Ripretinib in Combination With Binimetinib in Patients With Gastrointestinal Stromal Tumor (GIST)

Deciphera

Status and phase: Withdrawn; Phase 2; Phase 1

Conditions: Gastrointestinal Stromal Tumors

Treatments: Drug: Ripretinib; Drug: binimetinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT05080621

DCC-2618-01-008

Details and patient eligibility

About

Multicenter, open-label Phase 1b/2 study of ripretinib in combination with binimetinib in patients with gastrointestinal stromal tumor (GIST). There will be 2 distinct parts in this study: Dose Escalation (Phase 1) and Expansion (Phase 2).

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients ≥18 years of age with advanced GIST (unresectable or metastatic).
2. Must have at least progressed on imatinib or have documented intolerance to imatinib.
3. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
4. Patients must have a histologic diagnosis of GIST.
5. If a female of childbearing potential, must have a negative pregnancy test.
6. Adequate organ function and bone marrow function

Exclusion criteria

1. Received prior anticancer therapy within 14 days or 5× the half-life whichever is longer) prior to the first dose.

2. Ongoing or prior participation in the DCC-2618-03-002 study.

3. Prior therapy with ripretinib.

4. Prior therapy with MEK inhibitor.

5. History of certain ocular disorders.

6. History of clinically significant hepatobiliary disease.

7. Known active central nervous system metastases.

8. History or presence of clinically relevant cardiovascular abnormalities.

9. Systemic arterial or venous thrombotic or embolic events within 6 months of first dose.

10. History of acute or chronic pancreatitis

11. History of chronic inflammatory bowel disease or Crohn's disease requiring intervention within 12 months of first dose.

12. Gastrointestinal abnormalities including but not limited to:

    • inability to take oral medication,
    • malabsorption syndromes

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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0 participants in 2 patient groups

Escalation

Experimental group

Description:

Escalation Phase: Increasing doses of ripretinib in combination with increase doses of binimetinib in patients with advanced GIST who have progressed on at least imatinib or are intolerant to imatinib and are ripretinib naïve in repeated 28-day cycles. Participants may remain on treatment until disease progression, unacceptable toxicity, or withdrawal of consent

Treatment:

Drug: binimetinib

Drug: Ripretinib

Expansion

Experimental group

Description:

Ripretinib in combination with binimetinib at the recommended Phase 2 dose (RP2D) in patients with advanced GIST who have progressed on imatinib or are intolerant to imatinib and are naïve. Participants may remain on treatment until disease progression, unacceptable toxicity, or withdrawal of consent

Treatment:

Drug: binimetinib

Drug: Ripretinib