A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer

Breast Cancer Clinical Trial

— Morpheus-panBC  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03424005
• Other study ID #: CO40115
• Secondary ID: 2017-002038-21
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 2, 2018
• Est. completion date: May 3, 2026

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: CO40115 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. and Canada)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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, four 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-naive cohort).

Cohort 3 will consist of participants with locally-advanced or metastatic HR+, HER2-negative disease with PIK3CA mutation who may or may not have had disease progression during or following previous lines of treatment for metastatic disease (HR+cohort).

Cohort 4 will consist of participants with locally-advanced or metastatic HER2+ /HER2-low disease with PIK3CA mutation 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). In addition, 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 (Stage 2), provided Stage 2 is open for enrollment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 242
• Est. completion date: May 3, 2026
• Est. primary completion date: May 3, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

• 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

Inclusion criteria for Cohort 1

• Metastatic or inoperable locally advanced, histologically documented TNBC

• No prior systemic treatment for metastatic or inoperable locally advanced TNBC

• Positive PD-L1 expression, defined as >/= 1% of the tumor area occupied by PD L1-expressing tumor-infiltrating immune cells of any intensity, as determined through use of the U.S. Food and Drug Administration-approved or CE-marked Ventana PD-L1 (SP142) Assay

Inclusion criteria for Cohort 2

• Metastatic or inoperable locally advanced, histologically documented TNBC

• Eligible for capecitabine monotherapy

• Radiologic/objective evidence of recurrence or disease progression after 1L treatment with chemotherapy, for a total of one line of therapy for inoperable locally advanced or metastatic breast cancer

Inclusion criteria for Cohort 3

• Metastatic or inoperable locally-advanced, histologically documented HR+ breast cancer who had previous lines of treatment for metastatic disease.

• Fasting glucose < 126 mg/dL or < 7.0 mmol/L and HbA1c </= 6.4%

• Confirmation of PIK3CA mutation

• Patients for whom ET (e.g., fulvestrant) is recommended and treatment with cytotoxic chemotherapy is not indicated at time of entry into the study, as per national or local treatments standards

• Postmenopausal, or premenopausal/perimenopausal status and willing to undergo and maintain treatment with approved LHRH-agonist (also known as gonadotropin-releasing hormone-agonist) therapy for the duration of study

Inclusion criteria for Cohort 4

• Left ventricular ejection fraction, measured by echocardiogram or radionucleotide ventriculography, greater than 50%

• Confirmation of HER2+ or HER2-low status Fasting glucose < 126 mg/dL or < 7.0 mmol/L and HbA1c </= 6.4%

• Confirmation of PIK3CA mutation

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

• Treatment with investigational therapy within 28 days prior to initiation of study treatment

• 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

• 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

• Eligibility only for the control arm

Exclusion Criteria for Stage 1 (both cohorts) and Stage 2 (2L CIT-naïve cohort)

• 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

• 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

• Pregnancy or breastfeeding, or intention of becoming pregnant during the study

Exclusion Criteria for the 2L CIT-naive cohort, Stage 1

• Prior treatment with capecitabine,

• Treatment with sorivudine or its chemically related analogues, such as brivudine

• History of severe and unexpected reactions to fluoropyrimidine therapy

• Known complete absence of dihydropyrimidine dehydrogenase activity

Exclusion Criteria for Stage 2

• Inability to tolerate atezolizumab during Stage 1

• For patients receiving eribulin: congenital long QT syndrome

Additional drug-specific exclusion criteria may apply to Stage 1 and 2.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Capecitabine
Capecitabine will be administered 1250 mg/m^2 orally twice daily on Days 1-14, of each 21 day cycle.
• Atezolizumab
For Atezolizumab (Atezo) + SGN-LIV1A, Atezo + Sacituzumab Govitecan, or Atezo + Chemo arms: atezolizumab will be administered intravenously (IV), 1200 mg, on Day 1 of each 21-day cycle. For Atezo + Nab-Paclitaxel, Atezo + Selicrelumab + Bevacizumab, Atezo + Ipatasertib, or Atezo + Nab-Paclitaxel + Tocilizumab: atezolizumab will be administered IV, 840 mg on Days 1 and 15, of each 28-day cycle.
• Ipatasertib
Ipatasertib will be administered by mouth 400 mg once a day, on Day 1-21 of each 28 day cycle.
• SGN-LIV1A
SGN-LIV1A will be administered IV, 2.5 mg/kg (maximum calculated dose 250 mg), on Day 1 of each 21 day cycle.
• Bevacizumab
Bevacizumab will be administered IV, 10 mg/kg, on Days 1 and 15 of each 28 day cycle.
• Chemotherapy (Gemcitabine + Carboplatin or Eribulin)
Gemcitabine will be administered by IV, 1000 mg/m^2, along with carboplatin, by IV, AUC 2, on Days 1 and 8 of each 21 day cycle. Or Eribulin will be administered by IV, 1.4 mg/m^2 on days 1 and 8 of each 21 day cycle.
• Selicrelumab
Selicrelumab will be administered by subcutaneous (SC) injection at a fixed dose of 16 mg on Day 1 of Cycles 1 to 4 and every third cycle thereafter (cycle = 28 days).
• Tocilizumab
Tocilizumab will be administered IV, 8 mg/kg infusion on Day 1 of each 28 day cycle.
• Nab-Paclitaxel
Nab-Paclitaxel will be administered by IV, 100 mg/m^2, on Days 1, 8, and 15 of each 28-day cycle.
• Sacituzumab Govitecan
Sacituzumab govitecan will be administered by IV, 10 mg/kg, on Days 1 and 8 of each 21-day cycle.
• Abemaciclib
Abemaciclib tablets will be administered at a dose of 150 mg twice daily by mouth on Days 1-28 of each cycle (cycle=28 days).
• Fulvestrant
Fulvestrant IM injection at a dose of 500 mg will be administered on Days 1 and 15 of Cycle 1, and then on Day 1 of each cycle thereafter (cycle=28 days).
• Ribociclib
Ribociclib tablets of 400 mg will be administered by mouth on Days 1-21 of each 28-day cycle.
• Inavolisib
Inavolisib tablets will be administered at a dose of 9 mg by mouth on Days 1-28 of each cycle (cycle = 28 days).
• Inavolisib (9 mg)
Inavolisib tablets will be administered at a dose of 9 mg by mouth on Days 1-21 of each cycle (cycle = 21 days).
• Inavolisib (6 mg)
Inavolisib tablets will be administered at a dose of 6 mg by mouth on Days 1-21 of each cycle (cycle = 21 days).
• Trastuzumab Deruxtecan
Trastuzumab Deruxtecan will be administered at a dose of 5.4 mg/kg by IV infusion on Day 1 of each 21-day cycle.

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Centre-East Melbourne	Melbourne	Victoria
Australia	Fiona Stanley Hospital - Medical Oncology	Murdoch	Western Australia
France	Centre Léon Bérard	Lyon
France	Institut régional du Cancer Montpellier	Montpellier
France	Institut Universitaire du Cancer de Toulouse-Oncopole	Toulouse
France	Gustave Roussy	Villejuif
Germany	Universitätsklinikum Erlangen; Frauenklinik	Erlangen
Germany	Universitätsklinikum Essen	Essen
Israel	Hadassah University Medical Center	Jerusalem
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Rabin MC; Davidof Center - Oncology Institute	Petach Tikva
Israel	Sheba Medical Center	Ramat Gan
Israel	Tel-Aviv Sourasky Medical Center	Tel Aviv
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	University of Ulsan College of Medicine - Asan Medical Center	Seoul
Spain	Hospital del Mar	Barcelona
Spain	Vall d?Hebron Institute of Oncology (VHIO), Barcelona	Barcelona
Spain	Centro Integral Oncológico Clara Campal Ensayos Clínicos START	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Universitario Virgen Macarena	Sevilla
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Barts Health NHS Trust - St Bartholomew's Hospital	London
United States	City of Hope	Duarte	California
United States	The West Clinic; West Cancer Center	Germantown	Tennessee
United States	Hackensack Univ Medical Center; John Theurer Cancer Ctr	Hackensack	New Jersey
United States	Regional Cancer Care Associates, LLC	Howell	New Jersey
United States	University of California San Diego Medical Center; Moores Cancer Center	La Jolla	California
United States	Rocky Mountain Cancer Center - Longmont	Longmont	Colorado
United States	Vanderbilt University Medical Center; Vanderbilt University	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	NYU Langone Medical Center; NYU Perlmutter Cancer Center	New York	New York
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Texas Oncology-Plano East	Plano	Texas
United States	Stanford Cancer Institute	Stanford	California
United States	H. Lee Moffitt Cancer Center and Research Inst.	Tampa	Florida

Sponsors (3)

Lead Sponsor	Collaborator
Hoffmann-La Roche	Gilead Sciences, Seagen Inc.

Countries where clinical trial is conducted

United States,  Australia,  France,  Germany,  Israel,  Korea, Republic of,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR)		Baseline until disease progression or loss of clinical benefit (up to approximately 8 years)
Primary	Number of Participants With Adverse Events		Baseline to end of study (up to approximately 8 years)
Secondary	Progression Free Survival (PFS)		Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (up to approximately 8 years) as determined by the investigator according to RECIST v1.1
Secondary	Disease Control Rate (DCR)		Baseline through end of study (up to approximately 8 years)
Secondary	Overall Survival (OS)		Randomization to death from any cause, through the end of study (up to approximately 8 years)
Secondary	Overall Survival (at specific time-points)		12 and 18 months
Secondary	Duration of Response (DOR)		Randomization until first occurrence of a documented objective response to the first recorded occurrence of disease progression or death from any cause (whichever occurs first), through end of study (up to approximately 8 years)