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

Plain-language summary

This study evaluated CGT9486 alone and in combination with Pexidartinib or Sunitinib in participants with advanced solid tumors. It enrolled patients over 18 whose disease had progressed despite standard therapy or who had no effective standard treatment. It was a Phase 1/Phase 2 study and has been completed.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

PHASE1/PHASE2

Status

Completed

Sponsor

Cogent Biosciences, Inc.

Intervention

CGT9486, Pexidartinib, Sunitinib

Start date

3/6/2015

Estimated completion

5/11/2020

Countries

United States

Related genes

Locations

• Miami, United States
• Boston, United States
• Ann Arbor, United States
• Detroit, United States
• New York, United States
• Columbus, United States

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

Inclusion Criteria:

* 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).

Exclusion Criteria:

* 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