Ripretinib vs Sunitinib for Gastrointestinal Stromal Tumor

(INSIGHT Trial)

Not currently recruiting at 76 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, ripretinib and sunitinib, for individuals with gastrointestinal stromal tumors (GIST) that have specific genetic mutations and have worsened after initial treatment. The goal is to determine which treatment more effectively slows tumor growth. Suitable candidates have GIST with specific genetic markers and have experienced progression after using imatinib. If tumors worsen on sunitinib, participants may switch to ripretinib. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that ripretinib is generally well-tolerated by patients with advanced gastrointestinal stromal tumors (GIST). Some side effects may occur, but they are often manageable. The FDA has approved ripretinib for advanced GIST, reflecting a strong safety record based on current data.

Similarly, studies indicate that sunitinib is generally well-tolerated, though it may cause side effects like tiredness and high blood pressure. With careful monitoring, many patients can continue treatment.

Both treatments have undergone thorough study, and their safety is well-documented. However, as with any medication, individual experiences can vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Ripretinib is unique because it targets the switch control mechanism of tyrosine kinases, which is different from how most current treatments for gastrointestinal stromal tumors (GIST), like Sunitinib, work. This novel mechanism allows Ripretinib to inhibit a broader range of mutations that drive tumor growth. Researchers are excited about Ripretinib because it offers the potential for more effective control of resistant tumor forms, providing hope for patients who might not respond well to existing therapies.

What evidence suggests that this trial's treatments could be effective for gastrointestinal stromal tumor?

This trial will compare Ripretinib and Sunitinib for treating gastrointestinal stromal tumors (GIST). Research has shown that Ripretinib may effectively treat GIST, shrinking tumors in 11.8% of patients in earlier studies. It also appears safer than Sunitinib, the standard treatment option in this trial. Although Sunitinib has been the standard, Ripretinib might offer similar efficacy with improved safety. Overall, Ripretinib could be a suitable option for those who have already tried other treatments like Imatinib. ^{6 7 8 9 10}

Who Is on the Research Team?

Clinical Team

Principal Investigator

Deciphera Pharmaceuticals, LLC

Are You a Good Fit for This Trial?

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

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

My GIST cancer has worsened despite being on imatinib.

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

I have cancer that has spread to my brain.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

Citations

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QINLOCK also demonstrated a confirmed objective response rate of 11.8% versus 0% in the placebo arm compared to rates of 9.4% versus 0% in the ...

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Patients with advanced GIST receiving ripretinib in the UK within the EAP reported prolonged benefits, in line with the recent phase III clinical trials.

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pubmed.ncbi.nlm.nih.gov

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