What side effects are associated with this type of intervention?

Common treatments for breast cancer, particularly those involving CDK4/6 inhibitors like Abemaciclib, often include side effects such as neutropenia, diarrhea, fatigue, nausea, and infections. When combined with endocrine therapies (e.g., letrozole, anastrozole, tamoxifen), additional side effects may include hot flashes, joint pain, and bone thinning. Targeted therapies like trastuzumab can cause cardiac issues and infusion-related reactions. Overall, the side effects are generally manageable but require monitoring and supportive care.

What prior FDA approvals exist?

The FDA has approved several CDK4/6 inhibitors for the treatment of breast cancer, similar to Abemaciclib. These include Palbociclib (Ibrance), Ribociclib (Kisqali), and Abemaciclib (Verzenio) itself. These drugs are typically used in combination with endocrine therapies such as letrozole, anastrozole, or fulvestrant for the treatment of hormone receptor-positive, HER2-negative advanced or metastatic breast cancer. These combinations have shown to improve progression-free survival in patients.

What other types of research exist?

Promising novel alternatives to Abemaciclib for breast cancer patients include: 1) Ribociclib and Palbociclib, which are other CDK4/6 inhibitors. 2) Alpelisib, a PI3K inhibitor, particularly for patients with PIK3CA mutations. 3) Trastuzumab deruxtecan, an antibody-drug conjugate for HER2-positive breast cancer. 4) Pembrolizumab, an immune checkpoint inhibitor, especially for triple-negative breast cancer. These alternatives have shown efficacy in various clinical trials and may be considered based on individual patient profiles and specific cancer characteristics.

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CDK4/6 Inhibitor

Abemaciclib Combination Therapy for Advanced Breast Cancer

Phase 1

Waitlist Available

Research Sponsored by Eli Lilly and Company

Eligibility Criteria Checklist

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

Must have

For Part I (abemaciclib + endocrine therapy): The participant must have demonstrated evidence of disease progression on a Cyclin Dependent Kinase 4 (CDK4) and Cyclin Dependent Kinase 6 (CDK6) inhibitor (either palbociclib or ribociclib) plus endocrine therapy for advanced or metastatic disease as the most recent therapy immediately preceding study entry. The participant should remain on the current endocrine therapy while receiving abemaciclib

For Part A (LY2835219 + letrozole): Except for ongoing therapy with letrozole, the participant must not have received prior systemic endocrine therapy for metastatic disease

Must not have

Have brain metastasis without prior radiotherapy

For Parts F and H: Cardiac disease including myocardial infarction within 6 months, unstable angina, or New York Heart Association (NYHA) Grade II or greater functional impairment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline to study completion (estimated as 12 months)

Awards & highlights

Summary

This trial looks at the safety of using abemaciclib in different combinations of drugs to treat breast cancer that has spread.

Who is the study for?

This trial is for adults with breast cancer that has spread, who have specific treatment histories and organ function. Participants must not have severe preexisting conditions or certain heart diseases, and should not have received some treatments like CDK4/6 inhibitors (except in Part I) or systemic chemotherapy for metastatic disease.Check my eligibility

What is being tested?

The study tests the safety of abemaciclib combined with various therapies (like letrozole, anastrozole, tamoxifen) for advanced breast cancer. It examines how well these combinations work when the cancer has spread to other body parts.See study design

What are the potential side effects?

Potential side effects may include digestive issues, fatigue, blood disorders, liver problems, risk of infection due to immune system suppression. Specific side effects depend on the combination therapy used.

Eligibility Criteria

Inclusion Criteria

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

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

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I have not had hormone therapy for my cancer, except for letrozole.

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I am willing to have tumor biopsies before and after the study treatment.

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I am fully active and can carry on all pre-disease activities without restriction.

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I stopped all breast cancer treatments 21 days ago, except for hair loss or nerve issues.

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My blood, liver, and kidney functions are all within normal ranges.

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I am post-menopausal or pre-menopausal using ovarian suppression treatment.

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My breast cancer is HR+ and HER2-.

Exclusion Criteria

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

Select...

I have cancer that has spread to my brain and haven't had brain radiation.

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I have not had a heart attack or severe heart issues in the last 6 months.

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My breast cancer has spread, is worsening quickly, and is affecting my organs.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline to study completion (estimated as 12 months)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline to study completion (estimated as 12 months)

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline to study completion (estimated as 12 months) for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Number of Participants with One or More Drug-Related Adverse Events

Secondary outcome measures

Change in MD Anderson Symptom Inventory (MDASI) Score from Baseline

Number of Participants with a Complete or Partial Tumor Response (Overall Response Rate)

Pharmacokinetics: Area under the Curve (AUC) of LY2835219, Letrozole, Anastrozole, Tamoxifen, Exemestane, Everolimus, Trastuzumab, LY3023414, Fulvestrant, and Pertuzumab

+2 more

Side effects data

From 2023 Phase 2 trial • 105 Patients • NCT03321981

72%

Diarrhoea

46%

Asthenia

46%

Nausea

44%

Neutropenia

33%

Fatigue

31%

Constipation

28%

Anaemia

23%

Abdominal pain

18%

Neutrophil count decreased

18%

Cough

18%

Headache

18%

Weight decreased

15%

Muscle spasms

15%

Vomiting

15%

Urinary tract infection

15%

Decreased appetite

15%

Neuropathy peripheral

15%

Dyspnoea

13%

Pyrexia

13%

Myalgia

13%

Alopecia

10%

Blood potassium decreased

10%

Stomatitis

10%

Dysgeusia

10%

Chest pain

Back pain

Oedema peripheral

Ejection fraction decreased

Mucosal inflammation

Depression

Pruritus

Epistaxis

Aspartate aminotransferase increased

Arthralgia

Dysphagia

Insomnia

Tinnitus

Dry eye

Non-cardiac chest pain

Paronychia

Pain in jaw

Peripheral motor neuropathy

Thrombocytopenia

Gastrointestinal pain

Gastrooesophageal reflux disease

Nasopharyngitis

Chills

Pain in extremity

Dizziness

Paraesthesia

Platelet count decreased

Hot flush

Influenza

Neuralgia

Peripheral sensory neuropathy

Urinary incontinence

Pain

Infusion related reaction

Skin fissures

Erysipelas

Enthesopathy

Dehydration

Photophobia

Oesophageal pain

Rectal haemorrhage

Leukopenia

Aphthous ulcer

Eyelid sensory disorder

Tachycardia

Gait disturbance

Osteomyelitis

Abscess limb

Upper respiratory tract infection

Humerus fracture

Mobility decreased

Muscular weakness

Onycholysis

Febrile neutropenia

Blepharitis

Ulcerative keratitis

Gastritis

Rash pustular

Sciatica

Somnolence

Telangiectasia

Toothache

Chalazion

Haemorrhoids

Sepsis

Seizure

Eye allergy

Hypoaesthesia oral

Breast inflammation

Hyperthermia

Rash

Malabsorption

Hypersensitivity

Lung infection

Pharyngitis

Skin infection

Alanine aminotransferase increased

Blood calcium decreased

Blood phosphorus decreased

Blood sodium decreased

Body temperature increased

Abdominal pain upper

Mastitis fungal

Oral fungal infection

Stress urinary incontinence

Haemoptysis

Skin ulcer

Aphasia

Orthostatic hypotension

Nervous system disorder

Restless legs syndrome

Vocal cord paralysis

Stress

Breast pain

Nasal congestion

Sinusitis

Iron deficiency

Anxiety

Nail disorder

Rhinorrhoea

Erythema

Rash maculo-papular

Hypotension

Visual acuity reduced

Abdominal distension

Colitis

Oral candidiasis

Foot fracture

Procedural dizziness

Amnesia

Nail discolouration

Vertigo

Localised oedema

100%

80%

60%

40%

20%

Study treatment Arm

Cohort 1 Triplet

Cohort 1 Doublet

Cohort 2

Trial Design

13Treatment groups

Experimental Treatment

Group I: LY3023414 + LY2835219 + Fulvestrant Dose ExpansionExperimental Treatment3 Interventions

LY3023414 administered orally. LY2835219 administered orally. Fulvestrant administered IM.

Group II: LY3023414 + LY2835219 + Fulvestrant Dose EscalationExperimental Treatment3 Interventions

LY3023414 administered orally. LY2835219 administered orally. Fulvestrant administered intramuscularly (IM).

Group III: LY2835219+ Trastuzumab Dose ExpansionExperimental Treatment2 Interventions

LY2835219 administered orally. Trastuzumab administered IV infusion. This arm is closed to enrollment.

Group IV: LY2835219+ Trastuzumab Dose EscalationExperimental Treatment2 Interventions

LY2835219 administered orally. Trastuzumab administered intravenously (IV) infusion. This arm is closed to enrollment.

Group V: LY2835219 +Trastuzumab +Pertuzumab +Loperamide Dose EscalationExperimental Treatment4 Interventions

LY2835219 administered orally. Loperamide administered orally. Trastuzumab administered IV infusion. Pertuzumab administered IV infusion.

Group VI: LY2835219 +Trastuzumab + Pertuzumab +Loperamide Dose ExpansionExperimental Treatment5 Interventions

Hormone Receptor Negative (HR-): LY2835219 administered orally. Loperamide administered orally. Trastuzumab administered IV infusion. Pertuzumab administered IV infusion. Hormone Receptor Positive (HR+): LY2835219 administered orally. Loperamide administered orally. Trastuzumab administered IV infusion. Pertuzumab administered IV infusion. Endocrine therapy administered orally.

Group VII: LY2835219 + TamoxifenExperimental Treatment2 Interventions

LY2835219 administered orally. Tamoxifen administered orally. This arm is closed to enrollment.

Group VIII: LY2835219 + LetrozoleExperimental Treatment2 Interventions

LY2835219 administered orally. Letrozole administered orally. This arm is closed to enrollment.

Group IX: LY2835219 + Exemestane + Everolimus Dose ExpansionExperimental Treatment3 Interventions

LY2835219 administered orally. Exemestane administered orally. Everolimus administered orally. This arm is closed to enrollment.

Group X: LY2835219 + Exemestane + Everolimus Dose EscalationExperimental Treatment3 Interventions

LY2835219 administered orally. Exemestane administered orally. Everolimus administered orally. This arm is closed to enrollment.

Group XI: LY2835219 + ExemestaneExperimental Treatment2 Interventions

LY2835219 administered orally. Exemestane administered orally. This arm is closed to enrollment.

Group XII: LY2835219 + Endocrine TherapyExperimental Treatment2 Interventions

LY2835219 administered orally. Ongoing endocrine therapy administered orally.

Group XIII: LY2835219 + AnastrozoleExperimental Treatment2 Interventions

LY2835219 administered orally. Anastrozole administered orally. This arm is closed to enrollment.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Exemestane

2003

Completed Phase 4

~7630

LY2835219

2009

Completed Phase 1

~300

Tamoxifen

2005

Completed Phase 4

~30070

Anastrozole

2019

Completed Phase 4

~6260

LY3023414

2014

Completed Phase 2

~850

Fulvestrant

2011

Completed Phase 3

~3810

Pertuzumab

2014

Completed Phase 3

~7500

Loperamide

2010

Completed Phase 4

~2160

Trastuzumab

2014

Completed Phase 4

~5190

Everolimus

2010

Completed Phase 4

~1510

Endocrine therapy

2019

Completed Phase 3

~35530

Letrozole

2002

Completed Phase 4

~2810

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

CDK4/6 inhibitors, such as Abemaciclib, work by blocking the activity of cyclin-dependent kinases 4 and 6, which are crucial for cell cycle progression and cancer cell proliferation. This inhibition helps to halt the growth of cancer cells. Aromatase inhibitors like letrozole and anastrozole reduce estrogen levels by blocking the enzyme aromatase, which converts androgens to estrogens, thereby slowing the growth of hormone receptor-positive breast cancer. Tamoxifen, a selective estrogen receptor modulator, binds to estrogen receptors on cancer cells, preventing estrogen from stimulating cancer growth. Exemestane, another aromatase inhibitor, works similarly by reducing estrogen production. These treatments are vital for breast cancer patients as they target specific pathways involved in cancer cell growth and proliferation, offering more personalized and effective treatment options.

The role of abemaciclib in treatment of advanced breast cancer.