Evaluation of Lasofoxifene Combined With Abemaciclib in Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation

NCT04432454 | Completed Phase 2 FDA Drug

• 1 other identifier: SMX 20-001
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 16

Brief Summary

This is an open-label, multicenter, single-arm safety study evaluating the safety and tolerability of the lasofoxifene and abemaciclib combination for the treatment of pre- and postmenopausal women with locally advanced or metastatic ER+/HER2- breast cancer who have disease progression on first and/or 2nd lines of hormonal treatment for metastatic disease and have an ESR1 mutation.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of the combination of lasofoxifene and abemaciclib as measured by number of adverse events (AEs), severity of AEs and mortality due to AEs at every scheduled visit.

  AEs will be assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.

  All subjects enrolled in the study will be treated until documented disease progression or until withdrawal for any reason. Safety and tolerability will be assessed from enrollment up to 24 months.

Secondary Outcomes (6)

• Progression free survival (PFS)

  Up to 24 months

• Clinical benefit rate (CBR)

  24 weeks or longer

• Objective response rate (ORR)

  All subjects enrolled in the study will be treated until documented disease progression or until withdrawal for any reason. ORR will be assessed up to 24 months.

• Duration of response (DoR)

  DoR will be assessed up to 24 months.

• Time to response

  Time to response will be assessed up to 24 months.

Study Arms (1)

Treatment

EXPERIMENTAL

Women who have locally advanced or metastatic ER+/HER2- breast cancer and disease progression on first and/or 2nd lines of hormonal treatment for metastatic disease and have an ESR1 mutation

Drug: Lasofoxifene and abemaciclib (VERZENIO (R)).

Interventions

Lasofoxifene and abemaciclib (VERZENIO (R)). DRUG

Lasofoxifene 5 mg given once a day orally and abemaciclib 150 mg given twice a day orally.

Treatment

Eligibility Criteria

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

You may qualify if:

• Pre- or postmenopausal.
• Postmenopausal women are defined as:
• ≥ 60 years of age with no vaginal bleeding over the prior year, or
• \< 60 years with "premature menopause" or "premature ovarian failure" manifest itself with secondary amenorrhea for at least 1 year and follicle stimulating hormone (FSH) and estradiol levels in the postmenopausal range according to institutional standards, or
• surgical menopause with bilateral oophorectomy. Note: Premenopausal women who meet all of the other entry criteria must be maintained on ovarian suppression (such as Lupron) during the study and subjects counseled to use appropriate contraception to prevent pregnancy.
• If possible, a biopsy of metastatic breast cancer tissue should be obtained to provide histological or cytological confirmation of ER+/HER2- disease as assessed by a local laboratory, according to American Society of Clinical Oncology/College of American Pathologists guidelines, using slides, paraffin blocks, or paraffin samples. If a biopsy is not possible, the ER and HER2 status from the tissue obtained at the time of the original diagnosis must confirm that the subject is ER+ and HER2-.
• Locally advanced and/or metastatic breast cancer with radiological or clinical evidence of progression on the first or 2nd lines of hormonal therapy for metastatic disease. Progression may have occurred on no more than 2 of the following endocrine treatments for metastatic breast cancer: an aromatase inhibitor (AI) and/or fulvestrant either as monotherapy or in combination with any commercially approved CDKi; and/or the combination of fulvestrant and everolimus; and/or the combination of fulvestrant and alpelisib; and/or tamoxifen; and/or the combination of exemestane/everolimus. (Note: before starting study treatment, subjects should have stopped any CDKi for at least 21 days)
• Subjects must have had no evidence of progression for at least 6 months during their first hormonal treatment for advanced breast cancer.
• At least one or more of the following ESR1 point mutations as assessed in cell-free circulating tumor DNA (ctDNA) obtained from a blood or tissue sample: Y537S, Y537C, D538G, E380Q, S463P, V534E, P535H, L536H, L536P, L536R, L536Q, or Y537N. Note: the Sponsor's blood ctDNA assay must be used but tissue sequencing (if done) may be done by a validated commercial laboratory.
• Note: A positive ESR1 mutation in tissue or ctDNA using a validated commercial assay if done prior or at the time of disease progression is acceptable to meet this entry criteria. However, blood for ctDNA must still be obtained for genomic analyses using the sponsor's ctDNA assay.
• Locally advanced or metastatic breast cancer with either measurable (according to RECIST 1.1) or non-measurable lesions.
• Subjects may have received one cytotoxic chemotherapy regimen for metastatic disease as well as those who received one cytotoxic chemotherapy regimen in the neo-adjuvant or adjuvant setting prior to entry into the trial can be enrolled but must be free of all chemotherapy acute toxicity excluding alopecia and Grade 2 peripheral neuropathy before study entry. A washout period of at least 21 days is required between last chemotherapy dose and entry into the study.
• Stable breast cancer metastasis to the brain is allowed as long as the subject has received radiotherapy and not demonstrated any evidence of brain metastasis progression for at least 3 months after the completion of radiotherapy.
• ECOG performance score of 0 or 1.
• Adequate organ function as shown by:

You may not qualify if:

• Lymphangitic carcinomatosis involving the lung.
• Visceral crisis in need of cytotoxic chemotherapy as assessed by the investigator.
• Radiotherapy within 30 days prior to entry into the study except in case of localized radiotherapy for analgesic purposes or for lytic lesions at risk of fracture, which can then be completed within 7 days prior to entry into the study. Subjects must have recovered from radiotherapy toxicities prior to entry into the study.
• Subjects with known inactivating RB1 mutations or deletions (Screening for RB1 mutation is not required for entry).
• History of long QTC syndrome or a QTC of \> 480 msec.
• History of a pulmonary embolus (PE) or deep vein thrombosis (DVT) within the last 6 months or any known thrombophilia. Subjects stable on anti-coagulants for maintenance are eligible as long as the DVT and/or PE occurred \> 6 months prior to enrollment and there is no evidence for active thrombosis. The use of low-dose ASA is permitted.
• Subjects on concomitant strong CYP3A4 inhibitors such as clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir.
• Subjects on strong and moderate CYP3A4 inducers such as amprenavir, barbiturates, carbamazepine, clotrimazole, dexamethasone, efavirenz, ethosuximide, griseofulvin, modafinil, nevirapine, oxcarbazepine, phenobarbital, phenytoin, chronic prednisone treatment, primidone, rifabutin, rifampin, rifapentine, ritonavir, topiramate.
• Any significant co-morbidity that would impact the study or the subject's safety. Since CDKi have reported the occurrence of interstitial lung disease (ILD), subjects with a history of ILD and those with severe dyspnea at rest or requiring oxygen therapy should not enter the study
• Subject has an active systemic bacterial or fungal infection (requiring intravenous \[IV\] antibiotics at the time of initiating study treatment).
• History of a positive human immunodeficiency virus (HIV) or hepatitis B virus (HBV) test. Screening is not required for enrollment.
• Subjects with hepatitis C virus (HCV) at Screening who still have a viral load. Subjects previously treated and achieved a HCV cure (no viral load) can be entered into the study
• History of malignancy within the past 5 years (excluding breast cancer), except basal cell or squamous cell carcinoma of the skin curatively treated by surgery, or early-stage cervical cancer.
• Positive serum pregnancy test (only if premenopausal).
• History of non-compliance to medical regimens.

Sponsors & Collaborators

• Sermonix Pharmaceuticals Inc.: lead

Study Sites (16)

University of Alabama at Birmingham (UAB) - Comprehensive Cancer Center

Birmingham, Alabama, 35294-3300, United States

Location

Yuma Regional Medical Center

Yuma, Arizona, 85364, United States

Location

Compassionate Cancer Care Med Group - Clinic Aid USA - Fountain Valley

Fountain Valley, California, 92708, United States

Location

St. Joseph Health

Santa Rosa, California, 95403, United States

Location

Mayo Jacksonville

Jacksonville, Florida, 32224, United States

Location

Illinois Cancer Care

Peoria, Illinois, 61704, United States

Location

Beacon Health System Memorial Regional Cancer Center

South Bend, Indiana, 46601, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

New Jersey Cancer Care, PA

Belleville, New Jersey, 07109, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

Oncology Consultants, P.A.

Houston, Texas, 77030, United States

Location

Hematology Oncology Associates of Fredericksburg

Fredericksburg, Virginia, 22408, United States

Location

Northwest Medical Specialists, PLLC (NWMS)

Tacoma, Washington, 98405, United States

Location

Related Publications (2)

• Damodaran S, O'Sullivan CC, Elkhanany A, Anderson IC, Barve M, Blau S, Cherian MA, Peguero JA, Goetz MP, Plourde PV, Portman DJ, Moore HCF. Open-label, phase II, multicenter study of lasofoxifene plus abemaciclib for treating women with metastatic ER+/HER2- breast cancer and an ESR1 mutation after disease progression on prior therapies: ELAINE 2. Ann Oncol. 2023 Dec;34(12):1131-1140. doi: 10.1016/j.annonc.2023.09.3103.

  PMID: 38072513 DERIVED

• Blau S, Peguero JA, Moore HCF, Anderson IC, Barve MA, Cherian MA, Elkhanany A, O'Sullivan CC, Moreno-Aspitia A, Plourde P, Gleich LL, Riesen K, Ezzati R, Degele M, Shulman M, Stempf SD, Sachse L, Iyer AA, Damodaran S, Cooney MM. Operational Metrics for the ELAINE 2 Study Combining a Traditional Approach With a Just-in-TIME Model. JCO Clin Cancer Inform. 2023 Jun;7:e2200164. doi: 10.1200/CCI.22.00164.

  PMID: 37352479 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Lasofoxifene; abemaciclib

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2020
• First Posted: June 16, 2020
• Study Start: September 29, 2020
• Primary Completion: January 28, 2025
• Study Completion: January 28, 2025
• Last Updated: February 13, 2025

Record last verified: 2025-02

Locations

US (16)