Lenvatinib + Pembrolizumab for Salivary Gland Cancer

Recruiting at 11 trial locations

Overseen By David G. Pfister, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Steroids, Immunosuppressants, PD-1/PD-L1

Disqualifiers: Brain metastases, Hypertension, Autoimmune disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 3

Duration: 2 years

64 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications, but it does require a 4-week period since the end of any prior systemic treatment before starting the study drugs. It's best to discuss your current medications with the trial team to ensure they don't interfere with the study.

What data supports the effectiveness of the drug combination Lenvatinib and Pembrolizumab for treating salivary gland cancer?

Research shows that the combination of Lenvatinib and Pembrolizumab has demonstrated strong anti-tumor activity and lasting responses in various solid tumors, including endometrial and gastric cancers. This suggests potential effectiveness for other solid tumors like salivary gland cancer. ^{1 2 3 4 5}

Is the combination of Lenvatinib and Pembrolizumab safe for humans?

The combination of Lenvatinib and Pembrolizumab has been studied in various cancers and is generally considered safe, but it can cause side effects like high blood pressure, low thyroid function, diarrhea, nausea, vomiting, loss of appetite, fatigue, and weight loss. In some cases, it may also cause esophagitis (inflammation of the esophagus), which can lead to difficulty swallowing. ^{2 5 6 7 8}

How is the drug combination of lenvatinib and pembrolizumab unique for treating salivary gland cancer?

The combination of lenvatinib and pembrolizumab is unique because it targets both the blood vessels that supply the tumor and the immune system's ability to fight cancer, potentially offering a new option for salivary gland cancer, which currently has limited treatment options. ^{2 3 4 9 10}

What is the purpose of this trial?

This trial is testing lenvatinib and pembrolizumab in patients with advanced Adenoid Cystic Carcinoma or other salivary gland cancers that have come back or spread. Lenvatinib stops cancer cells from growing, while pembrolizumab helps the immune system attack the cancer. Researchers aim to see if these drugs are effective and safe for these patients. Lenvatinib and pembrolizumab have shown promising results in treating various advanced cancers, including thyroid, liver, endometrial, and gastric cancers.

Research Team

Alan L Ho, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults with advanced Adenoid Cystic Carcinoma or other salivary gland cancers that have returned or spread, who've had no recent treatments causing unresolved side effects. They must be able to swallow pills (or have a G-tube), not be pregnant or breastfeeding, and agree to use contraception. Participants need measurable disease and available tumor tissue for study.

Inclusion Criteria

I can swallow pills or have a working G-tube.

My cancer can be measured by scans and has grown despite previous treatments.

It's been over 4 weeks since my last cancer treatment and any side effects are mild or gone.

Exclusion Criteria

I have an immune system disorder or have been on steroids or other immune-weakening medicines recently.

I have not received a live vaccine within the last 30 days.

I have or had lung inflammation that needed steroids.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lenvatinib 20mg daily and pembrolizumab 200mg intravenously every 3 weeks

2 years

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Lenvatinib
• Pembrolizumab

Trial Overview The trial is testing the effectiveness and safety of lenvatinib combined with pembrolizumab in treating advanced salivary gland cancers. It aims to determine if these drugs can help control the cancer when it has recurred or spread elsewhere in the body.

Participant Groups

Group I: recurrent/metastatic non-ACC salivary gland cancers (R/M SGC). Experimental Treatment 2 Interventions

All eligible patients will undergo informed consent and screening for trial enrollment. Enrolled patients will receive a starting lenvatinib dose of 20mg daily taken orally and pembrolizumab 200mg intravenously every 3 weeks (1 cycle=3 weeks)

Group II: recurrent/metastatic adenoid cystic carcinoma (R/M ACC) Experimental Treatment 2 Interventions

All eligible patients will undergo informed consent and screening for trial enrollment. Enrolled patients will receive a starting lenvatinib dose of 20mg daily taken orally and pembrolizumab 200mg intravenously every 3 weeks (1 cycle=3 weeks)

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Eisai Inc.

Industry Sponsor

Trials

524

Recruited

161,000+

Founded

Eisai Inc. was established in 1995 as the U.S. subsidiary of Eisai Co., Ltd.

Headquarters

Woodcliff Lake, NJ, USA

Known For

Neurology and Oncology

Top Products

Aricept (donepezil), Lenvima (lenvatinib), Leqembi (lecanemab), Halaven (eribulin)

Lynn Kramer

Eisai Inc.

Chief Medical Officer since 2019

MD

Tatsuyuki Yasuno

Eisai Inc.

Chief Executive Officer since 2023

MBA from Kellogg School of Management, Northwestern University; Bachelor of Political Science from Waseda University

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

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]

The combination of lenvatinib, a multikinase inhibitor, and pembrolizumab, a PD-1 inhibitor, shows promising antitumor activity and durable responses in various solid tumors, as indicated by preliminary results from the LEAP clinical trial program.

This combination therapy has a manageable safety profile, suggesting it could be a valuable new treatment option for solid cancers that currently have limited therapeutic alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. Taylor, MH., Schmidt, EV., Dutcus, C., et al.[2021]

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]

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]

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 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]

A 65-year-old female patient with metastatic endometrial cancer developed grade 2 esophagitis likely related to lenvatinib treatment, which was characterized by dysphagia and mucosal lacerations in the esophagus.

The patient's symptoms improved significantly after stopping lenvatinib and starting a proton pump inhibitor (PPI), allowing for a successful resumption of lenvatinib at a reduced dose without recurrence of esophagitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Esophagitis as a complication of the combination of lenvatinib and pembrolizumab for advanced endometrial cancer: A case report. Fellouah, M., Auclair, MH., Fortin, S., et al.[2023]

In a phase 1b study involving 6 Japanese patients with metastatic solid tumors, the combination of lenvatinib and pembrolizumab was well-tolerated, with no dose-limiting toxicities reported.

The treatment showed promising antitumor activity, with an objective response rate of 33.3%, particularly in patients with urothelial cancer, indicating potential efficacy for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A feasibility study of lenvatinib plus pembrolizumab in Japanese patients with advanced solid tumors. Kitano, S., Fujiwara, Y., Shimizu, T., 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]

References

1. Switzerland 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. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Lenvatinib in Management of Solid Tumors. [2021]

3. England pubmed.ncbi.nlm.nih.gov

The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. [2021]

4. England 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. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Adverse events and oncologic outcomes with combination lenvatinib and pembrolizumab for the treatment of recurrent endometrial cancer. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma. [2023]

7. England 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. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Esophagitis as a complication of the combination of lenvatinib and pembrolizumab for advanced endometrial cancer: A case report. [2023]

9. Germany pubmed.ncbi.nlm.nih.gov

A feasibility study of lenvatinib plus pembrolizumab in Japanese patients with advanced solid tumors. [2022]

10. England 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. [2020]