What side effects are associated with this type of intervention?

Common side effects of Pembrolizumab, a PD-1 inhibitor, include fatigue, rash, pruritus, diarrhea, and immune-related adverse events such as pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Cabozantinib, a tyrosine kinase inhibitor, often causes hypertension, diarrhea, fatigue, decreased appetite, hand-foot syndrome, and elevated liver enzymes. Both drugs can lead to significant toxicities that require careful monitoring and management.

What prior FDA approvals exist?

Pembrolizumab, a PD-1 inhibitor, has been approved by the FDA for use in renal cell carcinoma, often in combination with other agents such as axitinib, another tyrosine kinase inhibitor. Cabozantinib, a tyrosine kinase inhibitor, has also received FDA approval for the treatment of advanced renal cell carcinoma. These approvals are based on clinical trials demonstrating their efficacy in improving outcomes for patients with advanced kidney cancer.

What other types of research exist?

Promising novel alternatives for kidney cancer treatment in 2024 include: <ol> <li>Nivolumab plus Ipilimumab (Checkpoint Inhibitors) - demonstrated efficacy in the CheckMate 214 trial.</li> <li></li> </ol> Atezolizumab plus Bevacizumab (Checkpoint Inhibitor and VEGF Inhibitor) - shown to be effective in the IMmotion151 trial. 3. Lenvatinib plus Pembrolizumab (Tyrosine Kinase Inhibitor and PD-1 Inhibitor) - positive results in the CLEAR study. 4. Avelumab plus Axitinib (Checkpoint Inhibitor and Tyrosine Kinase Inhibitor) - promising outcomes in the JAVELIN Renal 101 trial.

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Tyrosine Kinase Inhibitor

Pembrolizumab + Cabozantinib for Kidney Cancer

Phase 1 & 2

Waitlist Available

Led By Elaine Lam, MD

Research Sponsored by University of Colorado, Denver

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Subjects must have histological or cytological documentation of renal cell carcinoma

Subjects must have locally advanced, recurrent, or metastatic disease

Must not have

Has received a live vaccine within 30 days of planned start of study therapy

Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy equivalent to ≥ 10 mg/day of prednisone, or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up time of first response as measured by recist 1.1 to time of progression or death, whichever comes first, up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of two drugs, pembrolizumab and cabozantinib, in patients with advanced kidney cancer. Pembrolizumab boosts the immune system to fight cancer, and cabozantinib stops cancer cells from growing. The goal is to find the best dose and see how well the combination works. Cabozantinib was approved for the treatment of advanced kidney cancer after other treatments.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include fatigue, diarrhea, liver toxicity, high blood pressure, mouth sores, hand-foot syndrome (redness and pain on palms or soles), immune-related reactions like thyroid dysfunction or lung inflammation.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My kidney cancer diagnosis was confirmed through lab tests.

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My cancer has spread or come back and is advanced.

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I have available tumor samples in paraffin blocks or at least 10 slides.

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I am fully active or restricted in physically strenuous activity but can do light work.

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My organ functions are within the required range.

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My cancer has not spread to my bones.

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I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I have an immune system disorder or have been on strong immune system drugs recently.

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I have been treated with pembrolizumab before.

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I haven't had cancer treatment in the last 2 weeks or still have side effects.

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I have an autoimmune disease treated with medication in the last 2 years.

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I have had an organ transplant.

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I have had osteonecrosis of the jaw.

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I have had reversible posterior leukoencephalopathy syndrome.

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I have cancer that has spread to my brain or spinal cord.

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I cannot swallow pills.

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I have been diagnosed with HIV.

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I am currently on IV antibiotics for an infection.

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I have another cancer that is getting worse or needs treatment.

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I haven't had cancer treatment with monoclonal antibodies in the last 4 weeks.

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I have been treated with cabozantinib before.

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I have an active tuberculosis infection.

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I have had pneumonitis treated with steroids or currently have it.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ time of first response as measured by recist 1.1 to time of progression or death, whichever comes first, up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~time of first response as measured by recist 1.1 to time of progression or death, whichever comes first, up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and time of first response as measured by recist 1.1 to time of progression or death, whichever comes first, up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Efficacy of Pembrolizumab and Cabozantinib Based on Objective Response Rate

Secondary study objectives

Disease Control Rate (DCR), AKA Clinical Benefit Rate (CBR)

Dose Limiting Toxicities

Duration of Response

+3 more

Side effects data

From 2024 Phase 3 trial • 804 Patients • NCT03040999

64%

Radiation skin injury

63%

Stomatitis

58%

Anaemia

56%

Nausea

48%

Dry mouth

45%

Constipation

45%

Weight decreased

44%

Dysphagia

42%

Neutrophil count decreased

33%

Dysgeusia

33%

Vomiting

32%

Fatigue

31%

White blood cell count decreased

28%

Hypomagnesaemia

26%

Decreased appetite

25%

Hypothyroidism

25%

Hypokalaemia

24%

Lymphocyte count decreased

24%

Platelet count decreased

23%

Oropharyngeal pain

23%

Blood creatinine increased

22%

Diarrhoea

22%

Odynophagia

20%

Hypoacusis

20%

Alanine aminotransferase increased

20%

Hyponatraemia

19%

Tinnitus

19%

Oral candidiasis

19%

Asthenia

16%

Pyrexia

16%

Cough

15%

Aspartate aminotransferase increased

15%

Rash

14%

Insomnia

13%

Acute kidney injury

13%

Pharyngeal inflammation

13%

Pruritus

12%

Dysphonia

12%

Gamma-glutamyltransferase increased

11%

Pneumonia

11%

Dehydration

10%

Hyperthyroidism

10%

Hypoalbuminaemia

10%

Hypocalcaemia

10%

Headache

10%

Productive cough

Neck pain

Peripheral sensory neuropathy

Gastrooesophageal reflux disease

Hiccups

Hyperglycaemia

Hyperuricaemia

Dizziness

Hypophosphataemia

Urinary tract infection

Ear pain

Localised oedema

Hyperkalaemia

Erythema

Oral pain

Abdominal pain upper

Arthralgia

Anxiety

Febrile neutropenia

Dyspepsia

Saliva altered

Back pain

Oedema peripheral

Hypertension

Dyspnoea

Nasopharyngitis

Alopecia

Dry skin

Sepsis

Pneumonia aspiration

Trismus

Pneumonitis

Laryngeal oedema

Malnutrition

Pharyngeal haemorrhage

Cellulitis

Septic shock

Systemic infection

Clostridium difficile colitis

Cardiac arrest

Death

Bronchitis

Hepatitis

Immune-mediated hepatitis

Oesophagitis

General physical health deterioration

Hypophagia

Tumour haemorrhage

Cerebrovascular accident

Syncope

Acute respiratory failure

Aspiration

Colitis

Mouth haemorrhage

Hypersensitivity

Acute myocardial infarction

Abscess neck

Device related infection

Stoma site infection

Vascular device infection

Wound infection

Hypercalcaemia

Pulmonary embolism

Respiratory failure

100%

80%

60%

40%

20%

Study treatment Arm

Pembrolizumab + CRT Followed by Pembrolizumab

Placebo + CRT Followed by Placebo

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: Phase 2: Pembrolizumab 200 mg plus Cabozantinib at the RP2DExperimental Treatment2 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 60mgExperimental Treatment2 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 40mgExperimental Treatment2 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cabozantinib

2020

Completed Phase 2

~2360

Pembrolizumab

2017

Completed Phase 3

~3150

0 / 24Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Pembrolizumab, a PD-1 inhibitor, enhances the immune system's ability to recognize and attack cancer cells by blocking the PD-1 pathway, which tumors use to evade immune detection. Cabozantinib, a tyrosine kinase inhibitor, targets multiple kinases involved in tumor growth and angiogenesis, disrupting the signaling pathways that promote cancer cell proliferation and blood vessel formation. These mechanisms are vital for kidney cancer patients as they offer insights into how these treatments can control tumor growth and improve survival outcomes.