About the Investigational Study
Potential participants will need to complete circulating tumor DNA (ctDNA) testing to confirm mutations after signing a pre-screening informed consent form (ICF).
Approximately 54 participants will be randomized in a 2:1 ratio to ripretinib 150 mg once daily (QD) (continuous dosing) or sunitinib 50 mg QD (4 weeks on, 2 weeks off).
Upon disease progression as determined by blinded IRR, randomized sunitinib patients may crossover to receive ripretinib.
The primary outcome measure is progression-free survival (PFS) based on blinded independent radiologic review (IRR) using modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1 – gastrointestinal stromal tumor (GIST)-specific.
Key secondary outcome measures are:
- Objective response rate (ORR) by blinded IRR using mRECIST v1.1
- Overall survival (OS)
About Deciphera Pharmaceuticals
Deciphera Pharmaceuticals is a commercial-stage biopharmaceutical company on a mission to deliver transformational medicines to patients. Headquartered in Waltham, Massachusetts, with research facilities in Lawrence, Kansas, we develop innovative science to provide hope to people living with cancer.
Inspired by patients, driven by science
We are focused on discovering, developing, and delivering important new medicines to patients for the treatment of cancer. Our commitment to patients is at the center of everything we do. We are dedicated. We are focused. We are motivated.
Please explore our website to find out more.
What Will Happen During the Study?
Pre-screening
Potential participants who sign the pre-screening ICF will undergo ctDNA testing to confirm their GIST mutation. A blood sample will be collected and sent to a central laboratory to determine mutation eligibility. Depending on local regulations, remote collection of the blood sample may be an option.
Screening
Potential participants with KIT exons 11+17/18 mutations and without exons 9, 13 or 14 mutations confirmed by ctDNA sample at pre-screening will continue to screening.
Randomization
Eligible participants will be randomized in a 2:1 ratio to receive open-label ripretinib or sunitinib in 6 week cycles.
Study Treatment
Participants randomized to ripretinib will be administered 150 mg once daily, dosed continuously during each 6-week cycle. Participants randomized to sunitinib will be administered 50 mg once daily, with 4 weeks of continuous dosing, followed by a 2-week break, during each 6-week cycle.
Crossover
Participants randomized to sunitinib who experience progressive disease will be given the option to crossover to receive ripretinib 150 mg once daily. Progressive disease will be determined by blinded IRR per mRECIST v1.1.
Who Can Participate?
Your patient may be eligible if he or she:
- Is ≥18 years of age
- Has a histologic diagnosis of GIST with co-occurring KIT exons 11 and 17 and/or 18 mutations confirmed by central laboratory ctDNA analysis at pre-screening
- Does not have a history of KIT exon 9 mutation
- Has advanced GIST and radiologic progression on imatinib treatment
- Has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2 at screening
- Has at least 1 measurable lesion according to mRECIST v1.1 within 21 days prior to the first dose of study drug
- Has adequate organ function and bone marrow reserve based on laboratory assessment performed at screening
- Has resolution of all toxicities from prior therapy to Grade ≤1 (or participant baseline) within 1 week prior to the first dose of study drug
- Meets all additional eligibility criteria at screening
What is Ripretinib?
Ripretinib is a typrosine kinase inhibitor that inhibits KIT proto-oncogene receptor tyrosine kinase (KIT) and platelet derived growth factor receptor A (PDGFRA) kinase, including wild type, primary and secondary mutations. Ripretinib also inhibits other kinases in vitro, such as PDGFRB, TIE2, VEGFR2, and BRAF.1
Ripretinib is indicated for the treatment of adult patients with advanced GIST who have received prior treatment with 3 or more kinase inhibitors, including imatinib. The recommended dose of ripretinib is 150 mg once daily with or without food until disease progression or unacceptable toxicity.1
In previous clinical trials, the most common adverse reactions (≥20%) were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar-plantar erythrodysesthesia, and vomiting.1
Ripretinib is not approved or indicated as a second-line agent for patients with advanced GIST previously treated with imatinib by the U.S. FDA or any other global regulatory agency.
1. QINLOCK® [package insert]. Waltham, MA: Deciphera Pharmaceuticals, LLC; 2023.
Frequently Asked Questions
- Where is the study taking place?
The INSIGHT study is global. You can find site location information on clinicaltrials.gov. You can also contact the sponsor if you have questions about the study, including potential travel support for your patient.
- How are the study drugs administered?
Both ripretinib and sunitinib are administered orally. Participants randomized to ripretinib will take 150 mg each day, dosed continuously in repeated 6-week cycles. Participants randomized to sunitinib will take 50 mg each day, with 4 weeks of continuous dosing, followed by a 2-week break, in repeated 6-week cycles.
- What is the study rationale?
An exploratory analysis was conducted from the phase III INTRIGUE study, comparing ripretinib vs. sunitinib in a second-line GIST setting, using baseline ctDNA. The subset analysis showed a mPFS of 14.2 months with ripretinib vs. 1.5 months with sunitinib [HR 0.22; 95%CI, 0.11-0.44; nominal P<0.0001] in patients with co-occurring KIT exons 11 + 17 and/or 18 mutations, excluding mutations in exon 9, 13, and/or 14.
Safety was consistent with the primary analysis of the phase III study.
These results provided the framework for the phase III INSIGHT study to formally investigate the efficacy and safety of ripretinib vs. sunitinib in patients with advanced GIST with KIT exon 11 + 17/18 mutations.
For More Information
For further information related to this study please contact MedicalInformation@Deciphera.com.