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

• Register: ClinicalTrials.gov
• Last refreshed on: 25 March 2024
• Main ID: NCT03424005
• Date of registration: 30/01/2018
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer Morpheus-panBC
• Scientific 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)
• Date of first enrolment: April 2, 2018
• Target sample size: 242
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03424005
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

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

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

• Name: Reference Study ID Number: CO40115 https://forpatients.roche.com/

Key inclusion & exclusion criteria

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
- 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
- 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 better with the exception of alopecia of any grade and Grade 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Breast Cancer

Intervention(s)

Drug: Capecitabine

Drug: Atezolizumab

Drug: Bevacizumab

Drug: Inavolisib

Drug: Ribociclib

Drug: Selicrelumab

Drug: SGN-LIV1A

Drug: Ipatasertib

Drug: Tocilizumab

Drug: Abemaciclib

Drug: Chemotherapy (Gemcitabine + Carboplatin or Eribulin)

Drug: Fulvestrant

Drug: Inavolisib (9 mg)

Drug: Inavolisib (6 mg)

Drug: Sacituzumab Govitecan

Drug: Nab-Paclitaxel

Drug: Trastuzumab Deruxtecan

Primary Outcome(s)

Objective Response Rate (ORR) [Time Frame: Baseline until disease progression or loss of clinical benefit (up to approximately 8 years)]

Number of Participants With Adverse Events [Time Frame: Baseline to end of study (up to approximately 8 years)]

Secondary Outcome(s)

Overall Survival (at specific time-points) [Time Frame: 12 and 18 months]

Disease Control Rate (DCR) [Time Frame: Baseline through end of study (up to approximately 8 years)]

Overall Survival (OS) [Time Frame: Randomization to death from any cause, through the end of study (up to approximately 8 years)]

Duration of Response (DOR) [Time Frame: 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)]

Progression Free Survival (PFS) [Time Frame: 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 ID(s)

2017-002038-21

CO40115

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Seagen Inc.

Gilead Sciences