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 2023 Phase 2 trial • 25 Patients • NCT03680521

86%

Hypertension

71%

Dysphonia

57%

Headache

43%

Fatigue

43%

Constipation

43%

Lipase increased

43%

Oral dysaesthesia

29%

Blood thyroid stimulating hormone increased

29%

Pain

29%

Hypothyroidism

29%

Vomiting

29%

Diarrhoea

29%

Hypotension

29%

Myalgia

29%

Urinary tract infection

29%

Amylase increased

14%

Chills

14%

Herpes zoster

14%

Acute respiratory failure

14%

Flank pain

14%

Cough

14%

Alanine aminotransferase increased

14%

Epistaxis

14%

Night sweats

14%

Weight decreased

14%

Abdominal pain

14%

Arthralgia

14%

Hyperuricaemia

14%

Memory impairment

14%

Musculoskeletal pain

14%

Nasal congestion

14%

Urinary retention

14%

Nausea

14%

Rash

14%

Decreased appetite

14%

Dizziness

14%

Haematuria

14%

Nail discolouration

14%

Hypoglycaemia

14%

Oral herpes

14%

Pain in jaw

14%

Pneumonitis

14%

Procedural pain

14%

Pyrexia

14%

Rhinitis allergic

14%

Rhinorrhoea

14%

Sinus congestion

14%

Somnolence

14%

Thrombocytopenia

14%

Tinnitus

14%

Tooth abscess

14%

Urosepsis

14%

Atrial fibrillation

100%

80%

60%

40%

20%

Study treatment Arm

Sitravatinib 120 mg

Sitravatinib 80 mg

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

~3070

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.