A Study of Ripretinib vs Sunitinib in Patients with Advanced Gastrointestinal Stromal Tumor (GIST) with Specific KIT Exon Mutations Who Were Previously Treated with Imatinib

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Deciphera Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 Nov 2023 → ongoing

Decision date (initial)

2023-08-21

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Deciphera Pharmaceuticals, LLC

External identifiers

EU CT number

2022-503058-37-00

ClinicalTrials.gov

NCT05734105

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic, Therapy

To compare the efficacy of ripretinib vs sunitinib as measured by progression-free survival (PFS) based on independent radiologic review (IRR) in this patient population (KIT exon 11+17/18 mutations)

Secondary objectives 6

1. To compare the objective response rate (ORR) by independent radiologic review (IRR) of ripretinib vs sunitinib using modified Response Evaluation Criteria in Solid Tumors v1.1 – GIST-specific (mRECIST)
2. To compare the overall survival (OS) of ripretinib vs sunitinib
3. To compare quality of life (QoL) during treatment as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer 30-item (EORTC-QLQ-C30), select items from the National Cancer Institute Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (NCI-PRO-CTCAE), and the EuroQol 5‑Dimension 5‑Level (EQ-5D-5L) of ripretinib vs sunitinib
4. To compare disease control rate (DCR) by IRR, time-to-progression (TTP) by IRR, PFS based on Investigator assessment, duration of response (DOR) by IRR, and time-to-response (TTR) by IRR of ripretinib vs sunitinib
5. To assess the safety profiles of ripretinib vs sunitinib
6. To assess progression-free survival 2 (PFS2) and second PFS by Investigator assessment

Conditions and MedDRA coding

Advanced Gastrointestinal Stromal Tumor

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Male or female ≥18 years of age.
2. Histologic diagnosis of GIST with co-occurring KIT exons 11+17/18 mutations confirmed by ctDNA sample analyzed by the central laboratory at pre-screening
3. Participants must have advanced GIST and radiologic progression on imatinib treatment. Imatinib treatment must have been discontinued at least 5 days prior to the first dose of study drug. All prior imatinib treatment will count as 1 line of therapy (eg, adjuvant imatinib and dose escalation of imatinib).
4. ECOG PS of ≤2 at screening.
5. Female participants of childbearing potential must have a negative serum beta-human chorionic gonadotrophin pregnancy test at screening and a negative pregnancy test at Cycle 1 Day 1 prior to the first dose of study drug.

Exclusion criteria 5

1. Presence of co-occurring KIT exons 11+17 and/or 18 mutations that cannot be confirmed by central laboratory testing of ctDNA at pre-screening.
2. History of KIT exon 9 mutation or detection of KIT exons 9, 13, or 14 mutation in a ctDNA sample by the central laboratory at pre-screening.
3. Treatment with any other line of therapy in addition to imatinib for advanced GIST. Imatinib containing combination therapy in the first-line setting is not allowed.
4. A prior or concurrent malignancy whose natural history or treatment have the potential to interfere with the safety or efficacy assessment of this clinical study are not eligible. For example, participants receiving adjuvant cancer treatment are not eligible if those medications are potentially active against GIST or excluded per protocol. NOTE: Participants with a history of breast cancer, requiring continued hormonal treatment (eg, anti-estrogen or an aromatase inhibitor) may continue treatment. Participants with a history of prostate cancer, requiring continued support with luteinizing hormone-releasing hormone agonists, with or without androgens, may continue treatment.
5. Has known active central nervous system metastases.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS based on IRR per mRECIST, which is defined as the time from randomization until documented progressive disease (PD) based on IRR per mRECIST or death due to any cause, whichever occurs first.

Secondary endpoints 9

1. To compare ORR by IRR of ripretinib vs sunitinib using mRECIST
2. To compare OS of ripretinib vs sunitinib
3. Summary measures from the EORTC-QLQ-C30, NCI-PRO-CTCAE items (questions number 15 “constipation”, 16 “diarrhea”, 30 “hand-foot syndrome”, and 53a and b “fatigue”), and the EQ-5D-5L
4. Time-to-progression based on IRR per mRECIST, which is defined as the time from randomization until documented progressive disease based on IRR per mRECIST
5. Disease control rate at 6, 12, 18, and 24 weeks based on IRR per mRECIST, which is defined as the proportion of participants who achieve complete response (CR), partial response (PR), or stable disease (SD) at the specified time point based on IRR per mRECIST
6. Progression-free survival based on the Investigator per mRECIST, which is defined as the time from randomization until documented PD based on Investigator’s assessment per mRECIST or death due to any cause, whichever occurs first
7. Duration of response for participants who achieve confirmed CR or PR, defined as the time interval from the time that the measurement criteria are first met for confirmed CR or confirmed PR (whichever is first recorded) until the first date the PD is objectively documented or death, whichever occurs first
8. Time-to-response is defined as the time from date of randomization until the first assessment of confirmed CR or PR per mRECIST
9. PFS2, which is defined as the time from randomization until PD on next-line treatment as determined by the Investigator, or death due to any cause, whichever occurs first − Second PFS, which is defined as the date of the first dose of next-line treatment until PD based on Investigator assessment or death due to any cause, whichever occurs first

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Deciphera Pharmaceuticals Inc.

Sponsor organisation

Deciphera Pharmaceuticals Inc.

Address

200 Smith Street

City

Waltham

Postcode

02451-0099

Country

United States

Scientific contact point

Organisation

Deciphera Pharmaceuticals Inc.

Contact name

Clinical trial information

Public contact point

Organisation

Deciphera Pharmaceuticals Inc.

Contact name

Clinical trial information

Third parties 16

Locations

8 EU/EEA countries · 29 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 86 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

19 submissions — initial application plus substantial / non-substantial modifications