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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03424005




Registration number
NCT03424005
Ethics application status
Date submitted
30/01/2018
Date registered
6/02/2018
Date last updated
7/06/2024

Titles & IDs
Public title
A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer
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)
Secondary ID [1] 0 0
2017-002038-21
Secondary ID [2] 0 0
CO40115
Universal Trial Number (UTN)
Trial acronym
Morpheus-panBC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Capecitabine
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Ipatasertib
Treatment: Drugs - SGN-LIV1A
Treatment: Drugs - Bevacizumab
Treatment: Drugs - Chemotherapy (Gemcitabine + Carboplatin or Eribulin)
Treatment: Drugs - Selicrelumab
Treatment: Drugs - Tocilizumab
Treatment: Drugs - Nab-Paclitaxel
Treatment: Drugs - Sacituzumab Govitecan
Treatment: Drugs - Abemaciclib
Treatment: Drugs - Fulvestrant
Treatment: Drugs - Ribociclib
Treatment: Drugs - Inavolisib
Treatment: Drugs - Inavolisib (9 mg)
Treatment: Drugs - Inavolisib (6 mg)
Treatment: Drugs - Trastuzumab Deruxtecan

Active Comparator: Atezolizumab + Nab-Paclitaxel - 1L PD-L1-positive participants will receive doublet combination treatment with atezolizumab + nab-paclitaxel until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Enrollment is closed.

Experimental: Atezolizumab + Nab-Paclitaxel + Tocilizumab - 1L PD-L1-positive participants will receive combination treatment with atezolizumab plus nab-paclitaxel and tocilizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Enrollment is closed.

Experimental: Atezolizumab + Sacituzumab Govitecan - 1L PD-L1-positive participants will receive doublet combination treatment with atezolizumab plus sacituzumab govitecan until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Enrollment is closed.

Active Comparator: Capecitabine - 2L CIT-naive participants will receive capecitabine until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1).
Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria.
Enrollment is closed.

Experimental: Atezolizumab + Ipatasertib - 2L CIT-naive participants will receive doublet combination treatment with atezolizumab + ipatasertib until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria.
Enrollment is closed.

Experimental: Atezolizumab + SGN-LIV1A - 2L CIT-naive participants will receive doublet combination treatment with atezolizumab plus SGNLIV1A until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria.
Enrollment is closed.

Experimental: Atezolizumab + Selicrelumab + Bevacizumab - 2L-CIT-naive participants will receive doublet combination treatment with atezolizumab plus selicrelumab and bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria.
Enrollment is closed.

Experimental: Atezolizumab + Chemo (Gemcitabine + Carboplatin or Eribulin) - 2L CIT-naive participants enrolled in the active comparator arm who experience disease progression per RECIST v1.1 and 2L CIT-naive participants enrolled in an experimental arm who experience loss of clinical benefit as determined by the investigator may receive doublet combination treatment with atezolizumab plus chemotherapy (gemcitabine + carboplatin or eribulin) until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Enrollment is closed.

Experimental: Inavolisib + Abemaciclib + Fulvestrant - Hormone receptor-positive (HR+) participants will receive treatment with inavolisib plus abemaciclib plus fulvestrant until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).

Experimental: Inavolisib + Ribociclib + Fulvestrant - Hormone receptor-positive (HR+) participants will receive treatment with inavolisib plus ribociclib plus fulvestrant until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).

Experimental: Inavolisib (6 mg) + Trastuzumab Deruxtecan - HER2+/HER2-low participants will receive inavolisib (6 mg) + trastuzumab deruxtecan until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.

Experimental: Inavolisib (9 mg) + Trastuzumab Deruxtecan - HER2+/HER2-low participants will receive inavolisib (9 mg) + trastuzumab deruxtecan until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.


Treatment: Drugs: Capecitabine
Capecitabine will be administered 1250 mg/m^2 orally twice daily on Days 1-14, of each 21 day cycle.

Treatment: Drugs: 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.

Treatment: Drugs: Ipatasertib
Ipatasertib will be administered by mouth 400 mg once a day, on Day 1-21 of each 28 day cycle.

Treatment: Drugs: 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.

Treatment: Drugs: Bevacizumab
Bevacizumab will be administered IV, 10 mg/kg, on Days 1 and 15 of each 28 day cycle.

Treatment: Drugs: 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.

Treatment: Drugs: 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).

Treatment: Drugs: Tocilizumab
Tocilizumab will be administered IV, 8 mg/kg infusion on Day 1 of each 28 day cycle.

Treatment: Drugs: Nab-Paclitaxel
Nab-Paclitaxel will be administered by IV, 100 mg/m^2, on Days 1, 8, and 15 of each 28-day cycle.

Treatment: Drugs: Sacituzumab Govitecan
Sacituzumab govitecan will be administered by IV, 10 mg/kg, on Days 1 and 8 of each 21-day cycle.

Treatment: Drugs: 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).

Treatment: Drugs: 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).

Treatment: Drugs: Ribociclib
Ribociclib tablets of 400 mg will be administered by mouth on Days 1-21 of each 28-day cycle.

Treatment: Drugs: Inavolisib
Inavolisib tablets will be administered at a dose of 9 mg by mouth on Days 1-28 of each cycle (cycle = 28 days).

Treatment: Drugs: 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).

Treatment: Drugs: 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).

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
Baseline until disease progression or loss of clinical benefit (up to approximately 8 years)
Primary outcome [2] 0 0
Number of Participants With Adverse Events
Timepoint [2] 0 0
Baseline to end of study (up to approximately 8 years)
Secondary outcome [1] 0 0
Progression Free Survival (PFS)
Timepoint [1] 0 0
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 outcome [2] 0 0
Disease Control Rate (DCR)
Timepoint [2] 0 0
Baseline through end of study (up to approximately 8 years)
Secondary outcome [3] 0 0
Overall Survival (OS)
Timepoint [3] 0 0
Randomization to death from any cause, through the end of study (up to approximately 8 years)
Secondary outcome [4] 0 0
Overall Survival (at specific time-points)
Timepoint [4] 0 0
12 and 18 months
Secondary outcome [5] 0 0
Duration of Response (DOR)
Timepoint [5] 0 0
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)

Eligibility
Key inclusion 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 </= 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

- 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/04/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
3/05/2026
Actual
Sample size
Target
242
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre-East Melbourne - Melbourne
Recruitment hospital [2] 0 0
Fiona Stanley Hospital - Medical Oncology - Murdoch
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment postcode(s) [2] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
New Jersey
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
France
State/province [9] 0 0
Lyon
Country [10] 0 0
France
State/province [10] 0 0
Montpellier
Country [11] 0 0
France
State/province [11] 0 0
Toulouse
Country [12] 0 0
France
State/province [12] 0 0
Villejuif
Country [13] 0 0
Germany
State/province [13] 0 0
Erlangen
Country [14] 0 0
Germany
State/province [14] 0 0
Essen
Country [15] 0 0
Israel
State/province [15] 0 0
Jerusalem
Country [16] 0 0
Israel
State/province [16] 0 0
Petach Tikva
Country [17] 0 0
Israel
State/province [17] 0 0
Ramat Gan
Country [18] 0 0
Israel
State/province [18] 0 0
Tel Aviv
Country [19] 0 0
Korea, Republic of
State/province [19] 0 0
Seoul
Country [20] 0 0
Spain
State/province [20] 0 0
Barcelona
Country [21] 0 0
Spain
State/province [21] 0 0
Madrid
Country [22] 0 0
Spain
State/province [22] 0 0
Sevilla
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Glasgow
Country [24] 0 0
United Kingdom
State/province [24] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Seagen Inc.
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Gilead Sciences
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03424005
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: CO40115 https://forpatients.roche.com/
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. and Canada)
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03424005