Ipatasertib + Pertuzumab +Trastuzumab in Advanced HER2+ PI3KCA-mutant Breast Cancer Patients

NCT04253561 | Completed Phase 1 DMC

• 2 other identifiers: SOLTI-15072019-001526-94
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 10

Brief Summary

This is an open label, single arm, multicenter, phase Ib study to evaluate the safety and clinical activity of the combination of ipatasertib, trastuzumab and pertuzumab in patients with unresectable locally advanced or metastatic HER2-positive breast cancer with tumors harboring PIK3CA mutations, candidates to receive maintenance HP after first line treatment for metastatic disease with a taxane plus HP

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• To define the Recommended Phase 2 Dose (RP2D) of ipatasertib when used in combination with HP (+/- ET)

  The RP2D will be the dose level of ipatasertib at which no more than 1 subject of the study experiences a Dose Limiting Toxicity (DLT) defined by the protocol study.

  From baseline to the end of cycle 1, up to 28 days

Secondary Outcomes (6)

• To evaluate the safety of the combination of ipatasertib with HP (+/- endocrine therapy [ET]).

  Toxicities will be assessed during the whole treatment period (from baseline until lasts until 6 months after a patients' final treatment which is defined as the end of the Treatment Phase of the study).

• To evaluate the tolerability of the combination of ipatasertib with HP (+/- endocrine therapy [ET]).

  Toxicities will be assessed during the whole treatment period (from baseline until lasts until 6 months after a patients' final treatment which is defined as the end of the Treatment Phase of the study).

• Objective Response Rate (ORR) of the combination of ipatasertib with HP (+/- ET) as maintenance therapy after first line treatment for HER2-positive metastatic BC with a taxane plus HP.

  From date of randomization to disease progression, death, unacceptable toxicity, consent withdrawal or study termination, whichever came first, assessed up to 20 months .

• Duration of Response (DoR) to the combination of ipatasertib with HP (+/- ET) as maintenance therapy after first line treatment for HER2-positive metastatic BC with a taxane plus HP.

  From date of randomization to disease progression, death, unacceptable toxicity, consent withdrawal or study termination, whichever came first, assessed up to 20 months .

• Clinical Benefit Rate (CBR) of the combination of ipatasertib with HP (+/- ET) as maintenance therapy after first line treatment for HER2-positive metastatic BC with a taxane plus HP.

  From date of randomization to disease progression, death, unacceptable toxicity, consent withdrawal or study termination, whichever came first, assessed up to 20 months .

Other Outcomes (11)

• To identify putative predictive and prognostic molecular biomarkers (in plasma and/or tumoral tissue) that might be associated with the therapeutic activity of the combination of ipatasertib with HP (+/- ET).

  From date of randomization to treatment discontinuation (up to 20 months)

• To identify molecular mechanisms of resistance to the study treatment by analyzing genomic DNA and gene expression in FFPE tumoral tissue before study treatment and after progression of disease (PD).

  From date of randomization to treatment discontinuation (up to 20 months)

• To identify molecular mechanisms of resistance to the study treatment by analyzing circulating tumoral DNA (ctDNA) before study treatment and after progression of disease (PD).

  From date of randomization to treatment discontinuation (up to 20 months)

Study Arms (1)

Ipatasertib + Trastuzumab + Pertuzumab

EXPERIMENTAL

Ipatasertib will be given from Day 1 to Day 21 in every 28-day cycles. The starting dose is 400 mg orally (PO) QD and may be decreased to 300 mg QD and further to 200 mg QD (dose levels 1, - 1 and -2, respectively). Pertuzumab will be given IV every 21 days at the dose of 420 mg. Trastuzumab will be given SC every 21 days at the dose of 600mg. Intravenous (IV) Trastuzumab

Drug: Ipatasertib; Drug: Trastuzumab; Drug: Pertuzumab

Interventions

Pertuzumab DRUG

420 mg every 3 weeks

Also known as: Perjecta

Ipatasertib + Trastuzumab + Pertuzumab

Ipatasertib DRUG

Ipatasertib will be administered orally once a day, beginning on Cycle 1, Day 1 through Day 21 of each 28-day cycle.

Also known as: GDC-0068

Ipatasertib + Trastuzumab + Pertuzumab

Trastuzumab DRUG

600 mg every 3 weeks

Also known as: Herceptin

Ipatasertib + Trastuzumab + Pertuzumab

Eligibility Criteria

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

You may qualify if:

• Written and signed informed consent for all study procedures according to local regulatory requirements prior to beginning of specific protocol procedures.
• Female (pre- or postmenopausal) or male patients.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Confirmed HER2-positive invasive breast cancer by central determination defined by American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) clinical practice guidelines. (Wolff el al. Arch Pathol Lab Med-Vol 142, November 2018;).
• Known hormone receptor status, as assessed locally, defined by ASCO/CAP clinical practice guidelines. ER/PR positivity is defined as the presence of ≥ 1% of tumor cells with nuclear staining (Hammond et al. JCO 2010).
• Histologically confirmed, locally advanced or metastatic adenocarcinoma of the breast.
• Patients with unresectable locally advanced disease must have recurrent or progressive disease, which must not be amenable to resection with curative intent. Patients with available standard curative options are not eligible.
• For patients with bilateral breast cancer, HER2-positivity must be demonstrated in both locations or in a metastatic biopsy.
• Patient must be a candidate to receive maintenance HP after first line treatment for metastatic disease with at least 4 cycles of taxane plus HP.
• Prior taxane must have been discontinued for a reason other than progressive disease.
• Patients may or may not have received neo/adjuvant therapy but must have a disease-free interval from completion of anti-HER2 therapy to metastatic diagnosis ≥6 months.
• PIK3CA mutation identified and confirmed in tumor tissue or plasma ctDNA by central determination.
• Start of treatment with ipatasertib plus HP no later than 9 weeks after last dose of taxane plus HP (i.e., maximum of 2 HP administrations with no taxane).
• Willingness and ability to provide archived formalin fixed paraffin embedded (FFPE) tissue block.

You may not qualify if:

• Last dose of taxane plus HP given more than 9 weeks prior to C1D1.
• Prior malignancy within 3 years prior to randomization, except curatively treated non-melanoma skin, carcinoma in situ of the cervix or Stage I uterine cancer.
• Brain metastases that have not been treated previously, are progressive, or require any type of therapy (e.g., radiation, surgery, or steroids) to control symptoms within 30 days prior to the first study treatment dose.
• Radiotherapy for metastatic sites of disease outside of the brain performed within 14 days prior to study enrollment and/or radiation of \>30% of marrow-bearing bone.
• Symptomatic hypercalcemia requiring use of bisphosphonate or RANKL inhibitors therapy within 21 days prior to the first study treatment. Patients who receive bisphosphonate therapy specifically to prevent skeletal events are eligible if they have been initiated prior to the treatment to study.
• Cardiopulmonary dysfunction as defined by:
• Inadequately controlled angina or serious cardiac arrhythmia not controlled by adequate medication.
• Inadequate LVEF at baseline, as defined as LVEF \<50% by either ECHO or MUGA scan.
• History of symptomatic congestive heart failure (CHF): Grade ≥3 per NCI CTCAE version 4.03 or Class ≥II New York Health Association (NYHA) criteria.
• History of a decrease in LVEF to \<40% or symptomatic CHF with prior trastuzumab or HP treatment.
• History of myocardial infarction within 6 months prior to randomization.
• Current dyspnea at rest due to complications of advanced malignancy, or other disease requiring continuous oxygen therapy.
• Congenital long QT syndrome or screening QT interval corrected using Fridericia's formula (QTcF) \> 480 milliseconds.
• Concurrent, serious, uncontrolled infections or current known infection with HIV (testing is not mandatory).
• History of intolerance, including Grade 3-4 infusion reaction or hypersensitivity, to trastuzumab or pertuzumab.

Sponsors & Collaborators

• SOLTI Breast Cancer Research Group: lead
• Roche Pharma AG: collaborator

Study Sites (10)

ICO Badalona

Badalona, Barcelona, Spain

Location

Hospital Universitario del Vall d' Hebron

Barcelona, Barcelona, Spain

Location

Comp. Hosp.Univ. Santiago (Chus)

Santiago de Compostela, La Coruña, Spain

Location

H.Univ. Arnau de Vilanova de Lleida

Lleida, Lleida, Spain

Location

Centro Integral Oncológico Clara Campal (CIOCC)

Madrid, Madrid, Spain

Location

Hospital Universitario Doce de Octubre

Madrid, Madrid, Spain

Location

MD Anderson

Madrid, Madrid, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, Sevilla, Spain

Location

Hospital Virgen de Macarena

Seville, Sevilla, Spain

Location

Fundación Instituto Valenciano de Oncología

Valencia, Valencia, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ipatasertib; Trastuzumab; pertuzumab

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

Study Design

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

Study Record Dates

• First Submitted: January 17, 2020
• First Posted: February 5, 2020
• Study Start: February 25, 2020
• Primary Completion: December 5, 2021
• Study Completion: June 17, 2025
• Last Updated: March 16, 2026

Record last verified: 2026-03

Locations

ES (10)