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CDK 4/6 Inhibitor

Immunotherapy Combinations for Breast Cancer (MORPHEUS HR+BC Trial)

Phase 1 & 2

Waitlist Available

Research Sponsored by Hoffmann-La Roche

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Must not have

Prior allogeneic stem cell or solid organ transplantation

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing different combinations of immunotherapy drugs to see which are the most effective at treating HR-positive, HER2-negative breast cancer that has progressed after treatment with a CDK4/6 inhibitor.

Who is the study for?

This trial is for postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer that worsened after CDK4/6 inhibitor therapy. Participants should have measurable disease, a life expectancy over 3 months, and good organ function. They must not have severe recent illnesses, uncontrolled diseases, certain past cancers within 2 years (except low-risk types), or previous adverse reactions to the study drugs.

What is being tested?

The trial tests combinations of immunotherapies and hormone therapies like Fulvestrant and Exemestane with targeted treatments such as Ipatasertib in women whose breast cancer has progressed on CDK4/6 inhibitors. It's split into two stages: initial randomization to control or combination treatment; then possible new triplet combos if needed due to progression or side effects.

What are the potential side effects?

Potential side effects include immune-related inflammation in various organs, infusion reactions from antibody treatments like Atezolizumab, hormonal changes from drugs like Tamoxifen and Fulvestrant, liver issues from Ipatasertib, bleeding risks associated with Bevacizumab use, and general symptoms such as fatigue.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am fully active or can carry out light work.

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My breast cancer is advanced, cannot be removed by surgery, is HR-positive and HER2-negative.

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I am postmenopausal according to the study's criteria.

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I am advised to undergo hormone therapy, and chemotherapy is not recommended for me now.

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My breast cancer has returned or worsened after the latest treatment.

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My condition worsened despite hormonal therapy for advanced cancer.

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I am able to care for myself and perform daily activities.

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My cancer progressed despite hormone therapy and CDK4/6 inhibitor treatment.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had a previous transplant of stem cells or an organ.

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I have recovered from side effects of immunotherapy to my normal health or almost.

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I have received specific treatments for metastatic breast cancer as outlined in the protocol.

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I still have side effects from previous cancer treatments.

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I do not have uncontrolled heart disease or blood clotting disorders.

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I had severe side effects from atezolizumab in Stage 1.

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I have pain from my cancer that isn't relieved by treatment.

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I have active tuberculosis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Side effects data

From 2018 Phase 2 trial • 132 Patients • NCT02102490

91%

Diarrhoea

67%

Nausea

48%

Fatigue

45%

Decreased appetite

35%

Vomiting

27%

Anaemia

26%

Abdominal pain

23%

Asthenia

23%

Neutrophil count decreased

21%

Cough

20%

Constipation

20%

Headache

19%

Arthralgia

18%

White blood cell count decreased

18%

Neutropenia

15%

Alopecia

14%

Dry mouth

14%

Platelet count decreased

14%

Weight decreased

14%

Dysgeusia

13%

Dyspnoea

12%

Abdominal pain upper

12%

Back pain

12%

Dizziness

11%

Oedema peripheral

11%

Dyspepsia

11%

Pyrexia

11%

Blood creatinine increased

10%

Pain

Stomatitis

Aspartate aminotransferase increased

Thrombocytopenia

Lacrimation increased

Dehydration

Dry skin

Pruritus

Alanine aminotransferase increased

Flatulence

Upper respiratory tract infection

Urinary tract infection

Hypokalaemia

Chills

Musculoskeletal chest pain

Musculoskeletal pain

Anxiety

Gastrooesophageal reflux disease

Rash

Myalgia

Cellulitis

Pleural effusion

Atypical pneumonia

Gastroenteritis viral

Lung infection

Sepsis

Fall

Hip fracture

Pneumonitis

Pneumothorax

Febrile neutropenia

Respiratory tract infection

Haematotoxicity

Sinus bradycardia

Tachycardia

Large intestinal obstruction

Pancreatic enzyme abnormality

Pancreatitis

Varices oesophageal

Electrocardiogram abnormal

Liver function test abnormal

Renal function test abnormal

Bone pain

Muscular weakness

Acute kidney injury

Pulmonary embolism

Arterial thrombosis

Epilepsy

100%

80%

60%

40%

20%

Study treatment Arm

Abemaciclib

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

8Treatment groups

Experimental Treatment

Active Control

Group I: Stage 2: Atezolizumab + Bevacizumab + Endocrine TherapyExperimental Treatment5 Interventions

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.

Group II: Stage 1: Mandatory On-Treatment BiopsyExperimental Treatment5 Interventions

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.

Group III: Stage 1: Atezolizumab + Ipatasertib + FulvestrantExperimental Treatment3 Interventions

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.

Group IV: Stage 1: Atezolizumab + IpatasertibExperimental Treatment2 Interventions

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.

Group V: Stage 1: Atezolizumab + FulvestrantExperimental Treatment2 Interventions

Participants will receive doublet combination treatment with atezolizumab plus fulvestrant until unacceptable toxicity or loss of clinical benefit as determined by the investigator.

Group VI: Stage 1: Atezolizumab + EntinostatExperimental Treatment2 Interventions

Participants will receive doublet combination treatment with atezolizumab plus entinostat until unacceptable toxicity or loss of clinical benefit as determined by the investigator.

Group VII: Stage 1: Atezolizumab + Abemaciclib + FulvestrantExperimental Treatment3 Interventions

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.

Group VIII: Stage 1: FulvestrantActive Control1 Intervention

Participants will receive fulvestrant until unacceptable toxicity or disease progression according to RECIST v1.1.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Fulvestrant

2011

Completed Phase 3

~3520

Exemestane

2003