What side effects are associated with this type of intervention?

Common treatments for Renal Cell Carcinoma, such as Tyrosine Kinase Inhibitors (e.g., Sitravatinib), PD-1 inhibitors (e.g., Nivolumab), and CTLA-4 inhibitors (e.g., Ipilimumab), have distinct side effect profiles. TKIs often cause hypertension, diarrhea, fatigue, and hand-foot syndrome. PD-1 inhibitors can lead to immune-related adverse events like skin reactions, endocrine disorders, and pneumonitis. CTLA-4 inhibitors are associated with colitis, hepatitis, and endocrinopathies. When these treatments are combined, the frequency and severity of side effects can increase, requiring careful monitoring and management.

What prior FDA approvals exist?

The FDA has approved several treatments for Renal Cell Carcinoma (RCC) that involve tyrosine kinase inhibitors (TKIs), PD-1 inhibitors, and CTLA-4 inhibitors. Nivolumab, a PD-1 inhibitor, has been approved for use in combination with Ipilimumab, a CTLA-4 inhibitor, for the first-line treatment of advanced RCC. Additionally, combinations of TKIs such as Axitinib with PD-1 inhibitors like Pembrolizumab have also received FDA approval for RCC treatment. These combinations aim to enhance anti-tumor activity by targeting different pathways involved in cancer progression.

What other types of research exist?

Promising alternatives to Sitravatinib in combination with Nivolumab and Ipilimumab for RCC patients include: 1) Lenvatinib plus Pembrolizumab, which has shown high objective response rates (ORR) and complete response (CR) rates, particularly for patients with symptomatic or life-threatening disease burden. 2) Nivolumab plus Cabozantinib, which also demonstrates high ORR and is suitable for patients requiring rapid treatment response. Both combinations are supported by clinical trial data and are likely to be considered effective treatment options in 2024.

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Checkpoint Inhibitor

Sitravatinib + Immunotherapy for Renal Cell Carcinoma

Phase 1

Waitlist Available

Research Sponsored by Mirati Therapeutics Inc.

Eligibility Criteria Checklist

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

Must have

Confirmed diagnosis of Clear-Cell Renal Cell Carcinoma (for initial cohorts under consideration)

No prior treatment with systemic therapy (for initial cohorts under consideration)

Must not have

Known or suspected presence of other cancer

Brain metastases (for initial cohorts under consideration)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through study completion, an average of 12 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug combination of sitravatinib, nivolumab, and ipilimumab in patients with certain types of cancer. The goal is to see if this combination can effectively stop cancer growth and help the immune system fight the cancer.

Who is the study for?

This trial is for adults with advanced or metastatic clear-cell renal cell carcinoma (ccRCC) or other solid tumors who haven't had systemic therapy. They must have a confirmed diagnosis, good bone marrow and organ function, and no heart issues, other cancers, brain metastases, carcinomatous meningitis, immunocompromising conditions or autoimmune diseases.

What is being tested?

The study tests the combination of Sitravatinib with Nivolumab and Ipilimumab in treating ccRCC. It's an open-label Phase 1 trial that looks at safety, how well it works against cancer (clinical activity), and how the body processes these drugs (pharmacokinetics).

What are the potential side effects?

Possible side effects include immune-related reactions like inflammation in organs; skin rash; liver enzyme changes; endocrine disorders such as thyroid dysfunction; fatigue; gastrointestinal symptoms like diarrhea; and potential infusion-related reactions.

Eligibility Criteria

Inclusion Criteria

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

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I have been diagnosed with Clear-Cell Renal Cell Carcinoma.

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I have not had any systemic therapy for my condition.

Exclusion Criteria

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

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I may have another type of cancer besides the one being treated.

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My cancer has spread to my brain.

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I have cancer cells in the fluid around my brain and spinal cord.

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My heart does not function properly.

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I have or had an autoimmune disease.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through study completion, an average of 12 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through study completion, an average of 12 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and through study completion, an average of 12 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

Frequency of patients experiencing treatment-emergent AEs

Secondary study objectives

Duration of Response (DOR)

Objective Response Rate (ORR) in accordance with RECIST v1.1

Progression-free Survival (PFS)

Side effects data

From 2022 Phase 1 & 2 trial • 42 Patients • NCT03015740

87%

Anemia

87%

Hyperglycemia

87%

Hypertriglyceridemia

80%

Investigations - Other, specify

80%

Creatinine increased

80%

Weight loss

80%

Fatigue

73%

Diarrhea

73%

Anorexia

73%

Lipase increased

67%

Lymphocyte count decreased

67%

Serum amylase increased

67%

Proteinuria

67%

Cough

60%

Hypertension

53%

Abdominal pain

53%

Constipation

53%

Nausea

47%

Cholesterol high

47%

Vomiting

47%

Alanine aminotransferase increased

47%

Hyperkalemia

47%

Hoarseness

47%

Rash acneiform

47%

Back pain

40%

Pain

40%

Aspartate aminotransferase increased

40%

Hypoalbuminemia

40%

Dyspnea

40%

Mucositis oral

40%

Arthralgia

40%

Myalgia

33%

Metabolism and nutrition disorders - Other, specify

33%

Hyponatremia

33%

Hypophosphatemia

33%

INR increased

33%

Dizziness

33%

Headache

33%

Edema Limbs

33%

Activated partial thromboplastin time prolonged

33%

Alkaline phosphatase increased

33%

Hypomagnesemia

33%

Insomnia

33%

Postnasal drip

33%

Endocrine disorders - Other, specify

27%

Sinusitis

27%

Hypothyroidism

27%

Rash maculo-papular

27%

Skin and subcutaneous tissue disorders - Other, specify

27%

Hypocalcemia

20%

Allergic rhinitis

20%

Urinary frequency

20%

Anxiety

20%

Nasal congestion

20%

Wheezing

20%

Fever

20%

Bruising

20%

Dry skin

13%

Hypoglycemia

13%

Pruritus

13%

Non-cardiac chest pain

13%

Productive cough

13%

Flu like symptoms

13%

White blood cell decreased

13%

Ear pain

13%

Surgical and medical procedures - Other, specify

13%

Generalized muscle weakness

13%

Hypernatremia

13%

Vertigo

13%

Gastrointestinal disorders - Other, specify

13%

Pancreatitis

13%

Chills

13%

Cardiac disorders - Other, specify

13%

Blood bilirubin increased

13%

Hypokalemia

13%

Paresthesia

13%

Thromboembolic event

13%

Arthritis

13%

Urinary tract infection

13%

Atrial fibrillation

13%

Gait disturbance

13%

Platelet count decreased

13%

Renal and urinary disorders - Other, specify

13%

Sore throat

13%

Palmar-plantar erythrodysesthesia syndrome

Dry mouth

anemia

Gastroesophageal reflux disease

Fall

Erectile dysfunction

Hypersomnia

Watering eyes

Blurred vision

Irritability

Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify

Conjunctivitis

appendicitus

Hyperthyroidism

Oral dysesthesia

Urinary urgency

Respiratory, thoracic and mediastinal disorders - Other, specify

abodominal pain

Laryngeal hemorrhage

Upper gastrointestinal hemorrhage

Sinus tachycardia

Tinnitus

Hepatobiliary disorders - Other, specify

Infections and infestations - Other, specify

Seroma

Cardiac troponin I increased

Hemoglobin increased

Hypercalcemia

Concentration impairment

Nervous system disorders - Other, specify

Depression

Chronic kidney disease

Urinary retention

Epistaxis

Hyperhidrosis

Photosensitivity

Lymphocele

Bone pain

Muscle weakness lower limb

Neck pain

Pain in extremity

bronchial obsturction

Localized edema

Blood and lymphatic system disorders - Other, specify

Abdominal distension

Hematuria

Sneezing

Pain of skin

Phlebitis

Oral pain

Malaise

Dehydration

Hot flashes

100%

80%

60%

40%

20%

Study treatment Arm

Received Sitravatinib 80 mg in Combination With Nivolumab

Received Sitravatinib 120 mg in Combination With Nivolumab

Received Sitravatinib 150 mg in Combination With Nivolumab

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 1b Dose Escalation Cohort BExperimental Treatment3 Interventions

Patients with favorable-risk RCC with clear cell component for first-line treatment.

Group II: Phase 1b Dose Escalation Cohort AExperimental Treatment3 Interventions

Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment

Group III: Phase 1: Dose EscalationExperimental Treatment3 Interventions

Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ipilimumab

2015

Completed Phase 3

~3420

Sitravatinib

2017

Completed Phase 2

~510

Nivolumab

2015

Completed Phase 3

~4010

0 / 7Eligibility 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

The most common treatments for Renal Cell Carcinoma (RCC) include Tyrosine Kinase Inhibitors (TKIs), PD-1 inhibitors, and CTLA-4 inhibitors. TKIs, such as sitravatinib, block enzymes involved in the growth and spread of cancer cells by inhibiting pathways like VEGF, which is crucial for tumor angiogenesis. PD-1 inhibitors, like nivolumab, enhance the immune system's ability to detect and destroy cancer cells by blocking the PD-1 pathway, which tumors use to evade immune detection. CTLA-4 inhibitors, such as ipilimumab, further boost the immune response by blocking CTLA-4, a checkpoint that downregulates immune activity. These mechanisms are vital for RCC patients as they target both the tumor's growth and its ability to hide from the immune system, offering a comprehensive approach to treatment.

First-line Nivolumab plus Ipilimumab Versus Sunitinib in Patients Without Nephrectomy and With an Evaluable Primary Renal Tumor in the CheckMate 214 Trial.