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

No Placebo-Only Group

Summary

This trial is testing the safety of abemaciclib when used with other treatments for patients whose breast cancer has spread. Abemaciclib helps to stop cancer cells from growing by blocking certain proteins they need. The study aims to find out if this combination is safe for patients with advanced breast cancer.

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.

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.

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

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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

Secondary study objectives

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

47%

Diarrhoea

33%

Fatigue

27%

Vomiting

27%

Asthenia

20%

Nausea

20%

Mucosal inflammation

20%

Decreased appetite

20%

Back pain

13%

Arthralgia

13%

Dysuria

13%

Rash

13%

Constipation

13%

Dry mouth

13%

Dizziness

13%

Neuropathy peripheral

13%

Dry skin

Spinal pain

Pruritus

Blood potassium decreased

Bronchitis

Localised oedema

Axillary pain

Chest pain

Erythema

Conjunctivitis

Muscle spasms

Neck pain

Dysaesthesia

Hypoaesthesia

Vulvovaginal discomfort

Vulvovaginal inflammation

Nail infection

Urinary tract infection

Pain

Gastrointestinal pain

Rhinitis

Abdominal pain

Herpes zoster

Weight decreased

Vulvovaginal dryness

Alopecia

Ejection fraction decreased

Depression

Ulcerative keratitis

Inflammation

Cognitive disorder

Dyspnoea

Oedema peripheral

Peripheral swelling

Burning sensation

Subclavian vein thrombosis

Erysipelas

100%

80%

60%

40%

20%

Study treatment Arm

Cohort 1 Doublet

Cohort 1 Triplet

Cohort 2

Awards & Highlights

No Placebo-Only Group

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

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

Everolimus

2010

Completed Phase 4

~1510

Trastuzumab

2014

Completed Phase 4

~5190

Letrozole

2002

Completed Phase 4

~3590

LY2835219

2014

Completed Phase 1

~80

Pertuzumab

2014

Completed Phase 3

~7500

Endocrine therapy

2019

Completed Phase 3

~35530

Loperamide

2010

Completed Phase 4

~2160

Anastrozole

2016

Completed Phase 4

~5550

Tamoxifen

2005

Completed Phase 4

~30110

Exemestane

2003

Completed Phase 4

~7510

LY3023414

2014

Completed Phase 2

~850

Fulvestrant

2011

Completed Phase 3

~3520

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.