What side effects are associated with this type of intervention?

Common treatments for kidney cancer, such as the combination of Nivolumab (PD-1 inhibitor) and Ipilimumab (CTLA-4 inhibitor), often lead to immune-related adverse events. These include fatigue, rash, diarrhea, and liver enzyme abnormalities. More severe side effects can involve pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. These side effects occur because the drugs enhance the immune system's ability to attack cancer cells, which can also result in the immune system attacking normal tissues.

What prior FDA approvals exist?

Nivolumab, a PD-1 inhibitor, and Ipilimumab, a CTLA-4 inhibitor, have been approved by the FDA for the treatment of advanced renal cell carcinoma (RCC). The combination of these two immunotherapies has shown efficacy in clinical trials, such as CheckMate 214, where they were compared to sunitinib, a VEGFR inhibitor. This combination is known for providing durable long-term responses and is often preferred for patients seeking a treatment-free interval or curative intent. Other related drugs that have been approved for RCC include pembrolizumab (another PD-1 inhibitor) often used in combination with axitinib (a VEGFR inhibitor), as seen in the KEYNOTE-426 trial.

What other types of research exist?

Promising alternatives to Nivolumab and Ipilimumab for kidney cancer patients include: <ol> <li>Pembrolizumab plus Axitinib: This combination has shown efficacy in the KEYNOTE-426 trial.</li> <li></li> </ol> Atezolizumab plus Bevacizumab: Demonstrated positive outcomes in the IMmotion151 trial. 3. Lenvatinib plus Pembrolizumab: Evaluated in the CLEAR study with favorable results. 4. Nivolumab plus Cabozantinib: Shown to be effective in the CheckMate 9ER trial.

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Checkpoint Inhibitor

Nivolumab + Ipilimumab Timing for Kidney Cancer

Phase 2

Waitlist Available

Led By Toni K Choueiri, MD

Research Sponsored by Toni Choueiri, MD

Eligibility Criteria Checklist

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

Must have

Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 28 days prior to first study treatment

Unresectable advanced or metastatic RCC to include both clear cell and non-clear histologies

Must not have

Serious, non-healing or dehiscing wound or active ulcer

History of idiopathic pulmonary fibrosis, organized pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening imaging CT of the chest. History of radiation pneumonitis in the radiation field is permitted

Timeline

Screening 3 weeks

Treatment Varies

Follow Up after initiation of arm b treatment, patients underwent imaging at 12 weeks and then every 8 weeks, up to 22 months.

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing two drugs, Nivolumab and Ipilimumab, to treat advanced kidney cancer. These drugs help the immune system fight cancer cells. The study aims to find better treatment strategies for patients who do not respond well to standard treatments. Nivolumab and Ipilimumab have been used in combination to treat various cancers, including metastatic melanoma and advanced renal cell carcinoma, showing promising results in improving patient outcomes.

Who is the study for?

This trial is for adults with advanced kidney cancer, including those who haven't had their cancer surgically removed or have metastatic RCC. Participants can be new or previously treated but not with certain immune checkpoint inhibitors. They must have measurable disease, good organ function, and provide a tissue sample. Women of childbearing age need a negative pregnancy test and agree to use contraception.

What is being tested?

The OMNIVORE Study is testing the timing and effectiveness of two drugs, Nivolumab and Ipilimumab, in treating advanced renal cell carcinoma (RCC). The study aims to optimize how these drugs are administered based on patient response to treatment.

What are the potential side effects?

Potential side effects include immune-related reactions that may affect organs like the liver or lungs, skin rash, hormone gland problems (like thyroid), infusion reactions during drug administration, fatigue, and possible increased risk of infections.

Eligibility Criteria

Inclusion Criteria

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

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My recent tests show my organs are functioning well.

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My kidney cancer cannot be removed by surgery and has spread.

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My stored cancer tissue sample is good enough for testing.

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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 a serious wound or ulcer that is not healing.

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I have a history of lung scarring or inflammation but not from radiation.

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I have tested positive for HIV/AIDS.

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All side effects from my previous cancer treatments have improved to mild or returned to normal.

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I have signs of a blocked gut or need nutrition through IV.

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My adrenal gland disorder is not under control.

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I have not received a live vaccine in the last 4 weeks.

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I haven't had severe infections or been hospitalized for them in the last 4 weeks.

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I have had a stem cell or organ transplant in the past.

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I do not have severe heart problems like recent heart attacks or unstable heart rhythms.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ after initiation of arm b treatment, patients underwent imaging at 12 weeks and then every 8 weeks, up to 22 months.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~after initiation of arm b treatment, patients underwent imaging at 12 weeks and then every 8 weeks, up to 22 months.

This trial's timeline: 3 weeks for screening, Varies for treatment, and after initiation of arm b treatment, patients underwent imaging at 12 weeks and then every 8 weeks, up to 22 months. for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Percentage of Subjects With Persistent Partial Response (PR) or Complete Response (CR) at 1 Year Since Nivolumab Discontinuation (Arm A Only)

Percentage of Subjects With Stable or Progressive Disease (SD/PD) to Nivolumab Induction That Convert to Complete or Partial Response (CR/PR) Upon the Addition of Ipilimumab to Nivolumab (Arm B Only)

Secondary study objectives

18-month Overall Survival Rate From Initiation of Nivolumab Induction (Overall Cohort)

Immune Related Objective Response Rate (irORR) in Arm A and Arm B

Median Progression Free Survival (Arm B)

+6 more

Side effects data

From 2024 Phase 3 trial • 529 Patients • NCT02017717

80%

Fatigue

70%

Diarrhoea

70%

Headache

40%

Vomiting

40%

Aspartate aminotransferase increased

40%

Rash maculo-papular

40%

Alanine aminotransferase increased

40%

Lipase increased

30%

Partial seizures

30%

Hemiparesis

30%

Gait disturbance

30%

Fall

30%

Cough

30%

Dry skin

30%

Amylase increased

30%

Nausea

30%

Confusional state

20%

Malignant neoplasm progression

20%

Pyrexia

20%

Candida infection

20%

Mucosal infection

20%

Decreased appetite

20%

Back pain

20%

Dysphonia

20%

Hypotension

20%

Colitis

20%

Hyperthyroidism

20%

Oedema peripheral

20%

Muscular weakness

20%

Hypothyroidism

10%

Tinnitus

10%

Cushingoid

10%

Diabetic ketoacidosis

10%

Procedural haemorrhage

10%

Blood bilirubin increased

10%

Bradycardia

10%

Sinus tachycardia

10%

Hyperglycaemia

10%

Hypocalcaemia

10%

Neck pain

10%

Brain oedema

10%

Hydrocephalus

10%

Lethargy

10%

Seizure

10%

Hypertension

10%

Palpitations

10%

Cheilitis

10%

Presyncope

10%

Face oedema

10%

Oedema

10%

Conjunctivitis

10%

Enterocolitis infectious

10%

Oral candidiasis

10%

Pneumonia

10%

Sinusitis

10%

Staphylococcal infection

10%

Blood alkaline phosphatase increased

10%

Spinal pain

10%

Tremor

10%

Dizziness

10%

Dysarthria

10%

Urinary retention

10%

Dyspnoea exertional

10%

Nasal congestion

10%

Pneumonitis

10%

Dermatitis

10%

Erythema

10%

Rash

10%

Klebsiella infection

10%

Hypomagnesaemia

10%

Syncope

10%

Haemorrhage intracranial

10%

Pancreatitis

10%

Cholecystitis

10%

Upper respiratory tract infection

10%

Acute kidney injury

10%

Dermatitis bullous

10%

Lymphopenia

10%

Optic nerve disorder

10%

Visual impairment

10%

Dehydration

10%

Hypokalaemia

10%

Scoliosis

10%

Cognitive disorder

10%

Memory impairment

10%

Hallucination

10%

Insomnia

10%

Irritability

10%

Urinary incontinence

10%

Dyspnoea

10%

Dermatitis acneiform

10%

Pelvic venous thrombosis

10%

Sepsis

100%

80%

60%

40%

20%

Study treatment Arm

Cohort 1: Arm N1+I3

Cohort 2: Arm B

Part A Cohort 1c: Arm N3+RT+TMZ

Part A Cohort 1d: Arm N3+RT

Part B Cohort 1c: Arm N3+RT+TMZ

Part B Cohort 1d: Arm N3+RT

Cohort 1: Arm N3

Cohort 1b: Arm N3+I1

Cohort 2: Arm N3

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: Overall cohort: Initial Primary Treatment with Nivolumab (induction phase)Experimental Treatment1 Intervention

* Therapy with nivolumab IV every 2 weeks * Serial imaging assessments every 8 weeks * After confirmatory scans, patients are assigned to Arm A or Arm B.

Group II: Arm B: Nivolumab+Ipilimumab then nivolumab alone (for patients with SD/PD to induction nivolumab)Experimental Treatment2 Interventions

Patients with confirmed SD/PD to induction nivolumab are allocated to Arm B (Combination Therapy Arm). * In combination therapy, patients received nivolumab 3 mg/kg and ipilimumab 1 mg/kg intravenously every 3 weeks for two doses. * After then nivolumab will be continued at 480 mg IV every 4 weeks until disease progression. * Arm B patients undergo imaging at 12 weeks and then every 8 weeks.

Group III: Arm A: Observation Arm (for patients with persistent response to induction nivolumab)Experimental Treatment2 Interventions

Patients with persistent response (complete or partial response) to induction nivolumab are assigned to Arm A (Observation Arm). * Patients discontinued nivolumab after allocation to Arm A. * Serial imaging assessments every 8 weeks. * If scans persistently show PR/CR, patients remained on observation. * If progressive disease develops, therapy with nivolumab (480 mg IV every 4 weeks) will be resumed. * If there is subsequent progression on nivolumab monotherapy, ipilimumab (1 mg/kg IV every 3 weeks x 2 doses) is added. * If progression after nivolumab + ipilimumab, therapy discontinued. If SD/PR/CR, nivolumab is continued until progression.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ipilimumab

2015

Completed Phase 3

~3070

Nivolumab

2015

Completed Phase 3

~4010

0 / 14Eligibility 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

Nivolumab (a PD-1 inhibitor) and Ipilimumab (a CTLA-4 inhibitor) are immune checkpoint inhibitors used in the treatment of kidney cancer. Nivolumab blocks the PD-1 pathway, which cancer cells exploit to avoid detection by the immune system, thereby enhancing the body's immune response against cancer cells. Ipilimumab blocks CTLA-4, another checkpoint that downregulates immune responses, further boosting the immune system's ability to fight cancer. These mechanisms are crucial for kidney cancer patients as they can lead to improved overall survival and higher rates of durable complete responses, offering a significant therapeutic advantage over traditional treatments.