PIK3CA/PTEN-altered Advanced Breast Cancer Treated With MEN1611 Monotherapy or in Combination With Eribulin

NCT05810870 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: MEDOPP4372022-001398-30
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 13

Brief Summary

The multicenter, two-cohort, non-comparative, open-label, phase II clinical trial SABINA aims to analyze the safety and efficacy of MEN1611 in monotherapy and in combination with eribulin, a non-taxane chemotherapy agent, in Hormone Receptor (HR)-known/Human Epidermial Growth Factor Receptor 2 (HER2)-negative, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)/ Phosphatase and Tensin Homolog (PTEN)-altered, unresectable locally advanced or metastatic metaplastic breast carcinoma (MpBC) patients. A run-in phase for safety and tolerability of MEN1611 in combination with standard doses of eribulin will be conducted as an initial step of the cohort A. This first step aims at evaluating the dosing schedule of MEN1611, by analyzing the toxicity profile of the combined regimen. With the background of the first-in-human study (PA-001EU), the safe dose of MEN1611 has been established as 48 mg orally BID (two intakes of 3 capsules of 16 mg each, for a total daily dose of 96 mg MEN1611 free-base).

Conditions

Metastatic Breast Cancer; Breast Cancer; Advanced Breast Cancer

Keywords

Breast cancer; MEN1611; Eribulin

Outcome Measures

Primary Outcomes (1)

• To assess the efficacy of MEN1611 in combination with eribulin as determined by the clinical benefit rate (CBR).

  CBR, defined as the percentage of patients who experience a complete response (CR), partial response (PR) or stable disease (SD) for at least 12 weeks after the start of MEN1611 in combination with eribulin treatment, as determined locally by the investigator per RECIST v1.1 criteria.

  Baseline up to at least 12 weeks

Secondary Outcomes (6)

• To determine the efficacy of MEN1611 in combination with eribulin defined as ORR of patients.

  Baseline up to 24 months

• To determine the efficacy of MEN1611 in combination with eribulin defined as Time To Response (TTR).

  Baseline up to 24 months

• To determine the efficacy of MEN1611 in combination with eribulin defined as Duration of Response (DoR) of patients.

  Baseline up to 24 months

• To determine the efficacy of MEN1611 in combination with eribulin defined as Progression-Free Survival (PFS).

  Baseline up to 24 months

• To determine the efficacy of MEN1611 in combination with eribulin defined as Overall Survival (OS).

  Baseline up to 24 months

Study Arms (1)

Cohort A

EXPERIMENTAL

MEN1611 orally (PO) 48 mg twice daily (BID) (2 intakes of 3x16 mg capsules, for a total daily dose of 96 mg MEN1611 free-base) during each 21-day cycle combined with eribulin mesylate 1.4 mg/m2 (equivalent to eribulin 1.23 mg/m2 when expressed as a free base) administered intravenously (IV) over 2 to 5 minutes on days 1 and 8 of every 21-day cycle (CXD1 and CXD8). A run-in phase for safety and tolerability of MEN1611 in combination with eribulin will be conducted after the first 2 cycles on the first 3 patients. Upon Steering Committee agreement the cohort A will be expanded up to N=14 (11 additional patients). Patients will receive treatment until disease progression, unacceptable toxicity, death, discontinuation from the study treatment for any other reason, withdrawal of consent, or study termination.

Drug: MEN1611; Drug: Eribulin

Interventions

MEN1611 DRUG

MEN1611 is a potent, orally bioavailable selective inhibitor of the class I phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) with a novel structure which exhibits a strong inhibitory activity especially against the PI3K catalytic subunit alpha (PIK3CA), with potential antineoplastic activity. PI3K alpha inhibitor MEN1611 selectively binds to and inhibits PIK3CA and its mutated forms in the PI3K/Akt (protein kinase B)/mammalian target of rapamycin (mTOR) pathway.

Cohort A

Eribulin DRUG

Eribulin mesylate (eribulin), a non-taxane inhibitor of microtubule dynamics of the halichondrin class of antineoplastics, suppresses microtubule growth and sequesters tubulin into nonfunctional aggregates, preventing mitotic spindle formation with subsequent G2-M stop and apoptosis.

Also known as: HALAVEN, Eribulin mesylate

Cohort A

Eligibility Criteria

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

You may qualify if:

• PRE-SCREENING PHASE
• The following criteria must be met to be eligible to entry into the pre-screening:
• Patient must be able to sign written pre-screening form prior to any molecular determination during the pre-screening phase.
• Being male or female aged ≥ 18 years.
• \- Histologically confirmed metaplastic or non-metaplastic TNBC as per local assessment.
• \- Histologically confirmed HR-positive/HER2-negative metaplastic breast cancer
• Known HR status according to the updated American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) 2020 guidelines and HER2-negative breast cancer (BC) as per ASCO/CAP 2018 criteria based on local testing on the most recently analyzed biopsy.
• Prior treatment with at least one, but no more than four, prior lines of systemic therapy for advanced disease. Earlier adjuvant or neoadjuvant therapy for more limited disease will be considered as one of the required prior regimens if the development of unresectable locally advanced metastatic disease occurred within a 6-month period after completion of chemotherapy.
• No prior treatment with a PI3K/AKT/mTOR inhibitors, nor with eribulin.
• Patient must consent to give a tumor sample or/and a blood sample for testing of the prior mentioned alterations (or if needed and deemed safe by the Investigator, able to provide a fresh tumor sample).
• Unknown PIK3CA mutational and/or PTEN loss status.
• SCREENING PHASE
• Patient must be able to sign written main informed consent form (ICF) prior to participation in any Study-related activities.
• Eastern Cooperative Oncology Group (ECOG) performance status must be 0 or 1 which the Investigator believes is stable at the time of screening.
• Life expectancy greater or equal to 12 weeks.

You may not qualify if:

• Any patient meeting ANY of the following criteria will be excluded from the Study:
• Current participation in another therapeutic clinical trial.
• Extra-cranial radiotherapy or limited-field palliative radiotherapy within 7 days prior to Study enrolment, or patients who have not recovered from radiotherapy-related toxicities to baseline or grade ≤ 1 and/or from whom ≥ 25% of the bone marrow has been previously irradiated.
• Major surgery (defined as requiring general anesthesia) or significant traumatic injury within 21 days of start of Study drug, or patients who have not recovered from the side effects of any major surgery.
• Patient with a concurrent malignancy or malignancy within 5 years of Study enrollment except for carcinoma in situ of the cervix, non-melanoma skin carcinoma, or stage I uterine cancer.
• Note: For other cancers considered to have a low risk of recurrence, discussion with the Medical Monitor is required.
• Treatment with approved chemotherapy/immunotherapy/ targeted agents within 21 days prior to initiation of Study, or treatment with an investigational cancer therapy for 21 days or 5 half-lives (whichever is longer) prior to initiation of any Study treatment.
• Patient with cerebrovascular accident or transient ischemic attack within 6 months prior to the start of any Study treatment.
• Congenital long QT syndrome or screening QT interval corrected using Fridericia's formula (QTcF) \> 480 milliseconds.
• Patient with an active cardiac disease or a history of cardiac dysfunction or conduction abnormalities including any of the following:
• Unstable angina pectoris or documented myocardial infarction within 6 months prior to Study entry.
• Symptomatic pericarditis.
• Documented congestive heart failure (New York Heart Association functional classification III- IV).
• Left ventricular ejection fraction (LVEF) \< 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO).
• Ventricular arrhythmias except for benign premature ventricular contractions.

Sponsors & Collaborators

• MedSIR: lead
• Menarini Group: collaborator

Study Sites (13)

Hospital Universitario Clínico San Cecilio de Granada

Granada, Andalusia, 18016, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, Andalusia, 41013, Spain

Location

Onkologikoa

Donostia / San Sebastian, Basque Country, 20014, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Centro Oncológico de Galicia

A Coruña, Galicia, 15009, Spain

Location

Hospital Universitario de Torrejón

Torrejón de Ardoz, Madrid, 28850, Spain

Location

CHUVI - Complejo Hospitalario Universitario de Vigo

Vigo, Pontevedra, 36312, Spain

Location

Hospital Clínic i Provincial de Barcelona

Barcelona, 08036, Spain

Location

Institut Català d' Oncologia L'Hospitalet (ICO)

Barcelona, 08907, Spain

Location

Hospital Universitari Vall D'Hebron

Barcelona, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Beata María Ana

Madrid, Spain

Location

Instituto Valenciano de Oncología (IVO)

Valencia, 46009, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

eribulin

Condition Hierarchy (Ancestors)

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

Study Officials

• José Pérez, MD

  Institute of Breast Cancer, Quirón Group, Barcelona (Spain)

  PRINCIPAL INVESTIGATOR

• Antonio Llombart-Cussac, MD

  Arnau de Vilanova Hospital, Valencia (Spain)

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Multicenter, single-cohort, non-comparative, open-label, phase II clinical trial.

Study Record Dates

• First Submitted: March 30, 2023
• First Posted: April 12, 2023
• Study Start: May 24, 2023
• Primary Completion: April 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: March 10, 2026

Record last verified: 2025-09

Locations

ES (13)