Informations générales (source: ClinicalTrials.gov)
A Phase Ib/II, Open-label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic Breast Cancer (Morpheus-panBC)
Interventional
Phase 1/Phase 2
Hoffmann-La Roche (Voir sur ClinicalTrials)
mars 2018
septembre 2030
02 avril 2026
This is an umbrella study evaluating the efficacy and safety of multiple treatment
combinations in participants with metastatic or inoperable locally advanced breast
cancer.
The study will be performed in two stages. During Stage 1, six cohorts will be enrolled
in parallel in this study:
Cohort 1 will consist of programmed death-ligand 1 (PD-L1)-positive participants who have
received no prior systemic therapy for metastatic or inoperable locally advanced
triple-negative breast cancer (TNBC) (first-line [1L] PD-L1+ cohort).
Cohort 2 will consist of participants who had disease progression during or following 1L
treatment with chemotherapy for metastatic or inoperable locally-advanced TNBC and have
not received cancer immunotherapy (CIT) (second-line [2L] CIT-naïve cohort).
Cohort 3, 5, and 6 will consist of participants with locally advanced or metastatic
hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative
disease with one or more PIK3CA mutations.
Cohort 4 will consist of participants with locally advanced or metastatic HER2+ /HER2-low
disease with one or more PIK3CA mutations who had disease progression on standard-of-care
therapies (HER2+ /HER2-low cohort).
In each cohort, eligible participants will initially be assigned to one of several
treatment arms (Stage 1). During Stage 2, participants in the 2L CIT-naïve cohort who
experience disease progression, loss of clinical benefit, or unacceptable toxicity during
Stage 1 may be eligible to continue treatment with a different treatment combination,
provided Stage 2 is open for enrollment and all eligibility criteria are met.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Joana Mourato RIBEIRO | 17/04/2026 12:40:05 | Contacter | ||
Critères
Tous
Inclusion Criteria
Patients must meet all of the following criteria to qualify for Stage 1 (all cohorts) and
to qualify for Stage 2 (2L CIT-naïve cohort):
- Age >/= 18 years at the time of signing Informed Consent Form
- Eastern cooperative oncology group (ECOG) performance status of 0 or 1
- Able to comply with the study protocol, in the investigator's judgment
- Metastatic or inoperable locally advanced breast cancer
- Measurable disease (at least one target lesion) according to RECIST v1.1
- Life expectancy >/= 3 months, as determined by the investigator
- Tumor accessible for biopsy, unless archival tissue is available
- Availability of a representative tumor specimen that is suitable for biomarker
analysis via central testing
- Adequate hematologic and end-organ function, defined by the following laboratory
test results, obtained within 14 days prior to initiation of study treatment
- For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive measures and agreement to refrain
from breastfeeding and donating eggs, as outlined for each specific treatment arm
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or
use contraceptive measures, and agreement to refrain from donating sperm, as
outlined for each specific treatment arm
Exclusion Criteria
Exclusion Criteria for Stage 1
- Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies,
including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, CD40
agonists or interleukin-2 (IL-2) or IL-2-like compounds
- Biologic treatment (e.g., bevacizumab) within 2 weeks prior to initiation of study
treatment, or other systemic treatment for TNBC within 2 weeks or 5 half-lives of
the drug (whichever is longer) prior to initiation of study treatment
- Treatment with systemic immunosuppressive medication (including, but not limited to,
corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and
anti-tumor necrosis factor alpha agents) within 2 weeks prior to initiation of study
treatment, or anticipation of need for systemic immunosuppressive medication during
the course of the study
- Eligibility only for the control arm
Exclusion Criteria for Stage 1 (both cohorts) and Stage 2 (2L CIT-naïve cohort)
- Adverse events from prior anti-cancer therapy that have not resolved to Grade </= 1
or better with the exception of alopecia of any grade and Grade </= 2 peripheral
neuropathy
- Treatment with investigational therapy within 28 days prior to initiation of study
treatment
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures (once monthly or more frequently)
- Uncontrolled tumor-related pain
- Symptomatic, untreated, or actively progressing central nervous system (CNS)
metastases
- History of leptomeningeal disease
- Active or history of autoimmune disease or immune deficiency
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of
active pneumonitis on screening chest computed tomography (CT) scan. History of
radiation pneumonitis in the radiation field (fibrosis) is permitted.
- Active tuberculosis
- Severe infection within 4 weeks prior to initiation of study treatment
- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation
of study treatment
- Significant cardiovascular disease
- Prior allogeneic stem cell or solid organ transplantation
- History of malignancy other than breast cancer within 2 years prior to screening,
with the exception of those with a negligible risk of metastasis or death
- Pregnancy or breastfeeding, or intention of becoming pregnant during the study
Patients must meet all of the following criteria to qualify for Stage 1 (all cohorts) and
to qualify for Stage 2 (2L CIT-naïve cohort):
- Age >/= 18 years at the time of signing Informed Consent Form
- Eastern cooperative oncology group (ECOG) performance status of 0 or 1
- Able to comply with the study protocol, in the investigator's judgment
- Metastatic or inoperable locally advanced breast cancer
- Measurable disease (at least one target lesion) according to RECIST v1.1
- Life expectancy >/= 3 months, as determined by the investigator
- Tumor accessible for biopsy, unless archival tissue is available
- Availability of a representative tumor specimen that is suitable for biomarker
analysis via central testing
- Adequate hematologic and end-organ function, defined by the following laboratory
test results, obtained within 14 days prior to initiation of study treatment
- For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive measures and agreement to refrain
from breastfeeding and donating eggs, as outlined for each specific treatment arm
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or
use contraceptive measures, and agreement to refrain from donating sperm, as
outlined for each specific treatment arm
Exclusion Criteria
Exclusion Criteria for Stage 1
- Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies,
including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, CD40
agonists or interleukin-2 (IL-2) or IL-2-like compounds
- Biologic treatment (e.g., bevacizumab) within 2 weeks prior to initiation of study
treatment, or other systemic treatment for TNBC within 2 weeks or 5 half-lives of
the drug (whichever is longer) prior to initiation of study treatment
- Treatment with systemic immunosuppressive medication (including, but not limited to,
corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and
anti-tumor necrosis factor alpha agents) within 2 weeks prior to initiation of study
treatment, or anticipation of need for systemic immunosuppressive medication during
the course of the study
- Eligibility only for the control arm
Exclusion Criteria for Stage 1 (both cohorts) and Stage 2 (2L CIT-naïve cohort)
- Adverse events from prior anti-cancer therapy that have not resolved to Grade </= 1
or better with the exception of alopecia of any grade and Grade </= 2 peripheral
neuropathy
- Treatment with investigational therapy within 28 days prior to initiation of study
treatment
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures (once monthly or more frequently)
- Uncontrolled tumor-related pain
- Symptomatic, untreated, or actively progressing central nervous system (CNS)
metastases
- History of leptomeningeal disease
- Active or history of autoimmune disease or immune deficiency
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of
active pneumonitis on screening chest computed tomography (CT) scan. History of
radiation pneumonitis in the radiation field (fibrosis) is permitted.
- Active tuberculosis
- Severe infection within 4 weeks prior to initiation of study treatment
- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation
of study treatment
- Significant cardiovascular disease
- Prior allogeneic stem cell or solid organ transplantation
- History of malignancy other than breast cancer within 2 years prior to screening,
with the exception of those with a negligible risk of metastasis or death
- Pregnancy or breastfeeding, or intention of becoming pregnant during the study