Pembrolizumab + Cabozantinib for Kidney Cancer

No longer recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Colorado, Denver

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, Active TB, CNS metastases, 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: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, pembrolizumab (an immunotherapy drug) and cabozantinib (a targeted therapy), to determine if they work better together in treating advanced kidney cancer that has recurred or spread. The goal is to find the optimal dose of cabozantinib to use with pembrolizumab and then assess the effectiveness of this combination in treating the cancer. The study seeks participants diagnosed with renal cell carcinoma, specifically those with advanced or metastatic cancer. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Do I have to stop taking my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain immunosuppressive therapies or have had recent treatments with other investigational drugs or cancer therapies. 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?

Research has shown that the combination of pembrolizumab and cabozantinib has been tested for safety in patients with advanced kidney cancer. Studies have found that this combination is generally well-tolerated. Common side effects include tiredness, diarrhea, and high blood pressure, which are usually manageable with proper care.

Both pembrolizumab and cabozantinib have been used separately to treat other conditions, and their safety is well-documented. Pembrolizumab is an immune therapy that helps the body fight cancer cells, while cabozantinib is a drug that stops cancer from growing.

In these studies, serious side effects were less common, but they can occur. Some patients reported liver problems and changes in blood tests, which doctors monitor closely. Overall, the available evidence suggests that this treatment combination is safe enough for further testing in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of pembrolizumab and cabozantinib for kidney cancer because it offers a novel approach compared to standard treatments. Unlike typical therapies that focus on singular mechanisms, this duo combines an immune checkpoint inhibitor, pembrolizumab, which unleashes the immune system to attack cancer cells, with cabozantinib, a tyrosine kinase inhibitor that blocks signals tumors use to grow and spread. This dual action not only targets the cancer directly but also enhances the body's own defenses, potentially leading to more effective and durable responses.

What evidence suggests that this trial's treatments could be effective for kidney cancer?

This trial will evaluate the combination of pembrolizumab and cabozantinib for treating advanced kidney cancer, known as metastatic renal cell carcinoma (mRCC). Participants will receive varying dosages of cabozantinib alongside pembrolizumab to determine the most effective regimen. Studies have shown that using pembrolizumab and cabozantinib together can help patients live longer and respond better to treatment compared to some other options. Pembrolizumab aids the immune system in attacking cancer cells, while cabozantinib blocks certain pathways that promote tumor growth. Early findings suggest that this drug combination could be a promising approach for treating kidney cancer. ^{1 3 4 6 7}

Who Is on the Research Team?

Elaine T. Lam, MD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

Adults with advanced kidney cancer who can provide a tumor sample and have good performance status. They must not be pregnant, agree to use contraception, and have no recent treatments or significant health issues that could interfere with the trial. Prior immune therapy is allowed if there were no severe side effects.

Inclusion Criteria

My kidney cancer diagnosis was confirmed through lab tests.

My cancer has spread or come back and is advanced.

Be willing and able to provide written informed consent/assent for the trial

Exclusion Criteria

I have not been in a clinical trial for a new treatment or device within the last 4 weeks.

You have a current, active Hepatitis B or Hepatitis C infection.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Sequential dose escalation of cabozantinib with standard dose pembrolizumab to determine the recommended phase 2 dose (RP2D).

21 days per cycle, until disease progression or unacceptable toxicity

1 visit per cycle (in-person)

Phase II Treatment

Participants receive cabozantinib at the RP2D in combination with pembrolizumab for up to 35 cycles.

21 days per cycle, up to 35 cycles

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 5 years

Open-label extension (optional)

Participants who stop pembrolizumab after 35 cycles with stable disease or better may be eligible for up to an additional 17 cycles of pembrolizumab treatment.

Approximately 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Cabozantinib
• Pembrolizumab

Trial Overview

The study tests Pembrolizumab combined with Cabozantinib in patients with metastatic renal cell carcinoma. Phase I finds the safest dose of Cabozantinib alongside standard Pembrolizumab, then Phase II expands this combination treatment to more patients.

How Is the Trial Designed?

Group I: Phase 2: Pembrolizumab 200 mg plus Cabozantinib at the RP2D Experimental Treatment 2 Interventions

Pembrolizumab 200 mg intravenous (IV) infusion on day 1 of each 21-day cycle in combination with cabozantinib at the RP2D orally once daily for up to 35 cycles, until disease progression, unacceptable toxicity, or consent withdrawal. All participants who stop pembrolizumab after 35 cycles with SD or better may be eligible for up to an additional 17 cycles (approximately 1 year) of pembrolizumab treatment if they progress after stopping pembrolizumab from the initial treatment phase.

Group II: Phase 1: Pembrolizumab 200 mg plus Cabozantinib 60mg Experimental Treatment 2 Interventions

Pembrolizumab 200 mg intravenous (IV) infusion on day 1 of each 21-day cycle in combination with cabozantinib 60 mg orally once daily until disease progression, unacceptable toxicity, or consent withdrawal.

Group III: Phase 1: Pembrolizumab 200 mg plus Cabozantinib 40mg Experimental Treatment 2 Interventions

Pembrolizumab 200 mg intravenous (IV) infusion on day 1 of each 21-day cycle in combination with cabozantinib 40 mg orally once daily until disease progression, unacceptable toxicity, or consent withdrawal.

Cabozantinib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in United States as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Canada as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Japan as Cabometyx for:

• Renal cell carcinoma

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

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

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/37377613/

A Phase I/II Clinical Trial of Pembrolizumab and Cabozantinib ...

This study evaluated the safety and effectiveness of the combination of pembrolizumab and cabozantinib in patients with mRCC.

2.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.4544

Phase I/II trial of pembrolizumab and cabozantinib in the ...

Cabozantinib real-world effectiveness in the first through fourth-line settings for the treatment of metastatic renal cell carcinoma (mRCC): ...

3.

aacrjournals.org

aacrjournals.org/cancerrescommun/article/3/6/1004/727208/A-Phase-I-II-Clinical-Trial-of-Pembrolizumab-and

A Phase I/II Clinical Trial of Pembrolizumab and Cabozantinib ...

This phase I/II clinical trial evaluated the safety and efficacy of pembrolizumab and cabozantinib in patients with mRCC.

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9974999/

Real-world Treatment Patterns and Clinical Outcomes for ...

Comparative effectiveness of front-line ipilimumab and nivolumab or axitinib and pembrolizumab in metastatic clear cell renal cell carcinoma. Oncologist. In ...

5.

actionkidneycancer.org

actionkidneycancer.org/comparison-of-real-world-outcomes-from-combination-therapies-for-advanced-kidney-cancer/

Comparison of real-world outcomes from combination ...

In conclusion, lenvatinib plus pembrolizumab, or nivolumab plus cabozantinib had better survival outcomes and response to treatment compared to ...

6.

keytrudalenvimahcp.com

keytrudalenvimahcp.com/advanced-renal-cell-carcinoma/

Advanced Renal Cell Carcinoma: Efficacy and Safety Results

Health care professionals can review efficacy data and safety results for a first-line treatment of adult patients with advanced renal cell carcinoma (RCC).

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S030573722100181X

Management of adverse events associated with ...

Cabozantinib + nivolumab is a first-line therapy for patients with advanced RCC. Proper AE management improves safety, prolongs treatment, and may optimize ...