CGT9486 (Formerly Known as PLX9486) as a Single Agent and in Combination With PLX3397 (Pexidartinib) or Sunitinib in Participants With Advanced Solid Tumors

Completed · Phase 1/Phase 2

Conditions studied: Gastrointestinal Stromal Tumors

In brief

The goal of this clinical research study is to learn how CGT9486 (fka PLX9486) may affect cancer cells with certain mutations in the KIT gene, specifically in participants with types of advanced solid tumors including gastrointestinal stromal tumor (GIST). CGT9486 (fka PLX9486) is designed to block KIT gene mutations. These mutations can cause cancer and cancer cell growth. By blocking these mutations, the drug may kill the cancer cells with the mutation and/or stop the tumor from growing. By combining CGT9486 (fka PLX9486) with PLX3397 and CGT9486 (fka PLX9486) with sunitinib, the investigators hope to block most KIT gene mutations that drive cancer growth.

Key facts

Study ID

NCT02401815

Run by

Cogent Biosciences, Inc.

People needed

51

Starts

2015-03-06

Expected to finish

2020-05-11

Last updated by the study team

2025-02-14

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Male or female ≥18 years old.
• Part 1, Part 2b, Part 2d, and Part 2e: Participants with advanced solid tumors who have tumor progression following standard therapy, have treatment-refractory disease, or for whom there is no effective standard of therapy.
• Part 2d: Participants with non GIST solid tumors with KIT mutations, who are TKI naïve or have been previously treated with KIT directed TKI therapy who are appropriate for KIT directed TKI therapy
• Part 2a, Part 2c, and Part 2f (GIST participants): Histologically confirmed locally advanced, metastatic and/or unresectable GIST.
• Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test at Screening (≤7 days prior to the first dose of study drug) and must agree to use an effective form of contraception from the time of the negative pregnancy test up to 6 months after the last dose of study drug.
• Fertile men must agree to use an effective method of birth control during the study and for up to 6 months after the last dose of study drug.
• All associated toxicity from previous or concurrent cancer therapy must be resolved (to ≤ Grade 1 or Baseline) prior to study treatment administration.
• Willing and able to provide written informed consent prior to any study related procedures and to comply with all study requirements.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
• Life expectancy ≥3 months.
• Adequate hematologic, hepatic, and renal function:
• Left ventricular ejection fraction (LVEF) >50% per echocardiogram (ECHO) or multiple-gated acquisition (MUGA) for participants on the sunitinib arms (Parts 2e and f).

You may not qualify if…

• Known or demonstrated wild type KIT or platelet-derived growth factor receptors (PDGF-R), or known or demonstrated mutations of PDGF R, sorbitol dehydrogenase (SDH), or neurofibromin 1 (NF 1) that are causative for the observed malignancy.
• For Part 1 (phase 1, single agent): Participants with a known or presumed pathogenic KIT exon 13 or 14 resistance mutation.
• Parts 2a and 2d: Participants with known or presumed pathogenic KIT exon 13 or 14 resistance mutations. (However, such participants are permitted on the combination arms of Parts 2b, 2c, 2e, or 2f.)
• Presence of symptomatic or uncontrolled brain or central nervous system metastases. Participants with stable, treated brain metastases are eligible for this trial. However, participants must not have required steroid treatment for their brain metastases within 30 days of Screening.
• Known or suspected allergy to the investigational agent or any agent given in association with this trial.
• Clinically significant cardiac disease
• Inability to take oral medication or significant nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption.
• Ongoing infection of ≥ Grade 2 severity.
• Non-healing wound, ulcer, or bone fracture.
• Known human immunodeficiency virus (HIV)-positive individuals on combination antiretroviral therapy, participants with known active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy
• Hepatobiliary diseases including biliary tract diseases, autoimmune hepatitis, inflammation, fibrosis, or cirrhosis of liver caused by viral, alcohol, or genetic reasons. Gilbert's disease is allowed if total bilirubin is ≤1.5 * upper limit of normal (ULN).
• Interstitial lung disease with ongoing signs and symptoms at the time of informed consent.
• Females who are pregnant or nursing.
• Any psychological, familial, sociological, or geographical condition that could hamper compliance with the study protocol.
• Strong CYP3A4 inhibitors or inducers within 14 days or 5 drug half-lives of the agent, whichever is longer, of study drug initiation or the need to continue these drugs during this study.
• Major surgery or significant traumatic injury within 14 days of Cycle 1 Day 1.
• History (within 2 years prior to first study drug administration) of another malignancy unless the malignancy was treated with curative intent and likelihood of relapse is small (<5% in 2 years in the judgment of the investigator).
• Anti-cancer therapy within the period immediately before Cycle 1 Day 1

Where it is running

• Sylvester Comprehensive Cancer Center/ UMHC — Miami, Florida, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States
• University of Michigan Comprehensive Cancer Center — Ann Arbor, Michigan, United States
• Karmanos Cancer Institute — Detroit, Michigan, United States
• Memorial Sloan Kettering Cancer Center — New York, New York, United States
• OSU Comprehensive Cancer Center — Columbus, Ohio, United States

Full record on ClinicalTrials.gov

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