinib to sunitinib in participants with GIST who progressed on first-line treatment with imatinib, harbor co-occurring KIT exons 11+17/18 mutations, and are without KIT exon 9, 13, or 14 mutations. Upon disease progression as determined by an independent radiologic review, participants randomized to sunitinib will be given the option to either crossover to receive ripretinib 150 mg QD or discontinue sunitinib.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot use strong or moderate inhibitors or inducers of cytochrome P450 (CYP) 3A or consume grapefruit within 14 days before starting the study drug.

What data supports the effectiveness of the drug ripretinib for gastrointestinal stromal tumors?

Ripretinib is effective as a fourth-line treatment for gastrointestinal stromal tumors, showing increased progression-free survival compared to placebo in the INVICTUS trial. Although it is not superior to sunitinib in second-line treatment, it has a better safety profile with fewer severe side effects. ^{1 2 3 4 5}

Is Ripretinib generally safe for humans?

Ripretinib has a better safety profile compared to Sunitinib, with fewer severe side effects like high blood pressure. It is generally well-tolerated, with common side effects including increased lipase levels, fatigue, and low phosphate levels in the blood. ^{1 2 3 4 6}

What makes ripretinib unique compared to sunitinib for treating gastrointestinal stromal tumors?

Ripretinib is unique because it is designed to target a broad range of mutations that can develop resistance to other treatments, and it has a better safety profile with fewer severe side effects compared to sunitinib. ^{1 2 3 4 5}

Research Team

Clinical Team

Principal Investigator

Deciphera Pharmaceuticals, LLC

Eligibility Criteria

This trial is for adults over 18 with advanced Gastrointestinal Stromal Tumor (GIST) who have progressed after imatinib treatment and have specific KIT exon mutations. Participants must be in good enough health to perform daily activities, not pregnant, agree to use contraception, and cannot have had major surgery recently or certain heart conditions.

Inclusion Criteria

My GIST cancer has worsened despite being on imatinib.

Participants must have at least 1 measurable lesion according to mRECIST v1.1 within 21 days prior to the first dose of study drug

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

My cancer has a KIT mutation in exon 9, 13, or 14.

I have cancer that has spread to my brain.

I can take pills and do not have issues with absorbing food or need IV feeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ripretinib or sunitinib in 42-day cycles. Ripretinib is dosed continuously, while sunitinib is given for 4 weeks followed by a 2-week break.

Up to approximately 48 months

Crossover

Participants on sunitinib may crossover to receive ripretinib upon disease progression.

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 48 months

Treatment Details

Interventions

• Ripretinib
• Sunitinib

Trial Overview The study compares the effectiveness of two drugs: Ripretinib and Sunitinib in patients whose GIST has worsened despite initial therapy. It's a global test where people are randomly chosen to receive either drug. If Sunitinib fails, those patients can switch to Ripretinib.

Participant Groups

Group I: Ripretinib Experimental Treatment 1 Intervention

150 mg QD of ripretinib (3×50 mg tablets) will be dosed continuously in repeated 42-day cycles.

Group II: Sunitinib Active Control 1 Intervention

50 mg QD of sunitinib (4×12.5 mg capsules) will be dosed in 42-day cycles. Sunitinib will be given continuously for 4 weeks with a 2-week break.

Ripretinib is already approved in United States for the following indications:

Approved in United States as Qinlock for:

• Gastrointestinal stromal tumors (GIST) in adults who have previously received other medications, including imatinib

Who Is Running the Clinical Trial?

Deciphera Pharmaceuticals LLC

Lead Sponsor

Trials

17

Recruited

1,900+

Deciphera Pharmaceuticals, LLC

Lead Sponsor

Trials

19

Recruited

2,100+

Findings from Research

In the phase III INTRIGUE trial, ripretinib was found to be not superior to sunitinib for progression-free survival in patients with gastrointestinal stromal tumors.

Ripretinib demonstrated a better safety profile, resulting in fewer severe side effects (grade 3-4 toxicities), including lower rates of hypertension compared to sunitinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testing Ripretinib against Sunitinib in GIST. [2022]

Ripretinib is an effective treatment for gastrointestinal stromal tumors, showing increased progression-free survival compared to placebo in the pivotal phase III INVICTUS trial, and it works against a wide range of mutations in the KIT and PDGFRA genes.

The drug has an acceptable safety profile, with common serious side effects including increased lipase levels, hypertension, fatigue, and low phosphate levels, making it a valuable option for patients who have already undergone multiple lines of therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ripretinib: A Review in Gastrointestinal Stromal Tumours as Fourth-or Later-Line of Therapy. Fung, S., Shirley, M.[2022]

In the INTRIGUE trial, patients with advanced gastrointestinal stromal tumors (GIST) treated with ripretinib reported better health-related quality of life (HRQoL) compared to those treated with sunitinib, particularly at the 29-day assessments.

Patients receiving ripretinib also experienced a longer time without symptoms or severe treatment-related side effects, averaging 173 days compared to 126 days for those on sunitinib, suggesting ripretinib may offer a clinically meaningful benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes and tolerability in patients receiving ripretinib versus sunitinib after treatment with imatinib in INTRIGUE, a phase 3, open-label study. Gelderblom, H., Jones, RL., Blay, JY., et al.[2023]

Ripretinib demonstrated a higher objective response rate compared to sunitinib in patients with advanced gastrointestinal stromal tumors (GIST) who had previously been treated with imatinib, showing 23.9% versus 14.6% respectively.

Although ripretinib was not superior to sunitinib in terms of progression-free survival (PFS), it had a significantly better safety profile with fewer severe adverse events (41.3% for ripretinib vs. 65.6% for sunitinib), indicating it may be a more tolerable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ripretinib Versus Sunitinib in Patients With Advanced Gastrointestinal Stromal Tumor After Treatment With Imatinib (INTRIGUE): A Randomized, Open-Label, Phase III Trial. Bauer, S., Jones, RL., Blay, JY., et al.[2023]

Ripretinib is a new type II tyrosine switch control inhibitor that targets both activating and drug-resistant mutations in KIT and PDGFRA, making it a promising treatment for gastrointestinal stromal tumors, especially after previous treatments with other tyrosine kinase inhibitors.

The ongoing Phase III study (NCT03673501) is comparing the safety and efficacy of ripretinib to sunitinib in patients with advanced gastrointestinal stromal tumors, focusing on progression-free survival as the primary endpoint.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrigue: Phase III study of ripretinib versus sunitinib in advanced gastrointestinal stromal tumor after imatinib. Nemunaitis, J., Bauer, S., Blay, JY., et al.[2020]

Ripretinib shows promising efficacy in Chinese patients with advanced gastrointestinal stromal tumors (GIST), achieving a median progression-free survival of 7.2 months and an objective response rate of 18.4% as a fourth-line or later therapy.

The treatment was generally well-tolerated, with 94.9% of patients experiencing treatment-related adverse events, mostly mild (grade 1/2), and only 15.4% experiencing more severe (grade 3/4) adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Ripretinib in Chinese Patients with Advanced Gastrointestinal Stromal Tumors as a Fourth- or Later-Line Therapy: A Multicenter, Single-Arm, Open-Label Phase II Study. Li, J., Cai, S., Zhou, Y., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Testing Ripretinib against Sunitinib in GIST. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Ripretinib: A Review in Gastrointestinal Stromal Tumours as Fourth-or Later-Line of Therapy. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes and tolerability in patients receiving ripretinib versus sunitinib after treatment with imatinib in INTRIGUE, a phase 3, open-label study. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Ripretinib Versus Sunitinib in Patients With Advanced Gastrointestinal Stromal Tumor After Treatment With Imatinib (INTRIGUE): A Randomized, Open-Label, Phase III Trial. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Intrigue: Phase III study of ripretinib versus sunitinib in advanced gastrointestinal stromal tumor after imatinib. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Ripretinib in Chinese Patients with Advanced Gastrointestinal Stromal Tumors as a Fourth- or Later-Line Therapy: A Multicenter, Single-Arm, Open-Label Phase II Study. [2023]