VS-6766+Abema+Fulv in Met HR+/HER- BC

NCT05608252 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 22-490
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Breast Cancer; Hormone Receptor-positive Breast Cancer; Hormone Receptor Positive HER-2 Negative Breast Cancer

Keywords

Breast Cancer; Hormone Receptor-positive Breast Cancer; Hormone Receptor Positive HER-2 Negative Breast Cancer

Outcome Measures

Primary Outcomes (3)

• 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

  4 Weeks up to 2 years

• 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

  4 Weeks up to 2 years

• 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)

  6 months up to 3 years

Secondary Outcomes (8)

• Overall response rate (ORR)

  6 months up to 3 years

• Progression-free survival (PFS)

  6 months up to 3 years

• Overall survival (OS)

  6 months up to 10 years

• Treatment Related Adverse Events

  1 week up to 3 years

• Phase I Cmax of VS-6766

  16 days

Study Arms (2)

Phase 1 Dose Escalation

EXPERIMENTAL

During 28 day/4 week study cycle, participants will receive: * VS-6766 2x weekly for 3 out of the 4 week cycle * Abemaciclib 2x daily * Fulvestrant on day 1 of each study cycle (and day 15 of cycle 1 only)

Drug: VS-6766; Drug: Abemaciclib; Drug: Fulvestrant

Phase 2 Dose Expansion

EXPERIMENTAL

Participants will receive VS-6766 with abemaciclib and fulvestrant at the recommended phase II doses determined in the phase I portion of the study.

Drug: VS-6766; Drug: Abemaciclib; Drug: Fulvestrant

Interventions

VS-6766 DRUG

Taken Orally

Phase 1 Dose Escalation; Phase 2 Dose Expansion

Abemaciclib DRUG

Taken Orally

Also known as: Verzenio

Phase 1 Dose Escalation; Phase 2 Dose Expansion

Fulvestrant DRUG

Administered by intramuscular injection

Also known as: Faslodex

Phase 1 Dose Escalation; Phase 2 Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• It is not mandatory to have a CDK4/6 inhibitor-containing regimen as the most recent treatment.
• Participants must have radiological or objective evidence of progression on fulvestrant (as a single agent or as a component of any multi-drug regimen) in the metastatic setting.
• It is not mandatory to have a fulvestrant-containing regimen as the most recent treatment.
• Prior therapy:
• No more than two prior chemotherapy regimens in the metastatic setting.
• For both the phase I and phase II portions of this trial, there is no limit on prior lines of endocrine therapy in the adjuvant or metastatic setting.
• For phase 2 cohort only: Willing to undergo pre- and on-treatment tumor biopsies. Patients are exempt from this requirement if, in the opinion of the investigator, the biopsy procedure would pose a significant risk. Biopsies are optional in the phase 1 cohort.
• ECOG performance status \<2.
• Participants must have normal organ and marrow function as defined below:
• absolute neutrophil count ≥ 1.5 x 109/L
• platelets ≥100,000/μl

You may not qualify if:

• 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.
• The subject has received another investigational agent within at least 30 days or 5 half-lives of the first dose of study drug, whichever is longer, or is currently enrolled in any medical device research or other research that is judged by the sponsor to not be scientifically or medically compatible with this study.
• The subject has received a chemotherapy agent or immunotherapy within 21 days of the first dose of study drug.
• The subject has received an endocrine or biologic agent within 14 days of the first dose of study drug.
• The subject has completed radiation within 14 days of registration. Patients who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy.
• The subject has had major surgery within 14 days of registration.
• Participants with the following pre-existing ocular pathology are excluded:
• Patients with history of glaucoma, history of retinal vein occlusion (RVO), predisposing factors for RVO, including uncontrolled hypertension, uncontrolled diabetes.
• Patient with history of retinal pathology or evidence of visible retinal pathology that is considered a risk factor for RVO, intraocular pressure \> 21 mm Hg as measured by tonometry, or other significant ocular pathology, such as anatomical abnormalities that increase the risk for RVO.
• Patients with a history of corneal erosion (instability of corneal epithelium), corneal degeneration, active or recurrent keratitis, and other forms of serious ocular surface inflammatory conditions.
• History of rhabdomyolysis or neuromuscular disorders that are associated with elevated CK (eg inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
• The patient has an uncontrolled intercurrent illness including, but not limited to, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, congestive heart failure (New York Heart Association Class III or IV), active ischemic heart disease, myocardial infarction within the previous six months, syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), uncontrolled diabetes mellitus, severe obstructive pulmonary disease, or severe chronic liver or renal disease, or sudden cardiac arrest.

Sponsors & Collaborators

• Adrienne G. Waks: lead
• Verastem, Inc.: collaborator
• Eli Lilly and Company: collaborator

Study Sites (3)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

WITHDRAWN

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Dana Farber Cancer Institite

Boston, Massachusetts, 02115, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

abemaciclib; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Adrienne G Waks, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Adrienne G Waks, MD

CONTACT

617-632-3800; Adrienne_waks@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 27, 2022
• First Posted: November 8, 2022
• Study Start: February 23, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (3)