Testing the Combination of the Anticancer Drugs ZEN003694 and Binimetinib in Patients With Advanced/Metastatic or Unresectable Solid Tumors With RAS Alterations and Triple Negative Breast Cancer

ConditionsAdvanced Malignant Solid Neoplasm Metastatic Malignant Solid Neoplasm Refractory Malignant Solid Neoplasm Triple-Negative Breast Carcinoma Unresectable Malignant Solid Neoplasm

Trial statusRecruiting

Trial phasePhase 1

Trial typeInterventional

Biological sexAll

Age18+

SponsorNational Cancer Institute (NCI)

About this trial

This phase I trial tests the safety, side effects, and best dose of ZEN003694 in combination with binimetinib in treating patients with solid tumors that carry RAS alterations and that have spread to other places in the body (advanced/metastatic) or cannot be removed by surgery (unresectable). ZEN003694 is an oral medication with potential anticancer activity. It is an inhibitor of a family of proteins called bromodomain and extra-terminal (BET) which play important role during development and cellular growth. ZEN003694 may stop the growth of tumor cells that produce BET. Binimetinib is in a class of medications called kinase inhibitors. It works by blocking the action proteins called MEK1 and MEK2, that signal cancer cells to multiply. It may help keep cancer cells from growing and spreading. There is pre-clinical evidence that using ZEN003694 and binimetinib together may shrink or stabilize cancers studied in this trial. There are two parts of this study; dose escalation and dose expansion. In the dose escalation part of this study, different people will get different doses of the study drugs ZEN003694 and binimetinib. In the dose expansion part of this study, the highest dose with manageable side effects will be given to additional people. This will help to understand the side effects that may happen with this drug combination.

Eligibility criteria

Qualifiers

Patients must have histologically confirmed advanced/metastatic or unresectable solid tumor that is refractory to standard therapy or has relapsed after standard therapy

For Part 1 and 2 -

Triple negative breast cancer (TNBC) (estrogen receptor =< 1%, progesterone receptor =< 1%, human epidermal growth factor receptor 2 0-1+ or non-amplified)

Solid tumor with genomic alteration(s) activating RAS signaling including activating KRAS, NRAS, HRAS, or BRAF mutations, inactivating NF1 mutations, or BRAF fusions

Disqualifiers

Patients who have not recovered from adverse events (AEs) due to prior anticancer therapy (i.e., have residual toxicities > Grade 1) with the exception of alopecia, peripheral neuropathy, and endocrinopathy managed with replacement therapy before the initiation of study treatment

Patients who are receiving any other investigational agents

Breast cancer patients with a prior history of hormone receptor positivity will not be eligible

Patients with known PI3K pathway activating genomic alterations including inactivating mutations/deletions in PTEN and PIK3R1, amplifications in PIK3CA, and activating mutations in PIK3CA, Akt, or mTOR will not be eligible

Trial design

Treatments tested in this trial

BET Bromodomain Inhibitor ZEN-3694
Binimetinib
Biopsy Procedure
Biospecimen Collection
Computed Tomography
Magnetic Resonance Imaging

Treatment groups

42 Participants

are divided into 1 treatment group

Sponsors and collaborators

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov