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

NCT03767335 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: MEN1611-012017-004631-36
• Study Type: interventional
• Target: 62
• Locations: 6 countries
• Sites: 27

Brief Summary

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

Conditions

Advanced or Metastatic Breast Cancer

Keywords

Advanced Breast Cancer; Metastatic Breast Cancer; PI3K inhibitor; HER2-positive

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (6)

• Best Overall Response (BOR) of MEN1611 in Combination With Trastuzumab ± Fulvestrant

  Up to 3 years

• Objective Response Rate (ORR) of MEN1611 in Combination With Trastuzumab ± Fulvestrant

  Up to 3 years

• Disease Control Rate (DCR) of MEN1611 in Combination With Trastuzumab ± Fulvestrant

  Up to 3 years

• Duration of Response (DOR) of MEN1611 in Combination With Trastuzumab ± Fulvestrant

  Up to 3 years

• Progression-free Survival (PFS) of MEN1611 in Combination With Trastuzumab ± Fulvestrant

  Up to 3 years

Study Arms (1)

MEN1611

EXPERIMENTAL

MEN1611 + Trastuzumab +/- Fulvestrant

Drug: MEN1611; Drug: Trastuzumab; Drug: Fulvestrant

Interventions

MEN1611 DRUG

MEN1611 oral dose administered twice daily for a continuous 28-day cycle

MEN1611

Trastuzumab DRUG

Trastuzumab solution for infusion administered weekly via IV

MEN1611

Fulvestrant DRUG

Fulvestrant solution for injection administered monthly via IM (only for HR-positive postmenopausal women)

MEN1611

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Menarini Group: lead

Study Sites (27)

Holy Cross Hospital Inc.

Fort Lauderdale, Florida, 33308, United States

Location

Detroit Clinical Research Center

Farmington Hills, Michigan, 48334, United States

Location

Washington University

St Louis, Missouri, 63130, United States

Location

Cliniques Universitaires Saint-Luc

Brussels, Belgium

Location

Institut Jules Bordet

Brussels, Belgium

Location

UZ Leuven

Leuven, Belgium

Location

Centre Georges François Leclerc

Dijon, France

Location

Centre Oscar Lambret

Lille, France

Location

Institut Régional du Cancer de Montpellier

Montferrier-sur-Lez, France

Location

ICO - Site René Gauducheau

Saint-Herblain, France

Location

Institut Claudius Regaud Oncopole

Toulouse, France

Location

Institut Gustave Roussy

Villejuif, France

Location

Azienda Ospedaliero Universitaria Mater Domini

Catanzaro, Italy

Location

Istituto Clinico Humanitas

Milan, Italy

Location

Istituto Europeo di Oncologia (IEO)

Milan, Italy

Location

Ospedale San Raffaele

Milan, Italy

Location

Hospital Clínic i Provincial de Barcelona

Barcelona, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

Centro Integral Oncologico Clara Campal

Madrid, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, Spain

Location

START Madrid Fundacion Jimenez Diaz

Madrid, Spain

Location

Hospital Clínico Universitario Virgen de la Victoria

Málaga, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, Spain

Location

Velindre Cancer Centre

Cardiff, United Kingdom

Location

Sarah Cannon Research Institute UK

London, United Kingdom

Location

University College London Hospitals

London, United Kingdom

Location

The Christie

Manchester, United Kingdom

Location

Related Publications (1)

• Fiascarelli A, Merlino G, Capano S, Talucci S, Bisignano D, Bressan A, Bellarosa D, Carrisi C, Paoli A, Bigioni M, Tunici P, Irrissuto C, Salerno M, Arribas J, de Stanchina E, Scaltriti M, Binaschi M. Antitumor activity of the PI3K delta-sparing inhibitor MEN1611 in PIK3CA mutated, trastuzumab-resistant HER2 + breast cancer. Breast Cancer Res Treat. 2023 May;199(1):13-23. doi: 10.1007/s10549-023-06895-2. Epub 2023 Mar 13.

  PMID: 36913051 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; Fulvestrant

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Clinical Sciences
• Organization: Menarini Ricerche S.p.A.

martine.piccart@bordet.be

+39 05556809990

Study Officials

• Martine Piccart, MD PhD

  Institute Jules Bordet - Boulevard De Waterloo 125 - B-1000 Brussels, Belgium

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Step 1 Dose escalation / Step 2 Cohort expansion in two selected breast cancer sub-populations

Study Record Dates

• First Submitted: December 5, 2018
• First Posted: December 6, 2018
• Study Start: November 13, 2018
• Primary Completion: February 23, 2024
• Study Completion: February 23, 2024
• Last Updated: June 26, 2025
• Results First Posted: June 26, 2025

Record last verified: 2025-04

Locations

BE (3); IT (4); ES (7); GB (4); FR (6); US (3)