NEOadjuvant Abemaciclib and GIredestrant TriaL in Patients with ER-positive, HER2-negative Early Breast Cancer

NCT06259929 | Recruiting Phase 2

• 1 other identifier: GIM31-Neo-AGILE
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 8

Brief Summary

The objective of the study is to evaluate the efficacy and the safety of abemaciclib and giredestrant before surgery in participants with early stage, oestrogen receptor-positive (ER+), human epidermal receptor 2 negative (HER2-) breast cancer (BC). Primary objective: ● To evaluate the efficacy of abemaciclib and giredestrant in complete cell cycle arrest (CCCA) rate at Week 2. Secondary objectives:

• To evaluate the efficacy of abemaciclib and giredestrant in reducing the relative Ki67 expression from baseline to Week 2
• To evaluate the efficacy of abemaciclib and giredestrant in risk of recurrence (ROR) score reduction, clinical and radiological tumor response;
• To evaluate the safety of abemaciclib and giredestrant. Exploratory objectives:
• To evaluate the mechanisms of response and resistance to therapy;
• To evaluate the correlation between Ki-67% reduction and 18- Fluorothymidine (FLT) uptake reduction;
• To evaluate the pathological complete response (pCR) rate (ypT0/is, ypN0) of giredestrant plus abemaciclib

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Efficacy of abemaciclib and giredestrant in complete cell cycle arrest (CCCA) rate

  CCCA rate, defined as the proportion of patients with centrally assessed Ki67 scores ≤ 2.7% in stained biopsies

  Week 2

Secondary Outcomes (4)

• Efficacy of abemaciclib and giredestrant in reducing the relative Ki67 expression

  from baseline to Week 2 and at surgery (after the last dose of abemaciclib and giredestrant)

• Efficacy of abemaciclib and giredestrant in risk of recurrence (ROR) score change, clinical and radiological tumor response

  from baseline to Week 2 and at surgery (after the last dose of abemaciclib and giredestrant)

• Clinical and radiologic objective responses rate

  Screening, Week 2, Week 12, Week 24 then through follow-up completion (up to a year)

• Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0

  Screening, during the treatment/surgery then through follow-up completion (up to a year)

Other Outcomes (3)

• Incidence of response and resistance to therapy

  Screening, Week 2, Week 12, Week 24, during surgery (after the last dose of abemaciclib and giredestrant), until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year

• Ki-67% and 18- Fluorothymidine (FLT) correlation

  from baseline to Week 2 and at surgery (after the last dose of abemaciclib and giredestrant)

• Pathological complete response (pCR) rate (ypT0/is, ypN0) of giredestrant plus abemaciclib

  Screening, Week 2, Week 12, Week 24 then through follow-up completion (up to a year)

Study Arms (1)

Patients with ER-positive, HER2-negative Early breast cancer

EXPERIMENTAL

Abemaciclib 150 mg oral twice daily (BID) and giredestrant 30 mg oral once daily (OD) on Days 1-28.

Drug: Abemaciclib 150 MG + Giredestrant 30 MG

Interventions

Abemaciclib 150 MG + Giredestrant 30 MG DRUG

Enrolled patients will receive 6 cycles of treatment in the absence of disease progression or unacceptable toxicity for a total of 24 weeks (2 weeks of opportunity phase and 22 weeks of neoadjuvant phase) before surgery

Patients with ER-positive, HER2-negative Early breast cancer

Eligibility Criteria

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

You may qualify if:

• Female patients willing and able to give written informed consent;
• Women≥18 years of age;
• Postmenopausal women, as defined by at least one of the following criteria:
• ≥12 months of amenorrhea without an alternate medical cause plus follicle-stimulating hormone (FSH) and plasma estradiol levels within postmenopausal range by local laboratory assessment, in the absence of oral contraceptive pills, hormone replacement therapy, or gonadotropin-releasing hormone agonist or antagonist. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient;
• Documented bilateral oophorectomy (≥ 14 days prior to first treatment on Day 1 of Cycle 1 and recovery from surgery to baseline);
• Patients with cT1c (≥1.0 cm)-cT4a-c BC at presentation; a-c primary tumor must be ≥ 1.0 cm in longest diameter by ultrasound;
• Confirmed ER+ disease by local testing on primary disease specimen: tumor must be ER ≥ 10% defined by immunohistochemistry (IHC) according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines for hormone receptor testing;
• Confirmed HER2- disease by local testing on primary disease specimen: tumor must be HER2- according to ASCO/CAP 2023 guidelines for HER2 testing;
• Patients with multifocal or multicentric breast cancer with at least one tumor lesion ≥1.0 cm in the longest diameter by ultrasound (reference lesion) are also eligible if the two largest tumor lesions have been histologically confirmed in the clinical evaluation and meet pathologic criteria for ER positivity and HER2 negativity.
• No previous treatment of the disease by chemotherapy, hormone therapy, surgery or radiotherapy;
• Patients considered appropriate for endocrine therapy according to physician judgment;
• Patients with breast cancer eligible for primary surgery;
• Eastern Cooperative Oncology Group (ECOG) performance status≤1;
• Adequate bone marrow and coagulation and adequate organ function defined as follows:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L;

You may not qualify if:

• Patients with bilateral invasive BC;
• Patients with metastatic BC (local spread to axillary lymph nodes is permitted (cN1\_cN2a);
• Patients with inflammatory BC;
• Non post-menopausal patients;
• Patients having received previous systemic or local treatment for BC, in particular history of any prior treatment with aromatase inhibitors (AIs), tamoxifen, selective estrogen receptor down regulator, or cyclin-dependent kinase 4 and 6 inhibitors;
• Participants who have active cardiac disease or history of cardiac dysfunction, including any of the following:
• History (within 2 years of screening) or presence of idiopathic bradycardia or resting heart rate \< 50 beats per minute at screening
• History of angina pectoris or symptomatic coronary heart disease within 12 months prior to randomization
• History of documented congestive heart failure (New York Heart Association Class III or IV) or cardiomyopathy
• QT interval corrected through use of Fridericia's formula \>470 ms for women \> 450 ms for men based on mean value of triplicate ECGs, history of long or short QT syndrome, Brugada syndrome or known history of corrected QT interval prolongation, or torsades de pointes
• Participants with pacemakers to treat more severe heart blocks and other arrhythmias are permitted.
• Patients with history of well-controlled atrial fibrillation are eligible.
• History (within 12 months) or presence of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as significant structural heart disease (e.g., severe left ventricular systolic dysfunction, restrictive cardiomyopathy, hypertrophic cardiomyopathy, infiltrative cardiomyopathy, moderate-to-severe valve disease), or family history of long QT syndrome) o Clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia) should be corrected prior to enrollment.
• Patients with known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including hepatitis;
• Patients with history of invasive BC, ductal carcinoma in situ or lobular carcinoma in situ and other malignancy within 5 years prior to screening;

Sponsors & Collaborators

• Fondazione Oncotech: lead

Study Sites (8)

Humanitas Istituto Clinico Catanese

Catania, Catania, 95045, Italy

NOT YET RECRUITING

IRCCS Ospedale Policlinico San Martino

Genova, Genova, 16132, Italy

NOT YET RECRUITING

AOU Federico II

Napoli, Napoli, 80131, Italy

NOT YET RECRUITING

Istituto Nazionale Tumori "G. Pascale"

Napoli, Napoli, 80131, Italy

RECRUITING

Istituto Oncologico Veneto IRCCS

Padua, Padova, 35128, Italy

NOT YET RECRUITING

IRCCS Centro di Riferimento Oncologico (CRO)

Aviano, PN, 33081, Italy

NOT YET RECRUITING

Fondazione Universitaria Policlinico Gemelli IRCCS

Roma, Roma, 00168, Italy

NOT YET RECRUITING

Ospedale Fatebenefratelli - Isola Tiberina

Roma, Roma, 00186, Italy

NOT YET RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

abemaciclib; giredestrant

Condition Hierarchy (Ancestors)

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

Study Officials

• Michelino De Laurentiis, MD

  National Cancer Institute, Naples

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michelino De Laurentiis, MD

CONTACT

08117770442; m.delaurentiis@istitutotumori.na.it

Claudia Von Arx, MD

CONTACT

0815903565; Claudia.vonarx@istitutotumori.na.it

Study Design

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

Study Record Dates

• First Submitted: January 30, 2024
• First Posted: February 14, 2024
• Study Start: January 27, 2025
• Primary Completion: April 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: February 18, 2025

Record last verified: 2025-02

Locations

IT (8)