This research is being done to evaluate the safety and effectiveness of a drug currently known as VS-6766 in combination with the drugs abemaciclib and fulvestrant in HR+/HER2-negative breast cancer.
The names of the study drugs involved in this study are:
* VS-6766 * Abemaciclib * Fulvestrant
Participants must have histologically or cytologically confirmed hormone receptor positive (HR+), HER2 negative metastatic or locally recurrent unresectable invasive breast cancer. ER, PR and HER2 measurements should be performed according to institutional guidelines, in a CLIA-approved setting. Cut-off values for positive/negative staining should be in accordance with current ASCO/CAP (American Society of Clinical Oncology/College of American Pathologists) guidelines.
Participants may have measurable or non-measurable disease according to RECIST v1.1.
Men and pre- and postmenopausal women are eligible. Ongoing monthly GNRH agonist is required in pre-menopausal women or male participants for at least 4 weeks prior to study entry. If men or pre-menopausal women have not received regular GNRH agonist for at least 4 weeks prior to study entry, these patients will be excluded.
Participants must have radiological or objective evidence of progression on any CDK 4/6 inhibitor-containing regimen in the metastatic setting, and/or relapse/progression during or within 12 months of completion of any CDK4/6 inhibitor-containing regimen in the adjuvant setting.
Participants with active brain metastases or with known carcinomatous meningitis. Stable, treated brain metastases are allowed (this includes participants who have documented radiologic stability at least 4 weeks after radiotherapy, and do not require systemic steroids for management of symptoms from CNS metastatic lesions). Any patients with documented brain metastasis not meeting above criteria for stable treated brain metastasis are considered to have active brain metastases.
Phase I: Participants who have discontinued prior abemaciclib for toxicity, at any dose. Phase II: Participants who have discontinued prior abemaciclib for toxicity, if that toxicity occurred at or above the RP2 dose level for abemaciclib that is incorporated into phase II of this trial.
Participants who have discontinued prior fulvestrant for toxicity.
Prior treatment with any MEK inhibitor.
Sequential
VS-6766
DrugTaken Orally
Abemaciclib
DrugTaken Orally
Fulvestrant
DrugAdministered by intramuscular injection
Phase 1 Maximum tolerated dose (MTD)
Determine maximum tolerated dose (MTD) of VS-6766 in combination with abemaciclib and fulvestrant using Bayesian Optimal Interval Design
Phase 1 Recommended Phase II Dose (RP2D)
Determine Recommended Phase II Dose (RP2D) of VS-6766 in combination with abemaciclib and fulvestrant using Bayesian Optimal Interval Design
Phase 2 Clinical benefit rate (CBR)
The primary endpoint in phase II is assessment of the clinical benefit rate (CBR; complete response + partial response + stable disease for \>/=24 weeks)
Overall response rate (ORR)
Assess overall response rate (ORR) defined as confirmed complete response or partial response per RECIST 1.1.
Progression-free survival (PFS)
Assess progression-free survival (PFS) defined as as the time from study registration to radiographic or clinical evidence of disease progression or death due to any cause, whichever occurred first. Patients alive without disease progression are censored at the date of last disease evaluation.
Overall survival (OS)
Assess Overall survival (OS) defined as time from randomization (or registration) to death due to any cause, or censored at date last known alive.
Treatment Related Adverse Events
Assess safety through number of Treatment Related Adverse Events per CTCAE v5.0
Click on the lead sponsor to view all of their trials.
Adrienne G. Waks
Lead sponsor
Dana-Farber Cancer Institute
Sponsor institution
Verastem, Inc.
Collaborator
Eli Lilly and Company
Collaborator
