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

Primary Purpose

Breast Cancer

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Capecitabine
Atezolizumab
Ipatasertib
SGN-LIV1A
Bevacizumab
Chemotherapy (Gemcitabine + Carboplatin or Eribulin)
Selicrelumab
Tocilizumab
Nab-Paclitaxel
Sacituzumab Govitecan
Abemaciclib
Fulvestrant
Ribociclib
Inavolisib
Inavolisib (9 mg)
Inavolisib (6 mg)
Trastuzumab Deruxtecan
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria Stage 1

  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Metastatic or inoperable locally advanced, histologically documented TNBC (absence of HER2, ER, and PR expression)
  • For the 1L PD L1+ cohort: no prior systemic treatment for metastatic or inoperable locally advanced TNBC
  • For the 2L CIT-naive cohort: Eligible for capecitabine monotherapy
  • For the 2L CIT-naive cohort: 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
  • Life expectancy =/> 3 months, as determined by the investigator
  • Tumor accessible for biopsy
  • Availability of a representative tumor specimen that is suitable for determination of PD-L1 and/or additional biomarker status via central testing
  • For the 1L PD L1+ cohort: 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 Stage 1 (both cohorts) and Stage 2 (2L CIT-naive cohort)

  • Measurable disease (at least one target lesion)
  • Adequate hematologic and end-organ function, laboratory test results, obtained within 14 days prior to initiation of study treatment.
  • Negative HIV test at screening
  • Negative hepatitis B surface antigen test
  • Negative total hepatitis B core antibody (HBcAb)
  • Negative hepatitis C virus (HCV) antibody test at screening
  • 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 Stage 2 (2L CIT-naive cohort)

  • ECOG Performance Status of 0, 1, or 2
  • Patients randomly allocated to the control arm during Stage 1: ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity, provided that Medical Monitor approval for entry into Stage 2 is obtained, or disease progression per RECIST v1.1 while receiving control treatment
  • Patients randomly allocated to an experimental arm during Stage 1: ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity not related to atezolizumab, disease progression per RECIST v1.1, or loss of clinical benefit as determined by the investigator while receiving Stage 1 treatment
  • Availability of a tumor specimen from a biopsy performed upon discontinuation of Stage 1 (if deemed clinically feasible by the investigator)

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

Sites / Locations

  • City of HopeRecruiting
  • University of California San Diego Medical Center; Moores Cancer Center
  • Stanford Cancer Institute
  • Rocky Mountain Cancer Center - Longmont
  • H. Lee Moffitt Cancer Center and Research Inst.
  • Hackensack Univ Medical Center; John Theurer Cancer Ctr
  • Regional Cancer Care Associates, LLC
  • Rutgers Cancer Institute of New Jersey
  • NYU Langone Medical Center; NYU Perlmutter Cancer Center
  • Thomas Jefferson University Hospital
  • University of Pittsburgh Medical Center
  • The West Clinic; West Cancer CenterRecruiting
  • Vanderbilt University Medical Center; Vanderbilt UniversityRecruiting
  • Texas Oncology-Plano East
  • Peter MacCallum Cancer Centre-East MelbourneRecruiting
  • Fiona Stanley Hospital - Medical OncologyRecruiting
  • Centre Léon Bérard
  • Institut régional du Cancer Montpellier
  • Institut Universitaire du Cancer de Toulouse-OncopoleRecruiting
  • Gustave Roussy
  • Universitätsklinikum Erlangen; Frauenklinik
  • Universitätsklinikum Essen
  • Shaare Zedek Medical Center
  • Hadassah University Medical CenterRecruiting
  • Rabin MC; Davidof Center - Oncology InstituteRecruiting
  • Sheba Medical CenterRecruiting
  • Tel-Aviv Sourasky Medical CenterRecruiting
  • Seoul National University HospitalRecruiting
  • Severance HospitalRecruiting
  • University of Ulsan College of Medicine - Asan Medical CenterRecruiting
  • Hospital del MarRecruiting
  • Vall d?Hebron Institute of Oncology (VHIO), BarcelonaRecruiting
  • Hospital Universitario Ramon y CajalRecruiting
  • Centro Integral Oncológico Clara Campal Ensayos Clínicos STARTRecruiting
  • Hospital Universitario Virgen MacarenaRecruiting
  • Beatson West of Scotland Cancer Centre
  • Barts Health NHS Trust - St Bartholomew's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm Type

Active Comparator

Experimental

Experimental

Active Comparator

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Atezolizumab + Nab-Paclitaxel

Atezolizumab + Nab-Paclitaxel + Tocilizumab

Atezolizumab + Sacituzumab Govitecan

Capecitabine

Atezolizumab + Ipatasertib

Atezolizumab + SGN-LIV1A

Atezolizumab + Selicrelumab + Bevacizumab

Atezolizumab + Chemo (Gemcitabine + Carboplatin or Eribulin)

Inavolisib + Abemaciclib + Fulvestrant

Inavolisib + Ribociclib + Fulvestrant

Inavolisib (6 mg) + Trastuzumab Deruxtecan

Inavolisib (9 mg) + Trastuzumab Deruxtecan

Arm Description

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.

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.

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.

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.

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.

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.

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.

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.

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).

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).

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.

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.

Outcomes

Primary Outcome Measures

Objective Response Rate (ORR)
Number of Participants With Adverse Events

Secondary Outcome Measures

Progression Free Survival (PFS)
Disease Control Rate (DCR)
Overall Survival (OS)
Overall Survival (at specific time-points)
Duration of Response (DOR)

Full Information

First Posted
January 30, 2018
Last Updated
October 6, 2023
Sponsor
Hoffmann-La Roche
Collaborators
Seagen Inc., Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT03424005
Brief Title
A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer
Acronym
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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 2, 2018 (Actual)
Primary Completion Date
May 3, 2026 (Anticipated)
Study Completion Date
May 3, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
Collaborators
Seagen Inc., Gilead Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
242 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Atezolizumab + Nab-Paclitaxel
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Atezolizumab + Nab-Paclitaxel + Tocilizumab
Arm Type
Experimental
Arm Description
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.
Arm Title
Atezolizumab + Sacituzumab Govitecan
Arm Type
Experimental
Arm Description
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.
Arm Title
Capecitabine
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Atezolizumab + Ipatasertib
Arm Type
Experimental
Arm Description
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.
Arm Title
Atezolizumab + SGN-LIV1A
Arm Type
Experimental
Arm Description
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.
Arm Title
Atezolizumab + Selicrelumab + Bevacizumab
Arm Type
Experimental
Arm Description
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.
Arm Title
Atezolizumab + Chemo (Gemcitabine + Carboplatin or Eribulin)
Arm Type
Experimental
Arm Description
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.
Arm Title
Inavolisib + Abemaciclib + Fulvestrant
Arm Type
Experimental
Arm Description
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).
Arm Title
Inavolisib + Ribociclib + Fulvestrant
Arm Type
Experimental
Arm Description
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).
Arm Title
Inavolisib (6 mg) + Trastuzumab Deruxtecan
Arm Type
Experimental
Arm Description
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.
Arm Title
Inavolisib (9 mg) + Trastuzumab Deruxtecan
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
Capecitabine will be administered 1250 mg/m^2 orally twice daily on Days 1-14, of each 21 day cycle.
Intervention Type
Drug
Intervention Name(s)
Atezolizumab
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Ipatasertib
Intervention Description
Ipatasertib will be administered by mouth 400 mg once a day, on Day 1-21 of each 28 day cycle.
Intervention Type
Drug
Intervention Name(s)
SGN-LIV1A
Intervention Description
SGN-LIV1A will be administered IV, 2.5 mg/kg (maximum calculated dose 250 mg), on Day 1 of each 21 day cycle.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Intervention Description
Bevacizumab will be administered IV, 10 mg/kg, on Days 1 and 15 of each 28 day cycle.
Intervention Type
Drug
Intervention Name(s)
Chemotherapy (Gemcitabine + Carboplatin or Eribulin)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Selicrelumab
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Tocilizumab
Intervention Description
Tocilizumab will be administered IV, 8 mg/kg infusion on Day 1 of each 28 day cycle.
Intervention Type
Drug
Intervention Name(s)
Nab-Paclitaxel
Intervention Description
Nab-Paclitaxel will be administered by IV, 100 mg/m^2, on Days 1, 8, and 15 of each 28-day cycle.
Intervention Type
Drug
Intervention Name(s)
Sacituzumab Govitecan
Intervention Description
Sacituzumab govitecan will be administered by IV, 10 mg/kg, on Days 1 and 8 of each 21-day cycle.
Intervention Type
Drug
Intervention Name(s)
Abemaciclib
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Fulvestrant
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Ribociclib
Intervention Description
Ribociclib tablets of 400 mg will be administered by mouth on Days 1-21 of each 28-day cycle.
Intervention Type
Drug
Intervention Name(s)
Inavolisib
Other Intervention Name(s)
GDC-0077, RO7113755
Intervention Description
Inavolisib tablets will be administered at a dose of 9 mg by mouth on Days 1-28 of each cycle (cycle = 28 days).
Intervention Type
Drug
Intervention Name(s)
Inavolisib (9 mg)
Other Intervention Name(s)
GDC-0077, RO7113755
Intervention Description
Inavolisib tablets will be administered at a dose of 9 mg by mouth on Days 1-21 of each cycle (cycle = 21 days).
Intervention Type
Drug
Intervention Name(s)
Inavolisib (6 mg)
Other Intervention Name(s)
GDC-0077, RO7113755
Intervention Description
Inavolisib tablets will be administered at a dose of 6 mg by mouth on Days 1-21 of each cycle (cycle = 21 days).
Intervention Type
Drug
Intervention Name(s)
Trastuzumab Deruxtecan
Intervention Description
Trastuzumab Deruxtecan will be administered at a dose of 5.4 mg/kg by IV infusion on Day 1 of each 21-day cycle.
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Time Frame
Baseline until disease progression or loss of clinical benefit (approximately 5 years)
Title
Number of Participants With Adverse Events
Time Frame
Baseline to end of study (approximately 5 years)
Secondary Outcome Measure Information:
Title
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 (approximately 5 years) as determined by the investigator according to RECIST v1.1
Title
Disease Control Rate (DCR)
Time Frame
Baseline through end of study (approximately 5 years)
Title
Overall Survival (OS)
Time Frame
Randomization to death from any cause, through the end of study (approximately 5 years)
Title
Overall Survival (at specific time-points)
Time Frame
12 and 18 months
Title
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 (approximately 5 years)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Reference Study ID Number: CO40115 https://forpatients.roche.com/
Phone
888-662-6728 (U.S. and Canada)
Email
global-roche-genentech-trials@gene.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Name
University of California San Diego Medical Center; Moores Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Individual Site Status
Completed
Facility Name
Stanford Cancer Institute
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Individual Site Status
Suspended
Facility Name
Rocky Mountain Cancer Center - Longmont
City
Longmont
State/Province
Colorado
ZIP/Postal Code
80504
Country
United States
Individual Site Status
Completed
Facility Name
H. Lee Moffitt Cancer Center and Research Inst.
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Individual Site Status
Completed
Facility Name
Hackensack Univ Medical Center; John Theurer Cancer Ctr
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Individual Site Status
Completed
Facility Name
Regional Cancer Care Associates, LLC
City
Howell
State/Province
New Jersey
ZIP/Postal Code
07731
Country
United States
Individual Site Status
Completed
Facility Name
Rutgers Cancer Institute of New Jersey
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Individual Site Status
Completed
Facility Name
NYU Langone Medical Center; NYU Perlmutter Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Completed
Facility Name
Thomas Jefferson University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Individual Site Status
Completed
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Individual Site Status
Completed
Facility Name
The West Clinic; West Cancer Center
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Individual Site Status
Recruiting
Facility Name
Vanderbilt University Medical Center; Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Individual Site Status
Recruiting
Facility Name
Texas Oncology-Plano East
City
Plano
State/Province
Texas
ZIP/Postal Code
75075-7787
Country
United States
Individual Site Status
Completed
Facility Name
Peter MacCallum Cancer Centre-East Melbourne
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Individual Site Status
Recruiting
Facility Name
Fiona Stanley Hospital - Medical Oncology
City
Murdoch
State/Province
Western Australia
ZIP/Postal Code
6150
Country
Australia
Individual Site Status
Recruiting
Facility Name
Centre Léon Bérard
City
Lyon
ZIP/Postal Code
69008
Country
France
Individual Site Status
Active, not recruiting
Facility Name
Institut régional du Cancer Montpellier
City
Montpellier
ZIP/Postal Code
34298
Country
France
Individual Site Status
Suspended
Facility Name
Institut Universitaire du Cancer de Toulouse-Oncopole
City
Toulouse
ZIP/Postal Code
31059
Country
France
Individual Site Status
Recruiting
Facility Name
Gustave Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France
Individual Site Status
Suspended
Facility Name
Universitätsklinikum Erlangen; Frauenklinik
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Individual Site Status
Suspended
Facility Name
Universitätsklinikum Essen
City
Essen
ZIP/Postal Code
45147
Country
Germany
Individual Site Status
Suspended
Facility Name
Shaare Zedek Medical Center
City
Jerusalem
ZIP/Postal Code
9103102
Country
Israel
Individual Site Status
Suspended
Facility Name
Hadassah University Medical Center
City
Jerusalem
Country
Israel
Individual Site Status
Recruiting
Facility Name
Rabin MC; Davidof Center - Oncology Institute
City
Petach Tikva
ZIP/Postal Code
4941492
Country
Israel
Individual Site Status
Recruiting
Facility Name
Sheba Medical Center
City
Ramat Gan
ZIP/Postal Code
5262100
Country
Israel
Individual Site Status
Recruiting
Facility Name
Tel-Aviv Sourasky Medical Center
City
Tel Aviv
ZIP/Postal Code
6423906
Country
Israel
Individual Site Status
Recruiting
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Severance Hospital
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
University of Ulsan College of Medicine - Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Hospital del Mar
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
Individual Site Status
Recruiting
Facility Name
Vall d?Hebron Institute of Oncology (VHIO), Barcelona
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario Ramon y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Individual Site Status
Recruiting
Facility Name
Centro Integral Oncológico Clara Campal Ensayos Clínicos START
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario Virgen Macarena
City
Sevilla
ZIP/Postal Code
41009
Country
Spain
Individual Site Status
Recruiting
Facility Name
Beatson West of Scotland Cancer Centre
City
Glasgow
ZIP/Postal Code
G12 0YN
Country
United Kingdom
Individual Site Status
Completed
Facility Name
Barts Health NHS Trust - St Bartholomew's Hospital
City
London
ZIP/Postal Code
EC1A 7BE
Country
United Kingdom
Individual Site Status
Active, not recruiting

12. IPD Sharing Statement

Learn more about this trial

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

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