Lenvatinib + Pembrolizumab for Breast Cancer

Overseen By Oana Danciu

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: University of Illinois at Chicago

Must not be taking: Investigational drugs

Disqualifiers: Active infection, Pregnancy, Prior treatment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 5

Duration: 1 week

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the effectiveness of combining lenvatinib (a targeted therapy) and pembrolizumab (an immunotherapy) for individuals with triple-negative breast cancer (TNBC). Participants will receive these medications before surgery to determine if this combination improves surgical outcomes. Suitable candidates have TNBC and are planning surgery to attempt a cure. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this combination therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the combination of lenvatinib and pembrolizumab has been tested in patients with various types of cancer, including advanced stages. Studies have found that the treatment has a manageable safety profile, meaning most side effects can be treated with proper care. In one study, more serious side effects, known as grade 3 or 4, occurred in a significant number of patients. These severe reactions are common in cancer treatments.

Despite the occurrence of some serious side effects, the treatment's safety remains manageable for many patients. It is important to note that this information comes from studies involving patients with advanced cancers, where risks might differ compared to earlier stages.

Prospective trial participants should discuss these findings with a healthcare professional to make an informed decision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Researchers are excited about the combination of Lenvatinib and Pembrolizumab for breast cancer because it offers a novel approach compared to current treatments. Most standard treatments for breast cancer, like chemotherapy and hormone therapy, target cancer cells directly or block hormones that fuel cancer growth. But this combination works differently; Lenvatinib is a targeted therapy that inhibits growth factors involved in tumor development, while Pembrolizumab is an immunotherapy that helps the immune system recognize and attack cancer cells. This dual approach has the potential to enhance the body's natural defenses against cancer, offering hope for improved outcomes.

What evidence suggests that this treatment might be an effective treatment for breast cancer?

Previous studies have shown promising results with the combination of lenvatinib and pembrolizumab. Research indicates that this pair significantly improves survival rates in patients with advanced cancers compared to standard chemotherapy. Specifically, the studies reported a notable increase in tumor response, with 30.3% of patients experiencing tumor shrinkage or disappearance. In this trial, all participants will receive the lenvatinib and pembrolizumab combination, which shows meaningful potential in combating difficult cancers. ^{2 6 7 8 9}

Who Is on the Research Team?

Oana Danciu

Principal Investigator

University of Illinois at Chicago

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

I am eligible for surgery aimed at curing my condition.

Women of childbearing potential (WOCP) must not be pregnant or breast-feeding. A negative serum or urine pregnancy test is required within 14 days of study registration

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

Exclusion Criteria

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

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

I haven't taken lenvatinib or immune checkpoint inhibitors in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

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

1 week

1 visit (in-person)

Surgery

Participants undergo curative surgery 7-10 days after the last dose of lenvatinib

1-2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

2 visits (in-person)

Long-term Follow-up

Evaluate quality of life and effectiveness of treatment over an extended period

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Lenvatinib
• Pembrolizumab

Trial Overview 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.

How Is the Trial Designed?

Group I: Open Label Experimental Treatment 2 Interventions

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

Lenvatinib is already approved in United States, European Union for the following indications:

Approved in United States as Lenvima for:

• Differentiated Thyroid Cancer
• Renal Cell Carcinoma
• Hepatocellular Carcinoma
• Endometrial Cancer

Approved in European Union as Lenvima for:

• Thyroid Cancer
• Renal Cell Carcinoma
• Hepatocellular Carcinoma
• Endometrial Cancer

Approved in European Union as Kisplyx for:

• Renal Cell Carcinoma

Who Is Running the Clinical Trial?

University of Illinois at Chicago

Lead Sponsor

Trials

653

Recruited

1,574,000+

Published Research Related to This Trial

Combination therapy with pembrolizumab and lenvatinib is effective as a first-line treatment for clear cell renal carcinoma and as a second-line option for recurrent or metastatic endometrial carcinoma, based on data from five completed clinical trials and two ongoing trials.

This non-chemotherapy regimen helps spare patients from prolonged myelosuppression and lowers the risk of infection, making it a safer alternative for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined use of pembrolizumab and lenvatinib: A review. Eisinger, C., Muluneh, B.[2023]

In a phase 3 trial with 1069 patients, the combination of lenvatinib and pembrolizumab significantly improved progression-free survival compared to sunitinib, with a median of 23.9 months versus 9.2 months, indicating a strong efficacy of this regimen.

Lenvatinib plus pembrolizumab also resulted in longer overall survival compared to sunitinib, while the combination of lenvatinib and everolimus did not show a survival advantage over sunitinib. However, both lenvatinib combinations had a high incidence of grade 3 or higher adverse events, similar to sunitinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. Motzer, R., Alekseev, B., Rha, SY., et al.[2022]

In a phase 2 trial involving 29 patients with advanced gastric cancer, the combination of lenvatinib and pembrolizumab resulted in a promising objective response rate of 69%, indicating significant anti-tumor activity.

The treatment was generally well-tolerated, with the most common grade 3 adverse events being manageable, such as hypertension and proteinuria, and no serious treatment-related complications or deaths reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib plus pembrolizumab in patients with advanced gastric cancer in the first-line or second-line setting (EPOC1706): an open-label, single-arm, phase 2 trial. Kawazoe, A., Fukuoka, S., Nakamura, Y., et al.[2020]

The combination of pembrolizumab and lenvatinib has shown promising efficacy in treating advanced endometrial cancer, with previous trials indicating improved objective response rates and survival outcomes compared to standard chemotherapy.

This ongoing phase 3 trial aims to determine if pembrolizumab plus lenvatinib is superior to the chemotherapy regimen of paclitaxel plus carboplatin in newly diagnosed patients, with a target enrollment of about 875 participants and results expected in 2022.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 3, randomized, open-label study of pembrolizumab plus lenvatinib versus chemotherapy for first-line treatment of advanced or recurrent endometrial cancer: ENGOT-en9/LEAP-001. Marth, C., Tarnawski, R., Tyulyandina, A., et al.[2022]

In a phase 2 study involving 54 patients with advanced endometrial cancer, the combination of lenvatinib and pembrolizumab resulted in a 39.6% objective response rate at week 24, indicating significant anti-tumor activity.

The treatment was generally well-tolerated, with serious adverse events occurring in 30% of patients, including one treatment-related death; however, the safety profile was consistent with previous studies of the individual drugs, except for a higher incidence of hypothyroidism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial. Makker, V., Rasco, D., Vogelzang, NJ., et al.[2020]

In the CLEAR study involving 352 patients, the combination of lenvatinib and pembrolizumab showed a manageable safety profile, with common adverse reactions including fatigue (63.1%), diarrhea (61.9%), and hypertension (56.3%).

Most adverse reactions occurred within approximately 5 months of starting treatment, and effective management strategies such as monitoring and dose modifications were identified to ensure patient safety and support ongoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization and Management of Adverse Reactions From the CLEAR Study in Advanced Renal Cell Carcinoma Treated With Lenvatinib Plus Pembrolizumab. Motzer, R., George, S., Merchan, JR., et al.[2023]

In a phase 2 study involving 38 patients with pleural mesothelioma, the combination of pembrolizumab and lenvatinib resulted in a promising objective response rate of 58%, indicating significant anti-tumor activity after prior chemotherapy.

However, the treatment was associated with considerable toxicity, with 26% of patients experiencing serious treatment-related adverse events, including one death, highlighting the need for careful monitoring and supportive care during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus lenvatinib in second-line and third-line patients with pleural mesothelioma (PEMMELA): a single-arm phase 2 study. Douma, LH., Lalezari, F., van der Noort, V., et al.[2023]

The combination of lenvatinib and pembrolizumab shows significant clinical benefits for patients with endometrial carcinoma, with a safety profile consistent with each drug's individual use, primarily involving manageable side effects like hypertension and hypothyroidism.

Effective management of lenvatinib's common adverse events is crucial to maximize its efficacy, as most side effects can be prevented or mitigated through proactive monitoring and intervention during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma. Lorusso, D., Danesi, R., Locati, LD., et al.[2023]

In a study of 43 patients with recurrent endometrial cancer treated with lenvatinib and pembrolizumab, 84% experienced significant adverse events (AEs), with hypertension and weight loss being the most common.

Patients starting on a reduced dose of lenvatinib (10 mg or 14 mg) had significantly longer progression-free survival compared to those on the standard dose (20 mg), suggesting that dose optimization may improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events and oncologic outcomes with combination lenvatinib and pembrolizumab for the treatment of recurrent endometrial cancer. Zammarrelli, WA., Ma, W., Espino, K., et al.[2023]

In a phase 3 study involving 487 patients with advanced urothelial carcinoma, the combination of pembrolizumab and lenvatinib did not show improved progression-free survival (4.5 months) or overall survival (11.8 months) compared to pembrolizumab with placebo.

The combination treatment resulted in a higher rate of severe adverse events (51%) compared to the placebo group (27%), leading to the conclusion that the benefit-to-risk ratio was not favorable for using lenvatinib with pembrolizumab as first-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab with or Without Lenvatinib as First-line Therapy for Patients with Advanced Urothelial Carcinoma (LEAP-011): A Phase 3, Randomized, Double-Blind Trial. Matsubara, N., de Wit, R., Balar, AV., et al.[2023]

Citations

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KEYTRUDA® (pembrolizumab) Plus LENVIMA® ... KEYTRUDA® (pembrolizumab) Plus LENVIMA® (lenvatinib) Combination Demonstrated Statistically Significant Improvement in Overall Survival, ...

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NCT03797326 | Efficacy and Safety of Pembrolizumab (MK ... The purpose of this study is to determine the safety and efficacy of combination therapy with pembrolizumab (MK-3475) and lenvatinib (E7080/MK-7902) in ...

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First-Line Lenvatinib Plus Pembrolizumab Versus ... Grade 3 to 4 treatment-related AEs occurred in 321 patients (76%) and 272 patients (66%), respectively. Grade 5 AEs are summarized in the Data ...