Immune + Targeted Therapies for Renal Cell Carcinoma

Not currently recruiting at 63 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Immunosuppressants, Pembrolizumab, Lenvatinib, Belzutifan

Disqualifiers: Cardiovascular disease, Lung disease, Autoimmune, others

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

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new combinations of treatments for clear cell renal cell carcinoma (ccRCC), a type of kidney cancer. It focuses on individuals whose cancer has worsened after other treatments. Initially, the study will assess the safety of the treatments, followed by their effectiveness. Participants will receive different combinations of drugs, administered either by IV or as pills. Those whose kidney cancer has progressed after treatments involving specific immune or tumor growth blockers might be suitable for this trial. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants a chance to receive potentially groundbreaking therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy, you must stop it at least 7 days before starting the trial.

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

Research shows that the treatments tested in this trial have been safe in previous studies. Here's a simple overview:

1. **Pembrolizumab and Quavonlimab**: Studies found this combination has manageable side effects, meaning they can be handled well.

2. **Favezelimab and Pembrolizumab**: The safety of this combo matches earlier studies, suggesting no unexpected problems have occurred.

3. **Pembrolizumab and MK-4830**: Research indicates this combo is safe for use in solid tumors, with generally manageable side effects.

4. **Pembrolizumab and Belzutifan**: This combination is well-tolerated in advanced kidney cancer, meaning patients can handle it well.

5. **Belzutifan and Lenvatinib**: This pair has a safety record similar to past studies, with no new or unexpected side effects.

6. **Pembrolizumab and Lenvatinib**: This combination is already approved for advanced kidney cancer in several countries, showing effectiveness and consistent safety.

These treatments have been tested before, and studies suggest they are generally safe and well-tolerated. The safety lead-in phase of the study aims to confirm these safety profiles for new participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for renal cell carcinoma because they offer novel approaches compared to the standard options like sunitinib or pazopanib, which primarily target blood vessel growth. The coformulation of pembrolizumab and quavonlimab, as well as the combos with favezelimab and MK-4830, utilize immune checkpoint inhibitors, which help the immune system recognize and attack cancer cells more effectively. The pembrolizumab and belzutifan combination is noteworthy because belzutifan targets hypoxia-inducible factors, a different mechanism that can cut off the tumor’s energy supply. Meanwhile, treatments involving lenvatinib focus on blocking proteins that tumors need to grow and spread. These innovative mechanisms of action provide new avenues for treating renal cell carcinoma, potentially improving outcomes for patients.

What evidence suggests that this trial's treatments could be effective for renal cell carcinoma?

Research has shown that pembrolizumab, when combined with other treatments, can help treat advanced kidney cancer, known as renal cell carcinoma (RCC). In this trial, participants may receive different treatment combinations. One arm involves pembrolizumab combined with quavonlimab, which has shown promising results for people with advanced clear cell RCC. Another arm tests the combination of favezelimab and pembrolizumab, aiming to boost the body's immune response against cancer cells. Early studies indicate that pembrolizumab with MK-4830, another treatment arm, effectively targets tumors and is generally safe. Using pembrolizumab with belzutifan, also under study, has improved the time patients remain disease-free compared to pembrolizumab alone. Finally, the combinations of belzutifan and lenvatinib, or pembrolizumab and lenvatinib, are being tested for their ability to significantly slow disease progression. These combinations offer new hope for people with advanced RCC. ^{1 3 6 7 8}

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 renal cell carcinoma who've seen their cancer progress after treatment with specific systemic therapies. They must be able to take oral meds, have good organ function, controlled blood pressure, and no recent major surgery or active infections. Women of childbearing potential must use contraception and not be pregnant or breastfeeding.

Inclusion Criteria

I am not pregnant, breastfeeding, and if able to bear children, I am using contraception or abstaining from sex.

My kidney cancer worsened after treatment with specific immune or targeted therapies.

I can take pills by mouth.

Exclusion Criteria

I have an autoimmune disease but haven't needed systemic treatment in the last 2 years.

I have been treated with belzutifan before.

I have a preexisting abnormal connection between two parts inside my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

Demonstrate a tolerable safety profile for the combination of investigational agents

3 weeks

1 visit (in-person)

Efficacy

Evaluate the efficacy of experimental combinations of investigational agents

Up to 56 months

Regular visits (in-person) every 3-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Favezelimab
• MK-4830
• Pembrolizumab
• Quavonlimab

Trial Overview The study tests combinations of experimental drugs (MK-4830, Pembrolizumab/Quavonlimab, Favezelimab/Pembrolizumab) in two phases: first ensuring safety (no severe reactions), then checking if they work against kidney cancer that's worsened despite previous treatments.

How Is the Trial Designed?

Group I: Pembrolizumab + MK-4830 Experimental Treatment 2 Interventions

Participants will receive pembrolizumab 200 mg PLUS MK-4830 800 mg. Both pembrolizumab and MK-4830 will be administered IV Q3W for up to 35 administrations (up to \~2 years).

Group II: Pembrolizumab + Lenvatinib Experimental Treatment 2 Interventions

Participants will receive pembrolizumab 400 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered IV Q6W for up to 17 administrations (up to \~2 years). Lenvatinib will be administered orally QD until progressive disease or discontinuation.

Group III: Pembrolizumab + Belzutifan Experimental Treatment 2 Interventions

Participants will receive pembrolizumab 400 mg PLUS belzutifan 120 mg. Pembrolizumab will be administered IV Q6W for up to 17 administrations (up to \~ 2 years). Belzutifan will be administered orally once-daily (QD) until progressive disease or discontinuation.

Group IV: Coformulation Pembrolizumab/Quavonlimab Experimental Treatment 1 Intervention

Participants will receive pembrolizumab/quavonlimab (coformulation of pembrolizumab 400 mg and quavonlimab 25 mg). Pembrolizumab/quavonlimab will be administered intravenously (IV) once every 6 weeks (Q6W) for up to 17 administrations (up to \~2 years).

Group V: Coformulation Favezelimab/Pembrolizumab Experimental Treatment 1 Intervention

Participants will receive favezelimab/pembrolizumab (coformulation of favezelimab 800 mg and pembrolizumab 200 mg). Favezelimab/Pembrolizumab will be administered IV once every 3 weeks (Q3W) for up to 35 administrations (up to \~2 years).

Group VI: Belzutifan + Lenvatinib Experimental Treatment 2 Interventions

Participants will receive Belzutifan 120 mg PLUS lenvatinib 20 mg. Both belzutifan and lenvatinib will be administered orally QD until progressive disease or discontinuation.

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 subgroup analysis of 94 Japanese patients with metastatic renal cell carcinoma, the combination of pembrolizumab and axitinib showed improved overall survival and progression-free survival compared to sunitinib, consistent with results from the larger global study.

The safety profile was also favorable, with fewer grade ≥3 treatment-related adverse events in the pembrolizumab-axitinib group (70%) compared to sunitinib (78%), and no deaths from treatment-related adverse events were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus axitinib versus sunitinib in metastatic renal cell carcinoma: outcomes of Japanese patients enrolled in the randomized, phase III, open-label KEYNOTE-426 study. Tamada, S., Kondoh, C., Matsubara, N., et al.[2022]

Targeted therapies and immunotherapies, including checkpoint inhibitors like anti-CTLA-4 and anti-PD-1, are showing promise in treating kidney cancer, particularly in metastatic clear cell renal carcinoma.

Recent clinical trials, such as CheckMate-025 and AGS-003, are exploring the effectiveness of these therapies, indicating a shift towards combination treatments that may enhance patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy of renal cell cancer]. Géczi, L., Nagyiványi, K., Maráz, A.[2019]

In a phase II study involving 110 patients with advanced clear cell renal cell carcinoma (ccRCC), pembrolizumab demonstrated a 36.4% objective response rate, indicating significant antitumor activity as a first-line treatment.

The treatment was generally well-tolerated, with 30% of patients experiencing grade 3-5 adverse events, primarily colitis and diarrhea, which aligns with safety profiles observed in other cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-Label, Single-Arm Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Clear Cell Renal Cell Carcinoma. McDermott, DF., Lee, JL., Bjarnason, GA., et al.[2022]

In the KEYNOTE-B61 trial involving 158 patients with advanced non-clear-cell renal cell carcinoma, the combination of pembrolizumab and lenvatinib demonstrated a 49% objective response rate, indicating significant antitumor activity as a first-line treatment.

The safety profile was consistent with previous studies, with 51% of patients experiencing grade 3-4 treatment-related adverse events, primarily hypertension, but no deaths were attributed to the treatment itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus lenvatinib as first-line therapy for advanced non-clear-cell renal cell carcinoma (KEYNOTE-B61): a single-arm, multicentre, phase 2 trial. Albiges, L., Gurney, H., Atduev, V., 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]

Adjuvant pembrolizumab significantly improves disease-free survival in patients with high-risk renal cell carcinoma (RCC) after surgery, as shown in the KEYNOTE 564 trial.

Pembrolizumab is an effective and well-tolerated treatment option for patients with surgically resected RCC, paving the way for future research on patient selection and biomarkers for therapy response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant therapy for patients with renal cell carcinoma following surgery: a focus on pembrolizumab. Serzan, M., Atkins, MB.[2022]

The combination of axitinib and pembrolizumab shows a high response rate of 73% in patients with previously untreated advanced renal cell carcinoma, indicating strong efficacy for this treatment regimen.

This finding suggests that the dual approach of targeting both tumor growth and immune response may be effective in managing advanced kidney cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib plus Pembrolizumab Is Effective in Renal Cell Carcinoma. [2019]

In the phase 3 KEYNOTE-426 trial involving 861 patients, the combination of pembrolizumab and axitinib significantly improved overall survival and progression-free survival compared to sunitinib for advanced renal cell carcinoma.

While both treatment groups showed similar health-related quality of life outcomes, the time to confirmed deterioration favored sunitinib, indicating that while pembrolizumab + axitinib is more effective in extending survival, it does not significantly enhance quality of life compared to sunitinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related Quality of Life Analysis from KEYNOTE-426: Pembrolizumab plus Axitinib Versus Sunitinib for Advanced Renal Cell Carcinoma. Bedke, J., Rini, BI., Plimack, ER., et al.[2022]

Citations

1. targetedonc.com targetedonc.com/view/interim-efficacy-data-favor-belzutifan-lenvatinib-in-advanced-rcc

Interim Efficacy Data Favor Belzutifan/Lenvatinib in ... The combination of belzutifan and lenvatinib showed significant PFS improvement in advanced RCC patients compared to cabozantinib. Although OS ...

2. onclive.com onclive.com/view/belzutifan-based-combinations-meet-dfs-pfs-end-points-in-renal-cell-carcinoma

Belzutifan-Based Combinations Meet DFS, PFS End ... LITESPARK-011 and LITESPARK-022 trials showed significant PFS and DFS improvements in RCC with belzutifan combinations, surpassing cabozantinib ...

3. merck.com merck.com/news/merck-and-eisai-announce-welireg-belzutifan-plus-lenvima-lenvatinib-met-primary-endpoint-of-progression-free-survival-pfs-in-certain-previously-treated-patients-with-advanced-renal-c/

Merck and Eisai Announce WELIREG® (belzutifan) Plus ... At a pre-specified interim analysis, WELIREG plus LENVIMA demonstrated a statistically significant and clinically meaningful improvement in PFS compared to ...

4. cancernetwork.com cancernetwork.com/view/belzutifan-plus-lenvatinib-improves-pfs-orr-in-advanced-pretreated-rcc

Belzutifan Plus Lenvatinib Improves PFS/ORR in ... Belzutifan/lenvatinib also showed a favorable trend toward improvement for overall survival in this advanced renal cell carcinoma population.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04586231

NCT04586231 | A Study of Belzutifan (MK-6482) in ... This study will compare the efficacy and safety of belzutifan + lenvatinib versus cabozantinib in participants with advanced renal cell carcinoma (RCC)

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.4553

Belzutifan plus lenvatinib for patients (pts) with advanced ... Preliminary data from the belzutifan + lenvatinib combination exhibited promising antitumor activity in pts with ccRCC that progressed on PD-1/L1 inhibitors ...

7. eisai.com eisai.com/news/2025/news202575.html

Merck & Co., Inc., Rahway, NJ, USA and ... KEYTRUDA plus LENVIMA is approved in the U.S., the EU, Japan and other countries for the treatment of advanced RCC and certain types of advanced ...

8. cancernetwork.com cancernetwork.com/view/lenvatinib-belzutifan-exhibits-durable-antitumor-activity-safety-in-ccrcc

Lenvatinib/Belzutifan Exhibits Durable Antitumor Activity ... Treatment with lenvatinib (Lenvima) in combination with belzutifan (Welireg) exhibited durable antitumor activity and a safety profile consistent with prior ...