What side effects are associated with this type of intervention?

The combination of Lenvatinib and Pembrolizumab for treating Oral Squamous Cell Carcinoma can lead to several side effects. Common adverse events include hypertension, diarrhea, weight loss, proteinuria, and palmar-plantar erythrodysesthesia syndrome. Pembrolizumab, as an immune checkpoint inhibitor, can also cause immune-related adverse events such as skin rash, colitis, hepatitis, endocrinopathies, and pneumonitis. These side effects should be carefully monitored and managed by healthcare providers.

What prior FDA approvals exist?

For the treatment of Oral Squamous Cell Carcinoma (OSCC), the FDA has approved several drugs that target similar pathways to Lenvatinib and Pembrolizumab. Pembrolizumab itself is FDA-approved for head and neck squamous cell carcinoma (HNSCC), including OSCC, particularly for patients who have progressed after platinum-based chemotherapy. Another similar drug is Nivolumab, an anti-PD-1 monoclonal antibody, which is also approved for recurrent or metastatic HNSCC. Cetuximab, an anti-EGFR monoclonal antibody, is another FDA-approved treatment for HNSCC, often used in combination with chemotherapy. These treatments enhance the immune system's ability to fight cancer or target specific growth factor receptors involved in tumor growth.

What other types of research exist?

Promising novel alternatives to Lenvatinib + Pembrolizumab for Oral Squamous Cell Carcinoma patients include: 1) Pembrolizumab plus Cetuximab, which has shown a 45% overall response rate in treatment-refractory metastatic HNSCC. 2) Metronomic chemotherapy, which uses frequent, lower doses of chemotherapy to target tumor angiogenesis and minimize toxicity. 3) Farnesyltransferase inhibitors like tipifarnib, which have demonstrated objective response rates of up to 56% in HRAS mutant HNSCC. These alternatives are currently under investigation and may offer new treatment options in 2024.

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Tyrosine Kinase Inhibitor

Lenvatinib + Pembrolizumab for Head and Neck Cancer

Phase 2

Waitlist Available

Research Sponsored by Merck Sharp & Dohme Corp.

Eligibility Criteria Checklist

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

Must have

Male participants must refrain from sperm donation, be abstinent from heterosexual intercourse, or use contraception

Hepatitis B surface antigen positive participants must have received antiviral therapy and have undetectable viral load

Must not have

Treated with 4 or more systemic regimens for recurrent/metastatic disease

History of allogeneic tissue/solid organ transplant

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 7 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing if lenvatinib combined with pembrolizumab or lenvatinib alone is better for patients with head and neck cancer that hasn't responded to other treatments. Lenvatinib stops cancer growth, and pembrolizumab boosts the immune system to fight cancer. Lenvatinib has shown better curative effects when combined with other treatments compared to its use as a single agent.

Who is the study for?

This trial is for adults with recurrent/metastatic head and neck squamous cell carcinoma that worsened after platinum therapy and anti-PD-1/PD-L1 treatment. Participants must have measurable disease, be in good physical condition (ECOG 0 or 1), agree to use contraception, and not have other active cancers or severe health conditions.

What is being tested?

The study tests lenvatinib combined with pembrolizumab against standard chemotherapy, and also lenvatinib alone. It aims to see if the combination is more effective based on tumor response rates. Patients are randomly assigned to these treatments.

What are the potential side effects?

Possible side effects include high blood pressure from lenvatinib; immune-related reactions, fatigue, skin issues from pembrolizumab; plus typical chemo side effects like nausea, hair loss, low blood counts leading to infection risk.

Eligibility Criteria

Inclusion Criteria

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

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I am a male and will not donate sperm or will use birth control.

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I have Hepatitis B but am on antiviral therapy with an undetectable viral load.

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My cancer has worsened despite treatments with platinum drugs and PD-1/PD-L1 inhibitors.

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My head or neck cancer has returned or spread and cannot be cured with surgery or radiation.

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I am fully active or can carry out light work.

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My blood pressure is under control.

Exclusion Criteria

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

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I have undergone 4 or more treatments for my recurring or spreading cancer.

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

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My condition can be treated with the aim of curing it.

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I am currently on medication for an infection.

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I have an immune system disorder or recently received treatment that weakens my immune system.

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I have active brain metastases or carcinomatous meningitis.

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I have active tuberculosis.

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I have a severe abnormal connection between my organs.

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I have been diagnosed with HIV.

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I have not had major surgery in the last 3 weeks.

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I have been treated with lenvatinib before.

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My doctor expects I have less than 3 months to live or my disease is getting worse quickly.

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I have trouble swallowing pills.

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I have or had lung inflammation that needed steroids.

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I have a condition that affects how my body absorbs medication taken by mouth.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 7 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 7 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 7 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

Overall Survival (OS)

Secondary study objectives

Duration of Response (DOR)

Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE)

Number of Participants Who Experienced One or More Adverse Events (AEs)

+2 more

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%

Pain in extremity

18%

Abdominal pain upper

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

Influenza

Flatulence

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

Respiratory failure

Monoparesis

Hypercalcaemia

Hepatic failure

Appendicitis

Death

Acute 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

No Placebo-Only Group

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

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Lenvatinib + PembrolizumabExperimental Treatment2 Interventions

Participants will be treated with the combination of lenvatinib (once daily 20 mg oral dose) plus pembrolizumab (200 mg 30-minute intravenous (IV) infusion on Day 1 of each 21-day cycle for 35 cycles), until centrally verified disease progression, or until a protocol-specified discontinuation criterion is met. Participants may receive up to an additional 17 cycles of pembrolizumab as Second Course treatment, with or without lenvatinib.

Group II: Lenvatinib MonotherapyActive Control1 Intervention

Participants will be treated with lenvatinib monotherapy (once daily 24 mg oral dose) until centrally verified disease progression, or until a protocol-specified discontinuation criterion is met.

Group III: SOC ChemotherapyActive Control4 Interventions

Participants will be treated with investigator's choice of standard of care (SOC) chemotherapy (docetaxel, paclitaxel, cetuximab, or capecitabine) until centrally verified disease progression, or until a protocol-specified discontinuation criterion is met.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

2017

Completed Phase 3

~2810

Lenvatinib

2017

Completed Phase 4

~2040

0 / 21Eligibility 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 Oral Squamous Cell Carcinoma (OSCC) include targeted therapies and immunotherapies. Lenvatinib, a multi-kinase inhibitor, targets receptors such as VEGFR, FGFR, PDGFR, RET, and KIT, which are involved in tumor growth and angiogenesis. Pembrolizumab, an anti-PD-1 monoclonal antibody, enhances the immune system's ability to detect and fight tumor cells by blocking the PD-1 pathway, which tumors use to evade immune detection. These mechanisms are important for OSCC patients as they can inhibit tumor growth and improve immune response, potentially leading to better clinical outcomes.

Combination of pembrolizumab and lenvatinib is a potential treatment option for heavily pretreated recurrent and metastatic head and neck cancer.