What side effects are associated with this type of intervention?

The most common treatments for Uveal Melanoma, such as Lenvatinib (a Tyrosine Kinase Inhibitor) and Pembrolizumab (a PD-1 Inhibitor), are associated with several side effects. Lenvatinib can cause hypertension, proteinuria, and gastrointestinal issues, while Pembrolizumab is known for immune-related adverse events including skin reactions, endocrine disorders, and pneumonitis. Patients undergoing these treatments should be closely monitored for these potential side effects.

What prior FDA approvals exist?

As of now, there are no specific FDA approvals for the combination of Lenvatinib (a Tyrosine Kinase Inhibitor) and Pembrolizumab (a PD-1 Inhibitor) specifically for the treatment of Uveal Melanoma. However, these drugs have been approved for other types of cancers. Pembrolizumab is approved for various cancers including melanoma, while Lenvatinib is approved for thyroid cancer, renal cell carcinoma, and hepatocellular carcinoma. Their combination is currently being studied for efficacy in treating metastatic uveal melanoma.

What other types of research exist?

Promising novel alternatives for Uveal Melanoma patients include: 1) Tebentafusp, a bispecific protein targeting gp100 and CD3, which has shown improved overall survival in clinical trials. 2) IMCgp100, another bispecific T cell receptor therapy targeting gp100. 3) Combination therapies involving immune checkpoint inhibitors such as Ipilimumab (CTLA-4 inhibitor) with Nivolumab (PD-1 inhibitor) have also shown potential. These alternatives offer different mechanisms of action and may provide new hope for patients with metastatic uveal melanoma.

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Tyrosine Kinase Inhibitor

Lenvatinib + Pembrolizumab for Uveal Melanoma

Phase 2

Recruiting

Led By Matthew Taylor, MD

Research Sponsored by Providence Health & Services

Eligibility Criteria Checklist

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

Must have

Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated

Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

Must not have

Has an active infection requiring systemic therapy

Significant cardiovascular impairment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 30 days after last treatment dose

Awards & highlights

All Individual Drugs Already Approved

Approved for 10 Other Conditions

No Placebo-Only Group

Summary

This trial is testing a combination of two drugs, lenvatinib and pembrolizumab, to treat adults with metastatic uveal melanoma. Lenvatinib is taken as a daily pill, and pembrolizumab is given through an IV periodically. The goal is to see if these drugs can stop cancer growth and help the immune system fight the cancer. Pembrolizumab is an immune checkpoint inhibitor that has shown promise in treating various cancers, including melanoma, by enhancing the immune system's ability to fight cancer.

Who is the study for?

This trial is for adults with a confirmed diagnosis of metastatic uveal melanoma who haven't been treated with certain immune therapies before. Participants must have measurable disease, provide tissue samples, and have good organ function and performance status. They should agree to use contraception and not be pregnant or breastfeeding.

What is being tested?

The study tests the effectiveness of combining lenvatinib with pembrolizumab in treating metastatic uveal melanoma. It aims to see how well these drugs work together for patients who haven't received similar treatments previously.

What are the potential side effects?

Potential side effects include reactions related to the immune system, such as inflammation in various organs; skin issues; fatigue; liver problems; thyroid dysfunction; digestive disturbances; and an 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 have provided a sample of my tumor that has not been treated with radiation.

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I am fully active or can carry out light work.

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I am 18 or older with a confirmed diagnosis of metastatic uveal melanoma.

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I am not pregnant, not breastfeeding, and follow the birth control guidelines.

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 have a serious heart condition.

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I have received an organ or tissue transplant from another person.

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My blood pressure is not well-controlled.

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I have a bleeding or clotting disorder, or I'm at high risk for severe bleeding.

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I am not pregnant or breastfeeding.

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I have been treated with specific immune therapy for cancer.

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I have an immune system disorder or am on long-term steroids.

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I have an autoimmune disease treated with medication in the last 2 years.

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I have or had lung inflammation that needed steroids.

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I have active brain metastases or cancer in the lining of my brain.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 30 days after last treatment dose

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~30 days after last treatment dose

This trial's timeline: 3 weeks for screening, Varies for treatment, and 30 days after last treatment dose for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Evaluate the effect of lenvatinib plus pembrolizumab on progression free survival

Secondary study objectives

Therapeutic procedure

Evaluate the safety and tolerability of treatment with lenvatinib plus pembrolizumab in patients with metastatic uveal melanoma

Side effects data

From 2019 Phase 3 trial • 392 Patients • NCT01321554

70%

Diarrhoea

69%

Hypertension

57%

Decreased appetite

54%

Weight decreased

49%

Nausea

44%

Fatigue

40%

Headache

38%

Proteinuria

38%

Vomiting

38%

Stomatitis

33%

Palmar-plantar erythrodysaesthesia syndrome

33%

Arthralgia

33%

Dysphonia

32%

Constipation

30%

Cough

26%

Asthenia

25%

Oedema peripheral

21%

Rash

20%

Back pain

20%

Myalgia

19%

Abdominal pain

18%

Dysgeusia

18%

Abdominal pain upper

18%

Pain in extremity

18%

Musculoskeletal pain

18%

Dry mouth

18%

Dyspnoea

17%

Dizziness

16%

Pyrexia

16%

Oropharyngeal pain

16%

Hypokalaemia

15%

Dyspepsia

15%

Hypocalcaemia

14%

Epistaxis

13%

Dysphagia

13%

Alopecia

12%

Anaemia

12%

Musculoskeletal chest pain

12%

Dry skin

11%

Urinary tract infection

11%

Nasopharyngitis

10%

Oral pain

10%

Thrombocytopenia

10%

Hypoalbuminaemia

10%

Blood creatinine increased

10%

Electrocardiogram QT prolonged

10%

Upper respiratory tract infection

Dehydration

Neck pain

Depression

Hypomagnesaemia

Influenza like illness

Muscle spasms

Lymphopenia

Alanine aminotransferase increased

Muscular weakness

Malaise

Haematuria

Ejection fraction decreased

Pruritus

Hyponatraemia

Blood thyroid stimulating hormone increased

Platelet count decreased

Aspartate aminotransferase increased

Toothache

Glossodynia

Blood alkaline phosphatase increased

Hyperkeratosis

Bronchitis

Flatulence

Influenza

Dysuria

Anxiety

Hyperglycaemia

Leukopenia

Non-cardiac chest pain

Productive cough

Paraesthesia

Hypothyroidism

Haemoptysis

White blood cell count decreased

Pneumonia

General physical health deterioration

Sepsis

Cholecystitis

Pulmonary embolism

Malignant pleural effusion

seizure

Acute myocardial infarction

Atrial fibrillation

Lower respiratory tract infection

Hypotension

Lung infection

Spinal cord compression

Acute kidney injury

Blood uric acid increased

Monoparesis

Acute respiratory failure

Hypercalcaemia

Hepatic failure

Appendicitis

Death

Respiratory failure

Osteoarthritis

Intestinal obstruction

Small intestinal obstruction

Intracranial tumour haemorrhage

Acute coronary syndrome

Colitis

Transient ischaemic attack

Pancreatitis

Atrial flutter

Cardio-respiratory arrest

Uterine prolapse

Coronary artery stenosis

Pneumatosis intestinalis

Cerebrovascular accident

Confusional state

Liver injury

Diverticulitis

Bacteraemia

Gastroenteritis

Perineal abscess

Wound infection

Malignant neoplasm progression

Bone pain

Cancer pain

Syncope

Vocal cord paralysis

Nephrotic syndrome

100%

80%

60%

40%

20%

Study treatment Arm

Randomization Phase: Lenvatinib 24 mg

Randomization Phase: Placebo

OOL, Treatment Period: Lenvatinib 24 mg

OOL, Treatment Period: Lenvatinib 20 mg

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 10 Other Conditions

This treatment demonstrated efficacy for 10 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: Pembrolizumab + LenvatinibExperimental Treatment2 Interventions

Lenvatinib 20 mg daily plus pembrolizumab 200 mg IV every 3 weeks.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

FDA approved

Lenvatinib

FDA approved

0 / 15Eligibility 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

Lenvatinib, a Tyrosine Kinase Inhibitor (TKI), blocks enzymes involved in tumor growth and angiogenesis, while Pembrolizumab, a PD-1 inhibitor, enhances the immune system's ability to detect and destroy cancer cells by blocking the PD-1 pathway. These mechanisms are important for Uveal Melanoma patients as they offer a multi-faceted approach to targeting cancer cells, potentially improving treatment efficacy and outcomes.