MEN1611 With Trastuzumab (+/- Fulvestrant) in Metastatic Breast Cancer (B-PRECISE-01)

Open-label, Multicentre, Phase Ib Dose-escalation Study of MEN1611, a PI3K Inhibitor Combined With Trastuzumab With or Without Fulvestrant, in Subjects With PIK3CA Mutated HER2 Positive Locally Recurrent Unresectable (Advanced) or Metastatic (a/m) Breast Cancer Progressed to Anti-HER2 Based Therapy

The main purpose of this open-label, dose-escalation, phase Ib study is to identify the appropriate dose of MEN1611 to be used in combination with Trastuzumab with/without Fulvestrant for the treatment of advanced or metastatic HER2-positive breast cancer

Study Overview

• Status: Completed
• Conditions: Advanced or Metastatic Breast Cancer
• Intervention / Treatment: Drug: MEN1611; Drug: Trastuzumab; Drug: Fulvestrant

Detailed Description

This Phase Ib study will investigate the safety and anti-tumor activity of daily oral doses MEN1611 in combination with Trastuzumab with/without Fulvestrant in female and male patients affected by advanced or metastatic HER2-positive breast cancer. Fulvestrant will be added to the post-menopausal patients with hormone-sensitive disease.

MEN1611 is an investigational drug which blocks a protein called PI3K (phosphoinositide 3-kinase) involved in cancer cells growth. The Maximum Tolerated Dose (MTD) of MEN1611 given as single agent was assessed in a phase I trial in patients with advanced solid tumors.

This Phase IB will start with a dose escalation part (Step 1) to identify the MTD of MEN1611 given in combination with Trastuzumab with/without Fulvestrant.

The study will continue with a cohort expansion (Step 2) to investigate the anti-tumor activity of the selected MEN1611 dose level considered to be tolerable by a Safety Review Committee.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • Institut Jules Bordet
  • Brussels, Belgium
    • Cliniques Universitaires Saint-luc
  • Leuven, Belgium
    • UZ Leuven
• France
  • Dijon, France
    • Centre Georges Francois Leclerc
  • Lille Cedex, France
    • Centre Oscar Lambret
  • Montferrier Sur Lez, France
    • Institut Regional du Cancer de Montpellier
  • Saint-Herblain, France
    • ICO - Site René Gauducheau
  • Toulouse, France
    • Institut Claudius Regaud Oncopole
  • Villejuif cedex, France
    • Institut Gustave Roussy
• Italy
  • Catanzaro, Italy
    • Azienda Ospedaliero Universitaria Mater Domini
  • Milan, Italy
    • Ospedale San Raffaele
  • Milan, Italy
    • Istituto Clinico Humanitas
  • Milan, Italy
    • Istituto Europeo di Oncologia (IEO)
• Spain
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain
    • Hospital Clinic i Provincial de Barcelona
  • Madrid, Spain
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain
    • Centro Integral Oncologico Clara Campal
  • Madrid, Spain
    • Start Madrid Fundacion Jimenez Diaz
  • Málaga, Spain
    • Hospital Clínico Universitario Virgen de la Victoria
  • Sevilla, Spain
    • Hospital Universitario Virgen del Rocio
• United Kingdom
  • Cardiff, United Kingdom
    • Velindre Cancer Centre
  • London, United Kingdom
    • University College London Hospitals
  • London, United Kingdom
    • Sarah Cannon Research Institute UK
  • Manchester, United Kingdom
    • The Christie
• United States
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital Inc.
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Detroit Clinical Research Center
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Washington University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Main Inclusion Criteria:

• Histologically confirmed invasive adenocarcinoma of the breast
• Known HER2+ breast cancer
• Advanced or metastatic breast cancer harbouring PIK3CA mutation on tissue sample
• > 2 lines of anti-HER2 based regimens with at least 1 regimen with trastuzumab
• Radiological documented evidence of progressive disease
• Life expectancy ≥ 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

Main Exclusion Criteria:

• Previous treatment with PI3K inhibitors
• Brain metastases untreated, unless treated > 4 weeks and only if clinically stable and not receiving corticosteroids
• History of clinically significant bowel disease
• ≥ grade 2 diarrhoea
• History of significant, uncontrolled, or active cardiovascular disease
• Any serious and/or unstable pre-existing psychiatric or neurologic illness or other conditions that could interfere with patient's safety
• Not controlled diabetes mellitus (glycated haemoglobin [HbA1c] >7%) and fasting plasma glucose >126 mg/dL
• Concurrent chronic treatment with steroids, as immunosuppressant, or another immunosuppressive agent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MEN1611; MEN1611 + Trastuzumab +/- Fulvestrant	Drug: MEN1611; MEN1611 oral dose administered twice daily for a continuous 28-day cycle; Drug: Trastuzumab; Trastuzumab solution for infusion administered weekly via IV; Drug: Fulvestrant; Fulvestrant solution for injection administered monthly via IM (only for HR-positive postmenopausal women)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MTD of MEN1611 in Combination With Trastuzumab ± Fulvestrant	MTD was defined as the highest dose level at which no more than 1 participant experienced a DLT during the 28-day DLT assessment window.	Up to 28 Days
Number of Participants With DLTs of MEN1611 in Combination With Trastuzumab ± Fulvestrant	DLT was defined as the occurrence of any of the protocol defined adverse drug reactions (ADRs) related to the combination regimens or to MEN1611 alone and unrelated to the participants' underlying disease or concomitant medication occurring during 28 days after the first MEN1611 administration.	Up to 28 days
RP2D of MEN1611 in Combination With Trastuzumab ± Fulvestrant	RP2D was defined as the highest dose level in milligrams (mg) at which no more than 1 participant experienced a DLT during the DLT assessment window (28days), or the maximum dose judged to be tolerable.	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Overall Response (BOR) of MEN1611 in Combination With Trastuzumab ± Fulvestrant	BOR was defined as percentage of participants who had a best overall response to therapy of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) and was defined according to Response Evaluation Criteria in Solid Tumors version 1.1 assessment locally performed using computed tomography scans or magnetic resonance imaging of the chest and abdomen (including pelvis and adrenal glands).	Up to 3 years
Objective Response Rate (ORR) of MEN1611 in Combination With Trastuzumab ± Fulvestrant	ORR was calculated as the sum of the Best Overall Response (BOR) of complete response (CR) and partial response (PR) rates. ORR was defined according to Response Evaluation Criteria in Solid Tumors version 1.1assessment performed using computed tomography scans or magnetic resonance imaging of the chest and abdomen (including pelvis and adrenal glands).	Up to 3 years
Disease Control Rate (DCR) of MEN1611 in Combination With Trastuzumab ± Fulvestrant	DCR was defined as percentage of participants whose disease shrank or remained stable over a certain time period and was calculated as the sum of the best overall response (BOR) rates of CR, PR and Stable Disease (SD) rates.	Up to 3 years
Duration of Response (DOR) of MEN1611 in Combination With Trastuzumab ± Fulvestrant	DOR was defined as time from first occurrence of a BOR of PR, CR or SD as locally assessed, until the disease has been shown to progress following treatment. Participants with a previous response who did not show a relapse or die without recording a relapse were censored at their last available relapse-free tumour assessment date. Participants with only one tumour assessment after baseline showing progressive disease (PD) were not included in the calculation.	Up to 3 years
Progression-free Survival (PFS) of MEN1611 in Combination With Trastuzumab ± Fulvestrant	PFS was defined as the number of days between the first study treatment administration to the date of first documented disease progression as per local assessment, relapse or death from any cause. Responding participants and participants who were lost to follow-up were censored at their last tumour assessment date.	Up to 3 years
Overall Survival (OS) of MEN1611 in Combination With Trastuzumab ± Fulvestrant	OS was defined as the number of days between the first study treatment administration and death from any cause. Participants still alive who had withdrawn from the study were censored using the latest among end of study and follow-up dates. Drop-out participants were considered censored and the last available date in which the participant was known to be alive were used for calculation.	Up to 3 years

Collaborators and Investigators

• Sponsor: Menarini Group
• Investigators: Study Chair: Martine Piccart, MD PhD, Institute Jules Bordet - Boulevard De Waterloo 125 - B-1000 Brussels, Belgium

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2018
• Primary Completion (Actual): February 23, 2024
• Study Completion (Actual): February 23, 2024

Study Registration Dates

• First Submitted: December 5, 2018
• First Submitted That Met QC Criteria: December 5, 2018
• First Posted (Actual): December 6, 2018

Study Record Updates

• Last Update Posted (Actual): June 26, 2025
• Last Update Submitted That Met QC Criteria: June 9, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Advanced Breast Cancer; Metastatic Breast Cancer; HER2-positive; PI3K inhibitor
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Estrogen Receptor Antagonists; Estrogen Antagonists; Trastuzumab; Fulvestrant
• Other Study ID Numbers: MEN1611-01; 2017-004631-36 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No