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Checkpoint Inhibitor

Immunotherapy + Cabozantinib for Advanced Kidney Cancer

Phase 3

Waitlist Available

Led By Tian Zhang

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

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

Must have

Must be intermediate or poor risk patient per International Metastatic Renal Cell Carcinoma Database (IMDC) criteria

Any metastatic disease, including visceral, lymph node, other soft tissue and bone, measurable per RECIST 1.1.

Must not have

Active autoimmune disease requiring ongoing therapy

Active treatment with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct Xa inhibitor betrixaban or platelet inhibitors (e.g., clopidogrel) within 5 days of registration

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial is testing a new combination treatment for patients with untreated renal cell carcinoma. The usual treatment is immunotherapy with ipilimumab and nivolumab, followed by nivolumab alone. The new treatment adds cabozantinib to nivolumab after initial treatment with ipilimumab and nivolumab. It is not yet known if this new combination treatment is better than the usual treatment.

Who is the study for?

This trial is for adults with advanced kidney cancer that hasn't been treated yet. Participants should have a certain level of physical fitness (Karnofsky performance status >= 70%), measurable disease, and be at an intermediate or poor risk according to specific criteria. They can't join if they've had certain treatments before, have active autoimmune diseases, uncontrolled conditions like hypertension or infections like HIV with detectable viral load, or are pregnant.

What is being tested?

The study compares standard immunotherapy treatment using Nivolumab and Ipilimumab followed by Nivolumab alone versus the same regimen followed by a combination of Nivolumab with Cabozantinib. The goal is to see if adding Cabozantinib improves outcomes in untreated renal cell carcinoma that has spread.

What are the potential side effects?

Possible side effects include immune-related reactions affecting organs, high blood pressure from Cabozantinib, fatigue, liver enzyme changes, digestive issues such as diarrhea from Ipilimumab and skin problems. Each patient may experience side effects differently.

Eligibility Criteria

Inclusion Criteria

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

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My kidney cancer is classified as intermediate or poor risk.

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My cancer has spread and can be measured by scans.

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I am at intermediate or poor risk for kidney cancer according to specific health criteria.

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My cancer has spread and can be measured by scans.

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I have not been treated with PD-1, PD-L1, or CTLA-4 inhibitors.

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I am 18 years old or older.

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I am able to care for myself but may not be able to do active work.

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My kidney cancer diagnosis includes clear cell characteristics.

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It has been less than 80 days since my last ipilimumab/nivolumab dose.

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I have not had any systemic therapy for kidney cancer.

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I am able to care for myself but may not be able to do active work.

Exclusion Criteria

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

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I am currently being treated for an autoimmune disease.

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I haven't taken blood thinners or platelet inhibitors in the last 5 days.

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I have not had major surgery in the last 4 weeks.

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My adrenal glands are not working properly and it's not under control.

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I have lung lesions with cavities or disease in my airways.

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My cancer is growing into or around major blood vessels.

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I am not taking immunosuppressive drugs or more than 10 mg of prednisone daily.

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I haven't had a major heart attack or severe heart failure symptoms in the last 6 months.

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I have not had a blood clot in an artery in the last 6 months.

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I have had pancreatitis, an organ transplant, or congenital QT syndrome.

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My thyroid condition has not been treated.

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I am experiencing significant side effects from past treatments.

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My liver function is moderately to severely impaired.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 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

Overall survival (OS)

Secondary study objectives

Complete response (CR) (randomized patients)

Incidence of adverse events

Objective response

+2 more

Other study objectives

Estimates of OS by ethnicity

Estimates of OS by race

Estimates of OS by sex

Side effects data

From 2022 Phase 2 trial • 45 Patients • NCT02101736

95%

HYPOTHYROIDISM

73%

DIARRHEA

55%

WEIGHT LOSS

50%

FATIGUE

41%

ALANINE AMINOTRANSFERASE INCREASED

41%

Neutrophil Count Decreased

41%

ASPARTATE AMINOTRANSFERASE INCREASED

41%

VOMITING

41%

ANOREXIA

41%

NAUSEA

36%

HYPERTENSION

36%

HEADACHE

36%

PALMAR-PLANTAR ERYTHRODYSESTHESIA SYNDROME

36%

PAIN IN EXTREMITY

32%

PROTEINURIA

32%

PAIN

27%

White Blood Cell Count Decreased

27%

ABDOMINAL PAIN

23%

PLATELET COUNT DECREASE

23%

HYPONATREMIA

23%

Decreased Platelet Count

23%

Platelet Count Decreased

23%

Renal & Urinary Disorders - Other, Ketonuria

23%

Skin Hypopigmentation

23%

HAIR COLOR CHANGE

18%

Upper Respiratory Infection

18%

HEMOGLOBIN INCREASED

18%

HYPOKALEMIA

18%

HYPOPHOSPHATEMIA

18%

Alopecia

18%

Hyperkalemia

14%

HYPERGLYCEMIA

14%

Pruritis

14%

HYPOGLYCEMIA

14%

Rash Acneiform

14%

Rash Maculopapular

14%

BILIRUBIN INCREASED

14%

ACNEIFORM RASH

14%

Cough

14%

Blood Bilirubin Increased

14%

DIZZINESS

14%

Skin And Subcutaneous Disorders - Other, Achromotricia

14%

CONSTIPATION

14%

Fever

NASAL CONGESTION

TUMOR PAIN

Papulopustular Rash

ALKALINE PHOSPHATASE INCREASED

Creatinine Increased

Back Pain

ABSOLUTE NEUTROPHIL COUNT DECREASED

LIPASE INCREASED

Skin And Subcutaneous Tissue Disorders- Other, Rash Unspecified

Paresthesia

ORAL PAIN

LYMPHOCYTE COUNT DECREASED

WEIGHT GAIN

HYPOCALCEMIA

DRY SKIN

Hypotension

Injury, Poisoning And Procedural Complications - Other, Ankle Injury

Peripheral Sensory Neuropathy

Joint Range Of Motion Decreased

Hypertension

SERUM AMYLASE INCREASED

Investigations - Other, Eosinophilia

Allergic Rhinitis

ANXIETY

Hypermagnesemia

Rash Ezcematoid

Behaviour Disturbance

Scalp Pain

Psychiatric Disorders - Other, Mood Swings

Sinus Tachycardia

Periodontal Disease

Myalgia

Tooth Infection

URINARY FREQUENCY

Conjunctivitis

Sinusitis

Syncope

Activated Partial Thromboplastin Time Prolonged

Breast Pain

Peripheral Motor Neuropathy

Scalp Lesion

Sore Throat

Tachycardia

JOINT RANGE OF MOTION DECREASED

INSOMNIA

Skin And Subcutaneous Disorders - Other, Dry Skin Patches

URINARY URGENCY

Injury, Poisoning And Procedural Complications- Other, Scalp Laceration

Musculoskeletal And Connective Tissue Disorder - Other, Tendinitis

Skin And Subcutaneous Tissue Disorders - Other, Skin Color Change

Skin And Subcutaneous Tissue Disorders - Other: Blue Lips (Not Cyanosis)

HEMATURIA

RASH

Gastrointestinal Disorders - Other, Buccal Cyst

Investigations - Other, International Normalized Ration Increased

Infections And Infestations - Other, Gi Viral Infection

Gastrointestinal Disorders - Other, Dental Pain

Stomach Pain

SKIN INFECTION

HYPOMAGNESEMIA

Muscle Weakness Upper Limb

Skin And Subcutaneous Tissue Disorders- Other, Blister/Bug Bite On Finger

Skin And Subcutaneous Tissue Disorders- Other, Erythema

Neuropathy

Infections And Infestations - Other, Covid-19

Investigations - Other, Increased Mean Corpuscular Volume

DIFFICULTY WALKING, BACK PAIN, BOWEL/BLADDER URGENCY, LEGS GAVE OUT, AND PARESTHESIAS

Skin And Subcutaneous Tissue Disorders- Other, New Freckles/Moles

Surgical & Medical Procedures - Other, Dental Extractions

TENDONITIS

SINUS BRADYCARDIA

HYPERTHYROIDISM

Creatine Phosphokinase Increased

SUBJECT WAS ADMITTED TO THE HOSPITAL ON 10/24/20 WITH GRADE 2 WEIGHT LOSS THAT THE PHYSICIAN FELT NE

Skin And Subcutaneous Tissue Disorders- Other, Sore On Lips

Skin And Subcutaneous Tissue Disorders- Other, Transient Erythema

Musculoskeletal And Connective Tissue Disorders - Other, Extremity Cramps

Muscle Weakness Lower Limb

Urine Discoloration

SPINAL CORD COMPRESSION

ANEMIA

PARONYCHIA

BRUISING

HYPOALBUMINEMIA

Ear And Labyrinth Disorders - Other, Impacted Cerumen

Ear Pain

Elevated Amylase

Facial Pain

Gastrointestinal Disorders - Other, Stomatitis

Hoarseness

Laryngitis

Leg Pain

Localized Edema

Lung Infection

Metabolism And Nutrition Disorders - Other, Decreased Oral Intake

Metabolism Other - Decreased Vitamin D

Metbolism And Nutrition Disorders - Other, Hyperchloremia

Mucositis Oral

100%

80%

60%

40%

20%

Study treatment Arm

Cohort B

Cohort A

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Arm B (nivolumab, cabozantinib)Experimental Treatment8 Interventions

INDUCTION: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. TREATMENT: Patients with iuPD with clinical instability receive cabozantinib PO daily on days 1-28. Treatment repeats every 28 days until further disease progression or unacceptable toxicity. Patients with iCR receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients with non-CR/non-PD rwith clinical stability eceive nivolumab IV over 30 minutes on day 1 and cabozantinib PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI and blood and urine sample collection, and may also undergo a bone scan as clinically indicated throughout the study.

Group II: Arm A (nivolumab)Active Control8 Interventions

INDUCTION: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. TREATMENT: Patients with iuPD with clinical instability receive cabozantinib PO daily on days 1-28. Treatment repeats every 28 days until further disease progression or unacceptable toxicity Patients with iCR receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients with non-CR/non-PD with clinical stability receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI and blood and urine sample collection, and may also undergo a bone scan as clinically indicated throughout the study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Magnetic Resonance Imaging

2017

Completed Phase 3

~1180

Cabozantinib

2020

Completed Phase 2

~2360