Efficacy & Safety Evaluation of Enobosarm in Combo With Abemaciclib in Treatment of ER+HER2- Metastatic Breast Cancer

NCT05065411 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: V2000701
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 30

Brief Summary

STAGE 1: To determine the safety of enobosarm 9 milligram (mg) once daily (QD) used in combination with a CDK 4/6 inhibitor \[Verzenio® (abemaciclib) tablets, for oral use, 150 mg twice daily (BID)\]. STAGE 2: To demonstrate the efficacy and safety of enobosarm 9 mg QD in combination with abemaciclib 150 mg BID (Enobosarm Combination Group) versus Estrogen Blocking Agent (Control Treatment Group) in the treatment of estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-), androgen receptor positive (AR+) with a AR% nuclei staining ≥40% metastatic breast cancer that have previously experienced disease progression on an estrogen blocking agent plus (palbociclib) as measured by progression free survival (PFS) according to RECIST 1.1 criteria.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Primary endpoint for the study is the median progression free survival (PFS) in the Enobosarm Combination Group compared to the Control Treatment Group in patients with AR% nuclei staining ≥40%. Progression will be defined based on RECIST 1.1 criteria

  STAGE 1: To determine the safety of enobosarm 9 mg once daily (QD) used in combination with abemaciclib tablets, for oral use, 150 mg twice daily (BID)\]. STAGE 2: To demonstrate the efficacy of enobosarm in combination with abemaciclib (Enobosarm Combination Group) versus an estrogen blocking agent, (non-steroidal AI, steroidal AI (exemestane with or without everolimus) or fulvestrant Control Treatment Group) in the treatment of AR+ER+HER2 (AR% nuclei staining ≥40%) metastatic breast cancer as measured by PFS according to RECIST 1.1.

  Day 1 to Day 300

Secondary Outcomes (1)

• Objective Response Rate (ORR), proportion of subjects with a best tumor response of ORR (partial response [PR] or complete response [CR]) on study

  Day 1 to Day 300

Study Arms (2)

Enobosarm Combination Group

EXPERIMENTAL

Enobosarm Combination Group will receive enobosarm 9 mg each day by mouth (QD), and abemaciclib will administered by mouth at a dose of 150 mg BID. Stage 2 Subjects in the Enobosarm Combination Group will receive enobosarm 9 mg QD each day by mouth and abemaciclib 150 mg BID by mouth until disease progression is observed and confirmed by BICR.

Drug: Enobosarm & Abemaciclib Combo

Control Treatment Group

ACTIVE COMPARATOR

Control Treatment Group will receive a non-steroidal AI, a non-steroidal or steroidal (exemestane with or without everolimus), AI OR fulvestrant approved for the treatment of metastatic breast cancer and is part of the standard of care at the clinical study site until disease progression is observed and confirmed by BICR. The decision of which comparator treatment will be used will be made prior to randomization.

Drug: non-steroidal AI, or steroidal AI (exemestane with or without everolimus) or Fulvestrant

Interventions

Enobosarm & Abemaciclib Combo DRUG

Subjects will receive a combo of Enobosarm \& Abemaciclib

Also known as: VERU-024, Verzenio

Enobosarm Combination Group

non-steroidal AI, or steroidal AI (exemestane with or without everolimus) or Fulvestrant DRUG

Non-steroidal AI, a steroidal AI (exemestane with or without everolimus), OR fulvestrant

Also known as: exemestane, fulvestrant, exemestane plus everolimus

Control Treatment Group

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects accepted for this study must:
• Provide informed consent
• Be able to communicate effectively with the study personnel
• Aged ≥18 years
• For Female Subjects
• Menopausal status
• Be postmenopausal as defined by the National Comprehensive Cancer Network as either: Age ≥55 years and one year or more of amenorrhea Age \<55 years and one year or more of amenorrhea, with an estradiol assay \<20 pg/mL Age \<55 years and surgical menopause with bilateral oophorectomy
• Be premenopausal or perimenopausal with a negative serum pregnancy test.
• If subject is of child bearing potential, the subject must agree to use acceptable methods of contraception:
• If female study participant could become pregnant, use acceptable methods of contraception from the time of the first administration of study medication until 6 months following administration of the last dose of study medication. Acceptable methods of contraception are as follows: Condom with spermicidal foam/gel/film/cream/suppository \[i.e., barrier method of contraception\], surgical sterilization of male partner (vasectomy with documentation of azoospermia) and a barrier method {condom used with spermicidal foam/gel/film/cream/suppository},
• If female study participant has undergone documented tubal ligation (female sterilization), a barrier method (condom used with spermicidal foam/gel/film/cream/suppository) should also be used
• If female study participant has undergone documented placement of an intrauterine device (IUD) or intrauterine system (IUS), a barrier method (condom with spermicidal foam/gel/film/cream/suppository) should also be used
• For Male Subjects
• Subject must agree to use acceptable methods of contraception:
• If the study subject's partner could become pregnant, use acceptable methods of contraception from the time of the first administration of study medication until 6 months following administration of the last dose of study medication. Acceptable methods of contraception are as follows: Condom with spermicidal foam/gel/film/cream/suppository \[i.e., barrier method of contraception\], surgical sterilization (vasectomy with documentation of azoospermia) and a barrier method {condom used with spermicidal foam/gel/film/cream/suppository}, the female partner uses oral contraceptives (combination estrogen/progesterone pills), injectable progesterone or subdermal implants and a barrier method (condom used with spermicidal foam/gel/film/cream/suppository)

You may not qualify if:

• Known hypersensitivity or allergy to enobosarm or abemaciclib
• Patients with a biliary catheter
• Creatinine clearance \< 30 milliliter per minute (mL/min) as measured using the Cockcoft Gault formula (patients with mild and moderate renal failure are not excluded from participation in this study)
• Previously received \>1 course of systemic chemotherapy (not including immunotherapies or targeted therapies) for the treatment of metastatic breast cancer.
• NOTE: Subjects may have received 1 course of chemotherapy in the adjuvant or neoadjuvant setting would not count as a line of therapy.
• Subjects with radiographic evidence of central nervous system (CNS) metastases as assessed by CT or MRI that are not well-controlled (symptomatic or requiring control with continuous corticosteroid therapy \[e.g., dexamethasone\]) NOTE: Subjects with CNS metastases are permitted to participate in the study if the CNS metastases are medically well-controlled and stable for at least 30 days after receiving local therapy (irradiation, surgery, etc.)
• The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \<30ml/min\], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
• Treatment with any investigational product within \< 4 half-lives for each individual investigational product OR within 30 days prior to randomization
• Major surgery within 30 days prior to randomization
• Testosterone, methyltestosterone, oxandrolone (Oxandrin®), oxymetholone, danazol, fluoxymesterone (Halotestin®), testosterone-like agents (such as dehydroepiandrosterone, androstenedione, and other androgenic compounds, including herbals), or antiandrogens (flutamide, bicalutamide, abiraterone, enzalutamide, apalutamide, or darolutamide). Previous therapy with testosterone and testosterone-like agents is acceptable with a 30-day washout (if previous testosterone therapy was long term depot within the past 6 months, the site should contact the Medical Monitor) or any other androgenic agent.
• Treatment with any of the following hormone therapies for metastatic breast cancer. Prior use in the adjuvant or neoadjuvant setting is allowed if the treatment is discontinued greater than 30 days prior to randomization
• Estrogens
• Megestrol acetate
• Testosterone
• All other concurrent anticancer treatments (including, but not limited to, all SERMs, estrogen blocking agents unless randomized to Control Treatment Group, and CDK 4/6 inhibitors unless randomized to the abemaciclib in Enobosarm Combination Group)

Sponsors & Collaborators

• Veru Inc.: lead

Study Sites (30)

Ironwood Cancer & Research Centers

Chandler, Arizona, 85224, United States

Location

Banner MDACC

Gilbert, Arizona, 85234, United States

Location

Arizona Oncology Associates, PC-HOPE

Tucson, Arizona, 85711, United States

Location

Los Angeles Cancer Network One Oncology

Los Angeles, California, 90017, United States

Location

UCLA Parkside Cancer Center

Los Angeles, California, 90095, United States

Location

Sharp Center for Research

San Diego, California, 92123, United States

Location

Sansum Clinic, CA

Santa Barbara, California, 93105, United States

Location

Innovative Clinical Research Institute

Whittier, California, 90603, United States

Location

Med OncologyHematology Consultants, PA Newark

Newark, Delaware, 19713-7007, United States

Location

Lakes Research

Miami Lakes, Florida, 33014, United States

Location

Maryland Oncology Hematology, P.A.

Annapolis, Maryland, 21401, United States

Location

Baystate Regional Cancer Program - D'Amour Center for Cancer Care

Springfield, Massachusetts, 01199-1005, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39213, United States

Location

Washington University St. Louis

St Louis, Missouri, 63110, United States

Location

Renown Health

Reno, Nevada, 89502, United States

Location

Summit Medical Group, Florham Park Campus

Florham Park, New Jersey, 07932-1049, United States

Location

The New York Hospital

Westbury, New York, 11590, United States

Location

The Lindner Center for Research and Education at the Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

Toledo Clinic Cancer Centers - Main Office

Toledo, Ohio, 43623, United States

Location

UPMC Magee-Women's Hospital

Pittsburgh, Pennsylvania, 15219, United States

Location

Texas Oncology, PA

Dallas, Texas, 75246, United States

Location

Texas Oncology, PA

Denton, Texas, 76201, United States

Location

Texas Oncology, P.A.

El Paso, Texas, 79902, United States

Location

Texas Oncology, P.A.

Flower Mound, Texas, 75028, United States

Location

UT MD Anderson CC

Houston, Texas, 77030, United States

Location

Texas Oncology, P.A.

San Antonio, Texas, 78240, United States

Location

Texas Oncology, P.A.

Tyler, Texas, 75702, United States

Location

Virginia Oncology Assoc

Norfolk, Virginia, 23502, United States

Location

University of Washington Seattle Cancer Center Alliance (SCCA)

Seattle, Washington, 98109-1023, United States

Location

Cancer Care Northwest

Spokane, Washington, 99216, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ostarine; abemaciclib; exemestane; Everolimus; Fulvestrant

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; 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

• Barnette

  Veru Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Only the central radiologist readers will be blinded to treatment assignments
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open Label two treatment arm

Study Record Dates

• First Submitted: September 21, 2021
• First Posted: October 4, 2021
• Study Start: April 11, 2022
• Primary Completion: October 19, 2023
• Study Completion: January 9, 2024
• Last Updated: February 26, 2024

Record last verified: 2024-02

Locations

US (30)