What side effects are associated with this type of intervention?

Common treatments for lung cancer, such as tyrosine kinase inhibitors (e.g., cabozantinib) and immunotherapies (e.g., nivolumab), have distinct side effect profiles. Cabozantinib can cause hypertension, diarrhea, fatigue, and hand-foot syndrome. Nivolumab, an immune checkpoint inhibitor, is associated with immune-related adverse events including pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. Both treatments can lead to severe side effects that require careful monitoring and management by healthcare providers.

What prior FDA approvals exist?

Several FDA-approved treatments for lung cancer involve immunotherapy and tyrosine kinase inhibitors (TKIs). Nivolumab, an immunotherapy drug, has been approved for use in combination with other agents like ipilimumab for advanced non-small cell lung cancer (NSCLC). Pembrolizumab, another immunotherapy, has been approved in combination with chemotherapy for advanced NSCLC. Tyrosine kinase inhibitors such as cabozantinib are being studied in combination with immunotherapies like nivolumab, although specific FDA approvals for this combination in lung cancer are still under investigation. Other TKIs like osimertinib have been approved for specific genetic mutations in NSCLC.

What other types of research exist?

Promising alternatives to Cabozantinib and Nivolumab for lung cancer treatment include the combination of Atezolizumab with Bevacizumab and chemotherapy (as seen in the IMpower 150 trial), and Pembrolizumab combined with chemotherapy (as seen in the KEYNOTE-189 trial). These combinations have shown improved progression-free survival and overall survival in patients with advanced non-small cell lung cancer.

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Tyrosine Kinase Inhibitor

Cabozantinib + Nivolumab for Lung Cancer

Phase 2

Waitlist Available

Led By Joel W Neal

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

Creatinine =< 1.5 x ULN OR calculated or measured creatinine clearance >= 50 mL/min/1.73m^2

Patient must have radiographic and/or clinical progression following one line of platinum-based chemotherapy AND one line of prior checkpoint inhibitor immunotherapy

Must not have

Patients must not have specified cardiac, vascular, or thrombotic conditions

Patients must not have specified gastrointestinal, abdominal, or infectious conditions

Timeline

Screening 3 weeks

Treatment Varies

Follow Up every 6 weeks for the first year on study, and then every 12 weeks after year one

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing whether cabozantinib alone or with nivolumab is better than other treatments for patients with a type of lung cancer called non-squamous non-small cell lung cancer. Cabozantinib stops cancer cells from growing, while nivolumab helps the immune system fight the cancer. The goal is to see if these treatments can help patients live longer without their cancer getting worse.

Who is the study for?

This trial is for adults with non-squamous non-small cell lung cancer (NSCLC) who've had one round of platinum-based chemo and checkpoint inhibitor immunotherapy. They must have manageable side effects from past treatments, no major organ issues, can swallow pills, and have no severe heart conditions or untreated viral infections. Pregnant individuals or those planning to conceive are excluded.

What is being tested?

The study tests if cabozantinib alone or combined with nivolumab is more effective than standard chemotherapy in NSCLC treatment. Cabozantinib blocks enzymes needed for tumor growth; nivolumab boosts the immune system's cancer fight. Standard chemo drugs kill or stop cancer cells from growing.

What are the potential side effects?

Cabozantinib may cause liver problems, high blood pressure, mouth sores, hand-foot syndrome (redness and pain on palms/soles), and diarrhea. Nivolumab might lead to immune-related inflammation in organs like lungs or intestines, skin rash, fatigue, and infusion reactions.

Eligibility Criteria

Inclusion Criteria

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

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My kidney function, measured by creatinine levels or clearance, is within the required range.

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My cancer progressed after both platinum chemotherapy and immunotherapy.

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I finished my last chemotherapy before the specified time.

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I had hepatitis C but have been treated and cured.

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My tumor does not have EGFR mutations or ALK rearrangements.

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My lung cancer is non-squamous non-small cell type.

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I have not had VEGFR-targeted therapy before.

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My cancer has spread to distant parts of my body.

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I have HIV, am on treatment, and my viral load is undetectable.

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I have chosen a chemotherapy plan for my treatment and haven't used this chemotherapy for metastatic disease before.

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My tumor does not have EGFR mutations or ALK rearrangements.

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I have recovered from side effects of my previous treatment.

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My heart function is classified as class 2B or better according to NYHA.

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I am 18 years old or older.

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I have no ongoing issues from previous radiation treatments.

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I've had one round of chemotherapy and one round of immunotherapy for my cancer.

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I am able to get out of my bed or chair and move around.

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I have HIV, am on treatment, and my viral load is undetectable.

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

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My cancer has grown after at least 2 treatment cycles.

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I have chronic hepatitis B but my viral load is undetectable.

Exclusion Criteria

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

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I do not have any heart, blood vessel, or clotting disorders.

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I do not have any serious stomach, gut, or infection issues.

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My cancer has not spread to my brain or spinal cord.

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I haven't had lung inflammation caused by drugs in the last 3 months.

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I haven't had serious stomach or intestinal bleeding in the last 6 months.

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I do not have an active or known history of autoimmune disease.

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I haven't coughed up a significant amount of blood recently.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ every 6 weeks for the first year on study, and then every 12 weeks after year one

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~every 6 weeks for the first year on study, and then every 12 weeks after year one

This trial's timeline: 3 weeks for screening, Varies for treatment, and every 6 weeks for the first year on study, and then every 12 weeks after year one for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Progression-free survival (PFS) for patient population with non-squamous no-small cell lung cancer (NSCLC)

Secondary study objectives

Best objective response for each arm

Upper arm

Toxicity profile of monotherapy with cabozantinib, and the combination of nivolumab and cabozantinib

Other study objectives

Agreement between central view and site review in terms of progression-free survival

Correlative biomarker research

The RECIST1.1 response at each time point

Side effects data

From 2019 Phase 2 trial • 13 Patients • NCT02315430

85%

Fatigue

77%

Nausea

62%

Dysgeusia

62%

Vomiting

54%

Alkaline Phosphatase Increased

54%

Aspartate Aminotransferase Increased

54%

Mucositis Oral

54%

Abdominal Pain

46%

Hypertension

46%

Anorexia

38%

Alanine Aminotransferase Increased

38%

Thromboembolic Event

38%

Anemia

38%

Diarrhea

38%

Constipation

38%

Cough

38%

Weight Loss

38%

Dyspnea

31%

Hypomagnesemia

31%

Back Pain

31%

Lipase Increased

31%

Hypoalbuminemia

23%

Hypophosphatemia

23%

Hyperglycemia

23%

Dizziness

23%

Palmar-Plantar Erythrodysesthesia Syndrome

23%

Alopecia

23%

Hypothyroidism

23%

Pain In Extremity

23%

Oral Pain

23%

Pain

23%

Headache

15%

Sore Throat

15%

Activated Partial Thromboplastin Time Prolonged

15%

Myalgia

15%

Bloating

15%

White Blood Cell Decreased

15%

Insomnia

15%

Dry Mouth

15%

Dyspepsia

15%

Dehydration

15%

Hypocalcemia

15%

Dry Skin

15%

Flushing

15%

Peripheral Sensory Neuropathy

15%

Abdominal Distension

15%

Platelet Count Decreased

Allergic Rhinitis

Generalized Muscle Weakness

Creatinine Increased

Hyponatremia

Flank Pain

Bone Pain

Gastroesophageal Reflux Disease

Chest Pain - Cardiac

Vertigo

Neutrophil Count Decreased

Arthralgia

Syncope

Proteinuria

Pleural Effusion

Nasal Congestion

Pleuritic Pain

Hoarseness

Nail Discoloration

Ventricular Tachycardia

Tinnitus

Gastrointestinal Pain

Floaters

Dysphagia

Blood Bilirubin Increased

Lung Infection

Fever

Depression

Hypersomnia

Hypotension

Productive Cough

Memory Impairment

Anxiety

Cardiac Troponin I Increased

Urinary Incontinence

Pancreatitis

Upper Respiratory Infection

Bruising

Weight Gain

Skin Induration

100%

80%

60%

40%

20%

Study treatment Arm

Cabozantinib

Awards & Highlights

No Placebo-Only Group

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

Trial Design

4Treatment groups

Experimental Treatment

Active Control

Group I: Step 2, Arm Z (cabozantinib S-malate, nivolumab)Experimental Treatment5 Interventions

Patients in Step 2, Arm Z receive cabozantinib S-malate PO QD and nivolumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may continue to receive therapy after investigator-assessed RECIST 1.1 defined progression, including stable clinical and performance status and have potential for continued clinical benefit. Patients also undergo ECHO as clinically indicated, CT throughout the trial, and collection of blood on study.

Group II: Step 1, Arm B (cabozantinib S-malate, nivolumab)Experimental Treatment5 Interventions

Patients in Step 1, Arm B receive cabozantinib S-malate PO QD and nivolumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may continue to receive therapy after investigator-assessed RECIST 1.1 defined progression, including stable clinical and performance status and have potential for continued clinical benefit. Patients also undergo ECHO as clinically indicated, CT throughout the trial, and collection of blood on study.

Group III: Step 1, Arm A (cabozantinib S-malate)Experimental Treatment4 Interventions

Patients in Step 1, Arm A receive cabozantinib S-malate PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may continue to receive therapy after investigator-assessed RECIST 1.1 defined progression, including stable clinical and performance status and have potential for continued clinical benefit. Patients also undergo ECHO as clinically indicated, CT throughout the trial, and collection of blood on study.

Group IV: Step 1, Arm C (standard chemotherapy)Active Control8 Interventions

Patients in Step 1, Arm C receive ramucirumab IV over 30-60 minutes and docetaxel IV over 1 hour on day 1, or docetaxel IV over 1 hour on days 1 and 8, or gemcitabine hydrochloride IV on days 1 and 8, or paclitaxel IV over 3 hours on day 1, or nab-paclitaxel IV over 30 minutes on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity and at the discretion of the treating physician. Patients also undergo ECHO as clinically indicated, CT throughout the trial, and collection of blood on study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biospecimen Collection

2004

Completed Phase 3

~2030

Cabozantinib S-malate

2013

Completed Phase 2

~590

Computed Tomography

2017

Completed Phase 2

~2790

Echocardiography

2013

Completed Phase 4

~11580

Nivolumab

2015

Completed Phase 3

~4010

0 / 28Eligibility 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

Tyrosine Kinase Inhibitors (TKIs) like Cabozantinib block enzymes involved in cancer cell growth, effectively halting their proliferation. Immunotherapy agents such as Nivolumab enhance the immune system's ability to detect and destroy cancer cells by inhibiting proteins that allow cancer to evade immune detection. These mechanisms are vital for lung cancer patients as they guide the selection of targeted treatments, improving the chances of effective management and enhancing quality of life.

A Review of Recent Advances in the Treatment of Elderly and Poor Performance NSCLC.The management of non-small-cell lung cancer: a case history.