Pembrolizumab and Binimetinib in Treating Patients With Locally Advanced or Metastatic Triple Negative Breast Cancer

NCT03106415 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: MC1632NCI-2017-0049616-009051
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the best dose of pembrolizumab and binimetinib and how well it works when given together with pembrolizumab in treating patients with triple negative breast cancer that has spread to other parts of the body (metastatic). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and binimetinib may work better in treating patients with triple negative breast cancer.

Conditions

Breast Adenocarcinoma; Metastatic Triple-Negative Breast Carcinoma; Stage III Breast Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7; Stage IV Breast Cancer AJCC v6 and v7

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) of Pembrolizumab in Combination With Binimetinib Using the Standard 3+3 Design (Phase I)

  Will be assessed by Common Terminology Criteria for Adverse Events version 4.0. Safety/adverse events data will be tabulated, including adverse events of all grades.

  35 days

• Objective Response Rate (ORR) as (Phase II)

  Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST). Will utilize Simon's Two-Stage Optimal Design to test the null hypothesis. Will be estimated using the approach of Jung and Kim. The 90% lower confidence bound will be calculated using the approach of Koyama and Chen. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  3 years

Secondary Outcomes (3)

• ORR by Immune-related RECIST Criteria (irRECIST)

  Up to 3 years

• Progression Free Survival (PFS)

  The time from study enrollment to date of progression, assessed up to 3 years

• Overall Survival (OS)

  The time from study enrollment to death attributable to any cause, assessed up to 3 years

Study Arms (1)

Treatment (binimetinib, pembrolizumab)

EXPERIMENTAL

Patients receive binimetinib PO BID on days 1-14 of cycle 1 and on days 1-21 of cycle 2 and subsequent cycles. Beginning cycle 2, patients also receive pembrolizumab IV over 30 minutes on day 1. Cycle 1 equals 14 days. Cycles 2 and beyond repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Binimetinib; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

Interventions

Binimetinib DRUG

Given PO

Also known as: ARRY-162, ARRY-438162, MEK162, Mektovi

Treatment (binimetinib, pembrolizumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (binimetinib, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (binimetinib, pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• Age \>= 18 years
• Histological confirmation of adenocarcinoma of the breast
• Estrogen receptor (ER) and progesterone receptor (PR) negative; defined as ER =\< 10% and PR =\< 10% staining by immunohistochemistry (IHC)
• HER2 negative in the primary or metastatic tumor tissue defined as:
• Immunohistochemistry (IHC) grade 0 as defined by no staining observed or membrane staining that is incomplete and is faint/barely perceptible and within =\< 10% of the invasive tumor cell; OR
• IHC 1+ as defined by incomplete membrane staining that is faint/barely perceptible and within \> 10% of the invasive tumor cell; OR
• IHC grade 2+ staining intensity by means of IHC analysis with no gene amplification below; OR
• No gene amplification on in situ hybridization (ISH) based on:
• Single-probe average HER2 copy number \< 4.0 signals/cell OR
• Dual-probe HER2/CEP17 ratio \< 2.0 with an average HER2 copy number \< 4.0 signals/cell
• For phase II part of the trial: =\< 3 prior lines of treatment in the metastatic setting for the current breast cancer; however, there is no limit on number of prior line of therapy in phase I part of the trial
• Measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Hemoglobin \>= 9.0 g/dL (must be \>= 7 days after most recent transfusion) (obtained =\< 14 days prior to registration)
• Absolute neutrophil count (ANC) \>= 1500/mm\^3 or \>= 1.5 x 10\^9/L (obtained =\< 14 days prior to registration)

You may not qualify if:

• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm OR participated in a study of an investigational agent, received study therapy or used an investigational device =\< 4 weeks prior to registration
• Immunocompromised patients and patients with known immunodeficiency; or receiving systemic steroid therapy or any other immunosuppressive therapy =\< 7 days prior to registration; NOTE: inhaled steroids and low-dose corticosteroids are allowed
• History of active tuberculosis (TB), human immunodeficiency virus (HIV), active hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\] reactive) and/or active hepatitis C infection (e.g. hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] qualitative is detected)
• Received a live vaccine =\< 30 days prior to registration; NOTE: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines, and are not allowed
• Hypersensitivity to pembrolizumab, binimetinib, or any excipients of either drug
• Prior anti-cancer therapy with a monoclonal antibody (mAb) =\< 4 weeks prior to registration OR failure to recover (to =\< grade 1) from adverse events (AE) attributable to agents received \> 4 weeks prior to registration
• Prior therapy including chemotherapy, targeted small molecule therapy or radiation therapy =\< 2 weeks prior to registration OR failure to recover (to =\< grade 1 or to baseline) from adverse events (AE) attributable to agents received \> 4 weeks prior to registration; NOTE: exception for neuropathy =\< grade 2, which is allowed
• Any active central nervous system (CNS) lesion (i.e., those with radiographically unstable, symptomatic lesions) and/or leptomeningeal metastases; NOTE: patients treated with stereotactic radiotherapy or surgery are eligible if no evidence of CNS disease progression \>= 4 weeks and patients must be off corticosteroid therapy for \>= 3 weeks; NOTE: carcinomatous meningitis is excluded regardless of clinical stability
• Active autoimmune disease requiring systemic treatment in the past 2 years (i.e. use of disease modifying agents, corticosteroids or immunosuppressive drugs); NOTE: replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Known history of, or any evidence of active, non-infectious pneumonitis
• Active infection requiring systemic therapy

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

binimetinib; pembrolizumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Saranya Chumsri MD
• Organization: Mayo Clinic

Chumsri.Saranya@mayo.edu

904-953-2000

Study Officials

• Saranya Chumsri, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2017
• First Posted: April 10, 2017
• Study Start: September 27, 2017
• Primary Completion: May 19, 2022
• Study Completion: May 19, 2022
• Last Updated: June 27, 2025
• Results First Posted: August 20, 2024

Record last verified: 2024-10

Locations

US (1)