What side effects are associated with this type of intervention?

Common treatments for melanoma, such as Cabozantinib (a tyrosine kinase inhibitor) and Pembrolizumab (a PD-1 inhibitor), are associated with several side effects. Cabozantinib can cause diarrhea, fatigue, nausea, decreased appetite, and hypertension. Pembrolizumab, an immune checkpoint inhibitor, may lead to immune-related adverse events including skin reactions, endocrine disorders, and less commonly, vitiligo and alopecia. Both treatments can result in serious adverse reactions, such as pneumonitis, colitis, and hepatitis, which may require discontinuation of therapy.

What prior FDA approvals exist?

Pembrolizumab, a PD-1 inhibitor, has received FDA approval for the treatment of advanced or metastatic melanoma, demonstrating significant improvements in progression-free and overall survival. It is used both as a monotherapy and in combination with other agents such as ipilimumab. Cabozantinib, a tyrosine kinase inhibitor, is being studied for its potential in melanoma treatment, although it is not yet a standard therapy for this condition. The combination of cabozantinib and pembrolizumab is currently under investigation to assess their combined safety and efficacy in advanced melanoma.

What other types of research exist?

Promising novel alternatives for melanoma treatment in 2024 include the combination of Nivolumab (a PD-1 inhibitor) and Ipilimumab (a CTLA-4 inhibitor), as well as the use of Talimogene Laherparepvec (T-VEC) combined with Pembrolizumab. These combinations have shown efficacy in clinical trials and represent potential options for patients seeking alternatives to Cabozantinib and Pembrolizumab.

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Tyrosine Kinase Inhibitor

Cabozantinib + Pembrolizumab for Melanoma

Phase 1 & 2

Waitlist Available

Led By Yousef Zakharia, MD

Research Sponsored by John Rieth

Eligibility Criteria Checklist

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

Must have

Aged 18 years and older

Histologically or cytologically confirmed unresectable in-transit (stage IIIc) or metastatic (stage IV) melanoma

Must not have

Patient has an active infection requiring systemic therapy

Patient requires concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up initiation of treatment up to 2 years

Awards & highlights

All Individual Drugs Already Approved

Approved for 5 Other Conditions

No Placebo-Only Group

Summary

This trial is testing a combination of two drugs to treat adults with advanced melanoma that cannot be surgically removed. One drug stops cancer cells from growing, and the other helps the immune system attack the cancer. The combination of pembrolizumab and ipilimumab is being tested for its effectiveness and safety in treating advanced melanoma.

Who is the study for?

Adults with advanced melanoma who can swallow pills, have measurable lesions, and haven't had certain treatments for their cancer recently. They must understand the study and agree to provide tissue samples. Women of childbearing age need a negative pregnancy test.

What is being tested?

The trial is testing the combination of two drugs, Cabozantinib and Pembrolizumab, to see how safe they are together and if they work well against advanced melanoma.

What are the potential side effects?

Possible side effects include immune system reactions that could affect organs, fatigue, skin changes, digestive issues like diarrhea or nausea, liver function changes, and potential increased risk of infections.

Eligibility Criteria

Inclusion Criteria

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

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I am 18 years old or older.

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My melanoma cannot be removed by surgery and is either stage IIIc or IV.

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I can provide previous biopsy samples for PD-L1 testing.

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I can swallow pills.

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I understand the study requirements and have signed the consent form.

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 infection.

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I need blood thinners or platelet inhibitors for my condition.

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I haven't had cancer treatment in the last 4 weeks or have recovered from its side effects.

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I had a severe allergic reaction to a specific cancer treatment before.

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I have been diagnosed with melanoma in the eye or mucous membranes.

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I have been treated with cabozantinib before.

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I have been diagnosed with HIV.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ initiation of treatment up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~initiation of treatment up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and initiation of treatment up to 2 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

Phase 1: Incidence of dose limiting toxicities using CTCAE, Version 4.03

Phase 2: Best overall response rate (ORR) (complete response (CR) + partial response (PR)) per RECIST v1.1

Secondary study objectives

Determine disease control rate (DCR) according to RECIST v1.1 criteria

Radiologic progression-free survival (PFS) per RECIST v1.1

Summarize overall survival (OS) with the method of Kaplan-Meier

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%

PALMAR-PLANTAR ERYTHRODYSESTHESIA SYNDROME

36%

HEADACHE

36%

PAIN IN EXTREMITY

36%

HYPERTENSION

32%

PROTEINURIA

32%

PAIN

27%

White Blood Cell Count Decreased

27%

ABDOMINAL PAIN

23%

Decreased Platelet Count

23%

PLATELET COUNT DECREASE

23%

HYPONATREMIA

23%

Platelet Count Decreased

23%

Skin Hypopigmentation

23%

Renal & Urinary Disorders - Other, Ketonuria

23%

HAIR COLOR CHANGE

18%

HEMOGLOBIN INCREASED

18%

HYPOKALEMIA

18%

Upper Respiratory Infection

18%

HYPOPHOSPHATEMIA

18%

Alopecia

18%

Hyperkalemia

14%

Rash Acneiform

14%

Pruritis

14%

Rash Maculopapular

14%

HYPOGLYCEMIA

14%

HYPERGLYCEMIA

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

Papulopustular Rash

ALKALINE PHOSPHATASE INCREASED

LIPASE INCREASED

Creatinine Increased

Back Pain

ABSOLUTE NEUTROPHIL COUNT DECREASED

Paresthesia

TUMOR PAIN

Skin And Subcutaneous Tissue Disorders- Other, Rash Unspecified

ORAL PAIN

LYMPHOCYTE COUNT DECREASED

NASAL CONGESTION

WEIGHT GAIN

HYPOCALCEMIA

DRY SKIN

Gastrointestinal Disorders - Other, Buccal Cyst

Allergic Rhinitis

Hypotension

Muscle Weakness Lower Limb

Skin And Subcutaneous Tissue Disorders- Other, Sore On Lips

Musculoskeletal And Connective Tissue Disorders - Other, Extremity Cramps

Skin And Subcutaneous Disorders - Other, Dry Skin Patches

Hypertension

SERUM AMYLASE INCREASED

Behaviour Disturbance

Investigations - Other, Eosinophilia

Sore Throat

JOINT RANGE OF MOTION DECREASED

Joint Range Of Motion Decreased

HEMATURIA

ANXIETY

Hypermagnesemia

Rash Ezcematoid

Musculoskeletal And Connective Tissue Disorder - Other, Tendinitis

Scalp Pain

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

Psychiatric Disorders - Other, Mood Swings

URINARY URGENCY

Sinus Tachycardia

Periodontal Disease

Peripheral Sensory Neuropathy

Scalp Lesion

Myalgia

Tooth Infection

RASH

Gastrointestinal Disorders - Other, Dental Pain

Peripheral Motor Neuropathy

Tachycardia

URINARY FREQUENCY

Conjunctivitis

Neuropathy

Sinusitis

Syncope

Activated Partial Thromboplastin Time Prolonged

Breast Pain

INSOMNIA

Infections And Infestations - Other, Gi Viral Infection

Stomach Pain

TENDONITIS

SKIN INFECTION

HYPOMAGNESEMIA

Muscle Weakness Upper Limb

Skin And Subcutaneous Tissue Disorders - Other, Skin Color Change

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

Surgical & Medical Procedures - Other, Dental Extractions

Investigations - Other, International Normalized Ration Increased

Skin And Subcutaneous Tissue Disorders- Other, Erythema

Infections And Infestations - Other, Covid-19

Investigations - Other, Increased Mean Corpuscular Volume

Skin And Subcutaneous Tissue Disorders- Other, Transient Erythema

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

Injury, Poisoning And Procedural Complications - Other, Ankle Injury

Injury, Poisoning And Procedural Complications- Other, Scalp Laceration

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

SINUS BRADYCARDIA

HYPERTHYROIDISM

Creatine Phosphokinase Increased

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

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

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Cabozantinib and pembrolizumabExperimental Treatment2 Interventions

Cabozantinib will be administered in the tablet form, at three dose levels: 40, 20 and 60 mg per day. Pembrolizumab will be administered as an intravenous infusion at a fixed dose of 200 mg once every 3 weeks.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cabozantinib

FDA approved

Pembrolizumab

FDA approved

0 / 12Eligibility 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

Melanoma treatments often involve Tyrosine Kinase Inhibitors (TKIs) and PD-1 inhibitors. TKIs, such as Cabozantinib, work by blocking specific enzymes (tyrosine kinases) that promote cancer cell growth and survival, thereby inhibiting tumor progression. PD-1 inhibitors, like Pembrolizumab, 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. These mechanisms are crucial for melanoma patients as they target the cancer cells directly and boost the body's immune response, offering a multifaceted approach to controlling and potentially eradicating the disease.