Clinical Trial: NCT03280563 - My Cancer Genome

NCT03280563

Description:

This study is designed to evaluate the efficacy, safety, and pharmacokinetics of several immunotherapy-based combination treatments in participants with inoperable locally advanced or metastatic HR-positive, HER2-negative breast cancer who have progressed during or following treatment with a cyclin-dependent kinase (CDK) 4/6 inhibitor in the first- or second-line setting, such as palbociclib, ribociclib, or abemaciclib. The study will be performed in two stages. During Stage 1, participants will be randomized to fulvestrant (control) or an atezolizumab-containing doublet or triplet combination. Those who experience disease progression, loss of clinical benefit, or unacceptable toxicity may be eligible to receive a new triplet combination treatment in Stage 2 until loss of clinical benefit or unacceptable toxicity. New treatment arms may be added and/or existing treatment arms may be closed during the course of the study on the basis of ongoing clinical efficacy and safety as well as the current treatments available.

Related Conditions:

Invasive Breast Carcinoma

Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

URL:

https://clinicaltrials.gov/show/NCT03280563

Trial Eligibility

Document

Title

Brief Title: A Study of Multiple Immunotherapy-Based Treatment Combinations in Hormone Receptor (HR)-Positive Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer
Official Title: A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Hormone Receptor-Positive HER2-Negative Breast Cancer (MORPHEUS-HR+ Breast Cancer)

Clinical Trial IDs

ORG STUDY ID: CO39611
SECONDARY ID: 2017-000335-14
NCT ID: NCT03280563

Conditions

Breast Neoplasms

Interventions

Drug	Synonyms	Arms
Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody	Tecentriq	Stage 1: Atezolizumab + Abemaciclib + Fulvestrant
Bevacizumab	Avastin	Stage 2: Atezolizumab + Bevacizumab + Endocrine Therapy
Entinostat		Stage 1: Atezolizumab + Entinostat
Exemestane		Stage 2: Atezolizumab + Bevacizumab + Endocrine Therapy
Fulvestrant		Stage 1: Atezolizumab + Abemaciclib + Fulvestrant
Ipatasertib		Stage 1: Atezolizumab + Ipatasertib
Tamoxifen		Stage 2: Atezolizumab + Bevacizumab + Endocrine Therapy
Abemaciclib		Stage 1: Atezolizumab + Abemaciclib + Fulvestrant

Purpose

Trial Arms

Name	Type	Description	Interventions
Stage 1: Fulvestrant	Active Comparator	Participants will receive fulvestrant until unacceptable toxicity or disease progression according to RECIST v1.1.	Fulvestrant
Stage 1: Atezolizumab + Entinostat	Experimental	Participants will receive doublet combination treatment with atezolizumab plus entinostat until unacceptable toxicity or loss of clinical benefit as determined by the investigator.	Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody Entinostat
Stage 1: Atezolizumab + Fulvestrant	Experimental	Participants will receive doublet combination treatment with atezolizumab plus fulvestrant until unacceptable toxicity or loss of clinical benefit as determined by the investigator.	Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody Fulvestrant
Stage 1: Atezolizumab + Ipatasertib	Experimental	Participants will receive doublet combination treatment with atezolizumab plus ipatasertib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Prior to enrollment into this arm, the first 6 participants in the study will complete a safety run-in with atezolizumab plus ipatasertib.	Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody Ipatasertib
Stage 1: Atezolizumab + Ipatasertib + Fulvestrant	Experimental	Participants will receive triplet combination treatment with atezolizumab plus ipatasertib plus fulvestrant until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Prior to enrollment into this arm, the first 6 participants in the study will complete a safety run-in with atezolizumab plus ipatasertib.	Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody Fulvestrant Ipatasertib
Stage 2: Atezolizumab + Bevacizumab + Endocrine Therapy	Experimental	Those who progress or experience unacceptable toxicity during treatment in Stage 1 may be eligible to enter Stage 2. Participants will receive triplet combination therapy with atezolizumab plus bevacizumab plus one of three endocrine therapies (fulvestrant, exemestane, or tamoxifen) selected by the physician. Treatment in Stage 2 will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator.	Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody Bevacizumab Exemestane Fulvestrant Tamoxifen
Stage 1: Mandatory On-Treatment Biopsy	Experimental	For experimental combination arms that demonstrate clinical activity during the preliminary phase, the Sponsor may open enrollment into a separate mandatory on-treatment biopsy cohort for that combination.	Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody Entinostat Fulvestrant Ipatasertib Abemaciclib
Stage 1: Atezolizumab + Abemaciclib + Fulvestrant	Experimental	Participants will receive triplet combination treatment with atezolizumab plus abemaciclib plus fulvestrant until unacceptable toxicity or loss of clinical benefit as determined by the investigator.	Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody Fulvestrant Abemaciclib

Eligibility Criteria

        Inclusion Criteria for Both Stages:

          -  Measurable disease per RECIST v1.1

          -  Adequate hematologic and end organ function

          -  Disease progression during or after first- or second-line hormonal therapy with CDK4/6
             inhibitor

        Inclusion Criteria for Stage 1:

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  Metastatic or inoperable, locally advanced, histologically or cytologically confirmed
             invasive HR-positive HER2-negative breast cancer

          -  Recommended for endocrine therapy, and cytotoxic chemotherapy not indicated at study
             entry

          -  Recurrence or progression following most recent systemic breast cancer therapy

          -  Disease progression during or after first- or second-line hormonal therapy for locally
             advanced or metastatic disease

          -  Postmenopausal according to protocol-defined criteria

          -  Life expectancy >3 months

          -  Available tumor specimen for determination of PD-L1 status

        Inclusion Criteria for Stage 2:

          -  ECOG performance status of 0-2

          -  Ability to initiate treatment within 3 months after disease progression or
             unacceptable toxicity on a Stage 1 regimen

        Exclusion Criteria for Both Stages:

          -  Significant or uncontrolled comorbid disease as specified in the protocol

          -  Uncontrolled tumor-related pain

          -  Autoimmune disease except for stable/controlled hypothyroidism, Type 1 diabetes
             mellitus, or certain dermatologic conditions

          -  Positive human immunodeficiency virus test

          -  Active hepatitis B or C

          -  Active tuberculosis

          -  Severe infection within 4 weeks and/or antibiotics within 2 weeks prior to study
             treatment

          -  Prior allogeneic stem cell or solid organ transplantation

          -  History of malignancy other than breast cancer within 2 years prior to screening
             except those with negligible risk of metastasis/death

          -  History of or known hypersensitivity to study drug or excipients

          -  For patients entering Stage 2, recovery from all immunotherapy-related adverse events
             to Grade 1 or better or to baseline at the time of consent

        Exclusion Criteria for Stage 1:

          -  Prior fulvestrant or cytotoxic chemotherapy for metastatic breast cancer, or certain
             other agents as specified in the protocol

          -  Unresolved AEs from prior anti-cancer therapy

          -  Eligibility only for the control arm

          -  Prior treatment with inhibitors as specified in the protocol

        Exclusion Criteria for Stage 2:

          -  Unacceptable toxicity with atezolizumab during Stage 1

          -  Uncontrolled cardiovascular disease or coagulation disorder, including use of
             anticoagulants as specified in the protocol

          -  Significant abdominal or intestinal manifestations within 6 months prior to treatment

          -  Grade 2 or higher proteinuria

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	Female
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Percentage of Participants with Objective Response during Stage 1 According to Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
Time Frame:	From baseline until disease progression or loss of clinical benefit (up to 6 years overall)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:	Progression-Free Survival during Stage 1 According to RECIST v1.1
Time Frame:	From randomization until disease progression or death from any cause (up to 6 years overall)
Safety Issue:
Description:

Measure:	Percentage of Participants with Clinical Benefit during Stage 1 According to RECIST v1.1
Time Frame:	From baseline until disease progression or loss of clinical benefit (up to 6 years overall)
Safety Issue:
Description:

Measure:	Overall Survival during Stage 1
Time Frame:	From randomization until death from any cause (up to 6 years overall)
Safety Issue:
Description:

Measure:	Percentage of Participants Alive at 18 Months during Stage 1
Time Frame:	18 months
Safety Issue:
Description:

Measure:	Duration of Response during Stage 1 According to RECIST v1.1
Time Frame:	From first objective response until disease progression or death from any cause (up to 6 years overall)
Safety Issue:
Description:

Measure:	Percentage of Participants with Adverse Events (AEs) during Stage 1
Time Frame:	From baseline until 30 days after last dose or initiation of new systemic anti-cancer therapy (up to 6 years overall)
Safety Issue:
Description:

Measure:	Percentage of Participants with AEs during Stage 2
Time Frame:	From baseline until 30 days after last dose or initiation of new systemic anti-cancer therapy (up to 6 years overall)
Safety Issue:
Description:

Measure:	Atezolizumab Serum Concentration during Stage 1
Time Frame:	Predose (0 hours [h]) on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 (cycle = 21-28 days); postdose (30 min) (infusion = 30-60 min) on Day 1 of Cycle 1; at treatment discontinuation (up to 6 years); and 120 days after last dose (up to 6 years overall)
Safety Issue:
Description:

Measure:	Entinostat Serum and Plasma Concentration during Stage 1
Time Frame:	Serum predose (0 h) and plasma postdose (2-4 h) on Day 1 of Cycle 1; plasma predose (0 h) on Day 1 of Cycle 2 (cycle = 21 days)
Safety Issue:
Description:

Measure:	Fulvestrant Plasma Concentration during Stage 1
Time Frame:	Predose (0 h) on Day 1 of Cycles 2-3 (cycle = 28 days)
Safety Issue:
Description:

Measure:	Ipatasertib Plasma Concentration during Stage 1
Time Frame:	Predose (0 h) and postdose (1, 2, 4, 6 h) on Day 15 of Cycle 1; postdose (1-3 h) on Day 15 of Cycle 3
Safety Issue:
Description:

Measure:	Atezolizumab Serum Concentration during Stage 2
Time Frame:	Predose (0 h) on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 (cycle = 21-28 days); postdose (30 min) (infusion = 30-60 min) on Day 1 of Cycle 1; at treatment discontinuation (up to 6 years); and 120 days after last dose (up to 6 years overall)
Safety Issue:
Description:

Measure:	Bevacizumab Serum Concentration during Stage 2
Time Frame:	Predose (0 h) and postdose (30 min) (infusion = 30-90 min) on Day 1 of Cycles 1, 3 (cycle = 21-28 days); at treatment discontinuation (up to 6 years); and 120 days after last dose (up to 6 years overall)
Safety Issue:
Description:

Measure:	Exemestane Plasma Concentration during Stage 2
Time Frame:	Predose (0 h) on Day 1 of Cycle 2 (cycle = 21 days)
Safety Issue:
Description:

Measure:	Fulvestrant Plasma Concentration during Stage 2
Time Frame:	Predose (0 h) on Day 1 of Cycles 2-3 (cycle = 28 days)
Safety Issue:
Description:

Measure:	Tamoxifen Plasma Concentration during Stage 2
Time Frame:	Predose (0 h) on Day 1 of Cycle 2 (cycle = 21 days)
Safety Issue:
Description:

Measure:	Percentage of Participants with Anti-Drug Antibodies (ADAs) to Atezolizumab during Stage 1
Time Frame:	Predose (0 h) on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 (cycle = 28 days); at treatment discontinuation (up to 6 years); and 120 days after last dose (up to 6 years overall)
Safety Issue:
Description:

Measure:	Percentage of Participants with ADAs to Atezolizumab during Stage 2
Time Frame:	Predose (0 h) on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 (cycle = 21-28 days); at treatment discontinuation (up to 6 years); and 120 days after last dose (up to 6 years overall)
Safety Issue:
Description:

Measure:	Percentage of Participants with ADAs to Bevacizumab during Stage 2
Time Frame:	Predose (0 h) on Day 1 of Cycles 1, 3 (cycle = 21-28 days); at treatment discontinuation (up to 6 years); and 120 days after last dose (up to 6 years overall)
Safety Issue:
Description:

Measure:	Abemaciclib Plasma Concentration during Stage 1
Time Frame:	Predose (0 h), Postdose (30 minutes post infusion), and 4-8 hours after dose on Day 1 Cycle 1; Predose on Day 15 Cycle 1 and Day 1 of Cycles 2 and 3
Safety Issue:
Description:

Details

Phase:	Phase 1/Phase 2
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	Hoffmann-La Roche

Last Updated

August 6, 2021

Clinical Trials /

A Study of Multiple Immunotherapy-Based Treatment Combinations in Hormone Receptor (HR)-Positive Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer