What side effects are associated with this type of intervention?

Common side effects of breast cancer treatments similar to Lenvatinib and Pembrolizumab include hypertension, proteinuria, diarrhea, fatigue, and hand-foot syndrome for Tyrosine Kinase Inhibitors like Lenvatinib. For PD-1 inhibitors like Pembrolizumab, immune-related adverse events such as pneumonitis, colitis, hepatitis, endocrinopathies (e.g., thyroid dysfunction), and skin reactions are common. Severe adverse effects, though less frequent, can include severe pneumonitis and colitis.

What prior FDA approvals exist?

The FDA has approved several treatments for breast cancer that involve tyrosine kinase inhibitors (TKIs) and PD-1 inhibitors. Pembrolizumab, a PD-1 inhibitor, has been approved for use in combination with chemotherapy for patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1. While lenvatinib, a TKI, is not specifically approved for breast cancer, other TKIs like lapatinib and neratinib have been approved for HER2-positive breast cancer. These treatments target specific pathways to inhibit cancer growth and improve patient outcomes.

What other types of research exist?

Promising novel alternatives for breast cancer treatment in 2024 include: 1) Sacituzumab Govitecan, an antibody-drug conjugate targeting Trop-2, which has shown efficacy in triple-negative breast cancer. 2) Trastuzumab Deruxtecan, another antibody-drug conjugate targeting HER2, effective in HER2-positive breast cancer. 3) Alpelisib, a PI3K inhibitor, used in combination with endocrine therapy for HR-positive, HER2-negative breast cancer with PIK3CA mutations. 4) Atezolizumab, a PD-L1 inhibitor, which can be combined with nab-paclitaxel for PD-L1-positive triple-negative breast cancer.

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Tyrosine Kinase Inhibitor

Lenvatinib + Pembrolizumab for Breast Cancer

Phase 1

Recruiting

Led By Oana Danciu, MD

Research Sponsored by University of Illinois at Chicago

Eligibility Criteria Checklist

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

Must have

Must be candidates for curative surgical resection

Histologically confirmed invasive breast carcinoma documented by core needle biopsy or incisional biopsy (excisional biopsy is not allowed). AJCC 8th edition clinical stage T1b-T3/N0-N3/M0 by physical exam or radiologic studies

Must not have

Known history of AIDS (HIV testing is not mandatory). HIV-positive individuals on active HARRT therapy with virologic suppression (defined as an HIV-1 RNA level below the lower limit of detection of the assay used) within 90 days of study enrollment and a CD4 cell count >500 cells/mm3 on the most recent determination are eligible for the study

Any mental or medical condition that prevents the patient from giving informed consent or participating in the trial

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial involves patients with untreated triple negative breast cancer who will take a pill called Lenvatinib and receive an IV drug called Pembrolizumab. Lenvatinib helps stop the tumor from growing by cutting off its blood supply, and Pembrolizumab helps the immune system attack the cancer.

Who is the study for?

This trial is for adults with early-stage triple-negative breast cancer (TNBC) who haven't had previous cancer treatments and are planning surgery. They must have good performance status, no distant metastases, adequate organ function, and not be pregnant or breastfeeding. Participants should agree to use effective birth control and be able to follow study procedures.

What is being tested?

The trial tests Lenvatinib taken daily for a week plus one dose of Pembrolizumab given intravenously before surgery. It's designed to see if this combination can benefit patients with TNBC when administered preoperatively in those awaiting surgical tumor removal.

What are the potential side effects?

Lenvatinib may cause high blood pressure, fatigue, diarrhea, decreased appetite, weight loss, nausea, inflammation of mucous membranes and proteinuria. Pembrolizumab could lead to immune-related side effects like inflammation in various organs including the lungs or intestines.

Eligibility Criteria

Inclusion Criteria

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

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I am eligible for surgery aimed at curing my condition.

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My breast cancer was confirmed by a biopsy and is at a certain stage according to specific criteria.

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My cancer has not spread to distant parts of my body.

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My breast cancer is triple-negative.

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I have a biopsy sample available for analysis.

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I am 18 years old or older.

Exclusion Criteria

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

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I am HIV positive, on effective treatment, with undetectable virus levels and a high CD4 count.

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I am mentally and physically capable of participating in a clinical trial.

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I have not had a stroke or mini-stroke in the last 6 months.

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I have severe heart failure or my heart's pumping ability is below 50%.

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I have had treatments like chemotherapy or radiation for my current breast cancer.

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I am currently on medication for an infection.

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I do not have serious heart rhythm problems, or if I do, I have a pacemaker.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~5 years

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

Treatment Details

Study Objectives

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

Primary study objectives

Evaluate the effectiveness of preoperative anti-vascular endothelial growth factor receptor (VEGFR) therapy and immune checkpoint blockade on infiltration of CD8+ tumor infiltrating lymphocytes (TILs) (CD45RA-/CD8+/FoxP3-) in primary tumors from patients

Secondary study objectives

Evaluate clinical response to preoperative anti-VEGFR therapy and immune checkpoint blockade based on pathologic complete response and residual tumor burden in subjects receiving neoadjuvant chemotherapy and changes in the Ki-67 index in all patients.

Evaluate treatment tolerability of preoperative anti-VEGFR therapy and immune checkpoint blockade assessed by failure to completed planned course of neoadjuvant chemo-immune therapy and surgery in patients with early-stage TNBC

Other study objectives

Evaluate quality of life in patients with early-stage TNBC treated with preoperative anti-VEGFR therapy and immune checkpoint blockade

Side effects data

From 2024 Phase 3 trial • 804 Patients • NCT03040999

64%

Radiation skin injury

63%

Stomatitis

58%

Anaemia

56%

Nausea

48%

Dry mouth

45%

Constipation

45%

Weight decreased

44%

Dysphagia

42%

Neutrophil count decreased

33%

Dysgeusia

33%

Vomiting

32%

Fatigue

31%

White blood cell count decreased

28%

Hypomagnesaemia

26%

Decreased appetite

25%

Hypothyroidism

25%

Hypokalaemia

24%

Lymphocyte count decreased

24%

Platelet count decreased

23%

Oropharyngeal pain

23%

Blood creatinine increased

22%

Diarrhoea

22%

Odynophagia

20%

Hypoacusis

20%

Alanine aminotransferase increased

20%

Hyponatraemia

19%

Tinnitus

19%

Oral candidiasis

19%

Asthenia

16%

Pyrexia

16%

Cough

15%

Aspartate aminotransferase increased

15%

Rash

14%

Insomnia

13%

Acute kidney injury

13%

Pharyngeal inflammation

13%

Pruritus

12%

Dysphonia

12%

Gamma-glutamyltransferase increased

11%

Pneumonia

11%

Dehydration

10%

Hyperthyroidism

10%

Hypoalbuminaemia

10%

Hypocalcaemia

10%

Headache

10%

Productive cough

Neck pain

Peripheral sensory neuropathy

Gastrooesophageal reflux disease

Hiccups

Hyperglycaemia

Hyperuricaemia

Dizziness

Hypophosphataemia

Urinary tract infection

Ear pain

Localised oedema

Hyperkalaemia

Erythema

Oral pain

Abdominal pain upper

Arthralgia

Anxiety

Febrile neutropenia

Dyspepsia

Saliva altered

Back pain

Oedema peripheral

Hypertension

Dyspnoea

Nasopharyngitis

Alopecia

Dry skin

Sepsis

Pneumonia aspiration

Trismus

Pneumonitis

Laryngeal oedema

Malnutrition

Pharyngeal haemorrhage

Cellulitis

Septic shock

Systemic infection

Clostridium difficile colitis

Cardiac arrest

Death

Bronchitis

Hepatitis

Immune-mediated hepatitis

Oesophagitis

General physical health deterioration

Hypophagia

Tumour haemorrhage

Cerebrovascular accident

Syncope

Acute respiratory failure

Aspiration

Colitis

Mouth haemorrhage

Hypersensitivity

Acute myocardial infarction

Abscess neck

Device related infection

Stoma site infection

Vascular device infection

Wound infection

Hypercalcaemia

Pulmonary embolism

Respiratory failure

100%

80%

60%

40%

20%

Study treatment Arm

Placebo + CRT Followed by Placebo

Pembrolizumab + CRT Followed by Pembrolizumab

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Open LabelExperimental Treatment2 Interventions

All participants will receive lenvatinib 12mg daily for 7 days and pembrolizumab 200 mg IV on day 1 prior to surgery

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

2017

Completed Phase 3

~3150

Lenvatinib

2017

Completed Phase 4

~2070

0 / 13Eligibility 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

Lenvatinib, a tyrosine kinase inhibitor, blocks enzymes involved in cancer cell growth and angiogenesis, while Pembrolizumab, a PD-1 inhibitor, enhances the immune system's ability to detect and destroy cancer cells. These mechanisms are crucial for breast cancer patients as they help in selecting targeted therapies that can effectively inhibit tumor growth and improve immune response, potentially leading to better treatment outcomes.