Pembrolizumab/Quavonlimab + Lenvatinib for Liver Cancer

No longer recruiting at 53 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme Corp.

Must be taking: Antivirals, Antihypertensives

Must not be taking: Anticoagulants, Immunosuppressants

Disqualifiers: Variceal bleeding, Cardiovascular impairment, 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: 6

Duration: Up to 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess the safety and effectiveness of combining two drugs, pembrolizumab/quavonlimab (an immunotherapy) and lenvatinib (a targeted therapy), for treating liver cancer. It targets individuals with liver cancer that cannot be treated with surgery or other local treatments. The trial seeks participants who have not experienced major bleeding issues recently and have managed their blood pressure. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

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

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants must have adequately controlled blood pressure, which can be managed with or without medications. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Earlier studies have shown that the combination of pembrolizumab and lenvatinib is safe for treating liver cancer. Over 80% of liver cancer patients found this treatment both safe and effective. This combination has also been successful in treating other cancers, such as kidney cancer.

Although some side effects have been reported, most people tolerate these treatments well. As this study is in an early phase, researchers continue to closely monitor safety, but evidence already suggests it is safe for humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of pembrolizumab/quavonlimab and lenvatinib for liver cancer because it offers a new approach to treatment. Unlike standard therapies that often target specific tumor cells, pembrolizumab/quavonlimab works by unleashing the immune system to recognize and attack cancer cells more effectively. This combination also includes lenvatinib, a targeted therapy that inhibits tumor growth by blocking the formation of new blood vessels. Together, these treatments aim to provide a more comprehensive attack on liver cancer, potentially improving outcomes for patients who may not respond well to existing options.

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

Studies have shown that using pembrolizumab and quavonlimab together with lenvatinib is generally safe for treating liver cancer. Research indicates that this combination, which participants in this trial will receive, has shown promising results in early trials. Pembrolizumab helps the immune system fight cancer, while quavonlimab and lenvatinib work to stop cancer growth. Previous patients experienced positive outcomes with this combination. These findings suggest it could be an effective option for people with hepatocellular carcinoma, a common type of liver cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for adults with advanced liver cancer (Hepatocellular Carcinoma) who haven't had certain treatments. They should have a specific stage of the disease, good liver function, controlled blood pressure, and no major health issues like brain metastases or recent surgeries. People with HIV, active infections besides hepatitis B/C, severe allergies to study drugs, or other cancers aren't eligible.

Inclusion Criteria

My organs are functioning well.

You are expected to live for more than 3 months.

My blood pressure is under control, with or without medication.

Exclusion Criteria

I have a condition that affects how my body absorbs medication.

You have recently taken part in a study testing a new medication or device within the past month.

I have a serious wound or fracture that is not healing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab/quavonlimab via IV infusion every 6 weeks for up to 2 years, plus lenvatinib orally until progressive disease or unacceptable toxicity for up to 5 years

Up to 5 years

IV infusion every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 28 months

What Are the Treatments Tested in This Trial?

Interventions

• Lenvatinib
• Pembrolizumab/Quavonlimab

Trial Overview The trial tests a combination of two drugs: Pembrolizumab/Quavonlimab and Lenvatinib in patients with first-line Hepatocellular Carcinoma. It aims to see how safe this combo is and how well it works against this type of liver cancer without comparing it to another treatment.

How Is the Trial Designed?

Group I: Pembrolizumab/Quavonlimab + Lenvatinib Experimental Treatment 3 Interventions

Participants receive pembrolizumab/quavonlimab via intravenous (IV) infusion every 6 weeks (Q6W) for up to 2 years, plus lenvatinib orally (based on actual body weight at screening) until progressive disease or unacceptable toxicity for up to 5 years. In the event of discontinuation of pembrolizumab/quavonlimab due to intolerable toxicity, re-initiation of treatment with pembrolizumab may be considered.

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?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

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

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

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

Merck Sharp & Dohme LLC

Lead 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

Published Research Related to This Trial

In a phase 3 study involving 794 patients with unresectable hepatocellular carcinoma, the combination of pembrolizumab and lenvatinib showed a median overall survival of 21.2 months, compared to 19.0 months for lenvatinib plus placebo, indicating a potential benefit in survival.

Despite the observed improvement in overall survival, the combination therapy did not meet the predefined significance thresholds for overall survival and progression-free survival, suggesting that it may not warrant a change in current treatment practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib plus pembrolizumab versus lenvatinib plus placebo for advanced hepatocellular carcinoma (LEAP-002): a randomised, double-blind, phase 3 trial. Llovet, JM., Kudo, M., Merle, P., 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]

In a phase Ib study involving 104 patients with unresectable hepatocellular carcinoma (uHCC), the combination of lenvatinib and pembrolizumab demonstrated significant antitumor activity, with an objective response rate of 46% according to modified RECIST criteria.

The treatment was well-tolerated, with manageable toxicities and no new safety signals identified, indicating that this combination could be a viable option for patients with uHCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma. Finn, RS., Ikeda, M., Zhu, AX., et al.[2022]

In a study of 71 patients with unresectable hepatocellular carcinoma (uHCC), the combination of lenvatinib and pembrolizumab demonstrated a high disease control rate of 84.1% for first-line treatment, indicating its efficacy in managing this condition.

The treatment did not adversely affect liver function, as measured by the Albumin-Bilirubin (ALBI) score, and factors such as prior nivolumab failure and Child-Pugh class B were associated with poorer progression-free and overall survival, highlighting the need for further investigation in these subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib plus pembrolizumab for systemic therapy-naïve and -experienced unresectable hepatocellular carcinoma. Wu, CJ., Lee, PC., Hung, YW., et al.[2022]

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 significantly improved treatment outcomes for patients with advanced endometrial cancer compared to chemotherapy, regardless of tumor characteristics, based on data from Study-309/KEYNOTE-775.

Common adverse reactions included hypothyroidism, hypertension, and fatigue, with effective management strategies involving patient education, monitoring, and appropriate dose adjustments to minimize treatment interruptions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization and Management of Adverse Reactions in Patients With Advanced Endometrial Cancer Receiving Lenvatinib Plus Pembrolizumab. Colombo, N., Lorusso, D., Monk, BJ., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.484

Phase 2 KEYSTEP-004 study. | Journal of Clinical Oncology The coformulation of quavonlimab and pembrolizumab in combination with lenvatinib demonstrated manageable safety; further investigation is warranted.

2. eisaimedicalinformation.com eisaimedicalinformation.com/-/media/Files/EisaiMedicalInformation/Oncology/Congress-Materials/ASCO-GI-2024/Rimassa_ASCO-GI-2024_KEYSTEP-004-FA.pdf?hash=d452371a-4520-4ee3-a736-47860a49946f

Coformulated Quavonlimab and Pembrolizumab in ... Hepatocellular Carcinoma ... combination with lenvatinib demonstrated manageable safety. • The triplet provided encouraging results. References.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04740307

Study Details | NCT04740307 | Safety and Efficacy of ... The purpose of this study is to evaluate the safety and efficacy of fixed dose coformulated pembrolizumab/quavonlimab (MK-1308A) plus lenvatinib in a first ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(21)01379-X/fulltext

P-135 Pembrolizumab/quavonlimab coformulation in ... An open-label phase 2 study investigating the safety and efficacy of MK-1308A, a coformulation of pembrolizumab (PD-1 inhibitor) and quavonlimab (CTLA-4 ...

5. onclive.com onclive.com/view/pembrolizumab-lenvatinib-plus-belzutifan-or-quavonlimab-under-investigation-in-advanced-clear-cell-rcc

Pembrolizumab/Lenvatinib Plus Belzutifan or ... - OncLive A phase 3 clinical trial will compare the safety and efficacy of a co-formulation of pembrolizumab and quavonlimab plus lenvatinib.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10540481/

Combined use of pembrolizumab and lenvatinib: A review Data suggests that combination therapy with pembrolizumab and lenvatinib can be used first line for clear cell renal carcinoma in patients with favorable risk.

7. merck.com merck.com/news/keytruda-pembrolizumab-plus-lenvima-lenvatinib-in-combination-with-transarterial-chemoembolization-significantly-improved-progression-free-survival-compared-to-tace-alone-in-patients-w/

KEYTRUDA® (pembrolizumab) Plus LENVIMA® ... KEYTRUDA plus LENVIMA in combination with TACE reduced the risk of disease progression or death by 34% compared to TACE alone.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04425226

Study Details | NCT04425226 | Pembrolizumab and ... Objectives of Study：This study will evaluate the safety and efficacy of pembrolizumab in combination with lenvatinib as neoadjuvant therapy in participants ...

9. conquer-magazine.com conquer-magazine.com/issues/special-issues/august-2020-asco-highlights/lenvima-and-keytruda-combination-shows-promise-in-patients-with-inoperable-liver-cancer

Lenvima and Keytruda Combination Shows Promise in ... Treatment with lenvatinib plus pembrolizumab is safe and effective for patients with unresectable liver cancer; More than 80% of patients with liver cancer ...

10. onclive.com onclive.com/view/pembrolizumab-lenvatinib-combo-misses-survival-end-points-in-unresectable-hcc

Pembrolizumab/Lenvatinib Combo Misses Survival End ... The addition of pembrolizumab to lenvatinib did not significantly improve overall survival or progression-free survival over lenvatinib alone.