What is the mechanism of action of this treatment?

Pembrolizumab, an immune checkpoint inhibitor, works by targeting the PD-1 receptor on T-cells, thereby preventing cancer cells from evading immune detection and destruction. Lenvatinib, a tyrosine kinase inhibitor, blocks multiple pathways that promote tumor growth and angiogenesis. These mechanisms are significant for ovarian carcinoma patients as they offer a dual approach: enhancing the immune system's ability to target cancer cells and directly inhibiting tumor proliferation and blood supply, potentially leading to better treatment outcomes.

What side effects are associated with this type of intervention?

Common treatments for ovarian carcinoma, particularly those involving immune checkpoint inhibitors like Pembrolizumab and tyrosine kinase inhibitors like Lenvatinib, have several known side effects. Pembrolizumab can cause immune-related adverse events such as skin reactions, endocrine disorders, and pneumonitis. Lenvatinib is associated with hypertension, fatigue, diarrhea, and proteinuria. Combining these treatments may increase the risk of these side effects, necessitating careful monitoring and management by healthcare providers.

What prior FDA approvals exist?

The FDA has approved several treatments for ovarian carcinoma, including immune checkpoint inhibitors and tyrosine kinase inhibitors. Pembrolizumab, an immune checkpoint inhibitor targeting PD-1, has been approved for various cancers, including ovarian carcinoma, particularly in cases with high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR). Lenvatinib, a tyrosine kinase inhibitor, has been studied in combination with pembrolizumab for its efficacy in treating advanced solid tumors, including ovarian carcinoma. These approvals highlight the evolving landscape of targeted therapies in ovarian cancer treatment.

What other types of research exist?

Promising alternatives to Pembrolizumab and Lenvatinib for ovarian carcinoma patients include: 1) Nivolumab (another immune checkpoint inhibitor) which has shown efficacy in various cancers including non-small cell lung cancer and melanoma. 2) Atezolizumab (an anti-PD-L1 therapy) which has been effective in several cancers such as urothelial carcinoma and non-small cell lung cancer. 3) Bevacizumab (an anti-VEGF therapy) which is often used in combination with chemotherapy for ovarian cancer. 4) PARP inhibitors like Olaparib and Niraparib, which are particularly effective in patients with BRCA mutations or homologous recombination deficiency. These alternatives offer different mechanisms of action and may provide additional options for treatment.

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Tyrosine Kinase Inhibitor

Pembrolizumab + Lenvatinib for Ovarian Cancer

Phase 2

Recruiting

Led By Elizabeth K Lee, MD

Research Sponsored by Elizabeth K. Lee MD

Eligibility Criteria Checklist

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

Must have

Age ≥18 years

Participants must have received at least one prior platinum-based chemotherapeutic regimen for primary management of disease

Must not have

Evidence of bowel involvement

Any gastrointestinal disorder that would interfere with the passage or absorption of oral medications

Timeline

Screening 3 weeks

Treatment Varies

Follow Up disease will be evaluated every 3 cycles on treatment (each cycle is 3 weeks); treatment continues until disease progression or unacceptable toxicity. treatment duration is expected to be up to 3 years.

Awards & highlights

No Placebo-Only Group

Summary

This trial tests the combination of pembrolizumab and lenvatinib in patients with clear cell ovarian cancer that has returned or not responded to treatment. Pembrolizumab boosts the immune system to fight cancer, and lenvatinib blocks proteins that help cancer grow. These medications have been used together for various cancers, showing promising results.

Who is the study for?

This trial is for adults over 18 with recurrent or persistent clear cell ovarian cancer who've had at least one platinum-based chemotherapy. They must have measurable disease, stable health status (ECOG 0 or 1), adequate organ function, controlled blood pressure, and no major recent surgeries. Women of childbearing age need a negative pregnancy test and agree to use contraception.

What is being tested?

The study tests the combination of pembrolizumab and lenvatinib in treating clear cell ovarian cancer. It aims to determine how safe and effective this drug duo is when given together to patients who meet specific health criteria.

What are the potential side effects?

Potential side effects may include high blood pressure, fatigue, loss of appetite, thyroid dysfunction, nausea, mouth sores, rash or redness on hands/feet. More serious risks involve immune system reactions that could affect lungs or intestines.

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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I have had platinum-based chemotherapy for my disease.

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My ovarian cancer is mainly clear cell type.

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I have at least one cancer lesion that can be measured.

Select...

I am fully active or able to carry out light work.

Exclusion Criteria

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

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My cancer has spread to my intestines.

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I do not have stomach or bowel problems affecting medication absorption.

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My urine protein is less than 1g/24 hours.

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I have not had serious bleeding in the last 4 weeks.

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I have previously taken lenvatinib.

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I have not had radiation therapy in the last 2 weeks.

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I haven't had any cancer treatment in the last 4 weeks.

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

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I have been diagnosed with an immune system disorder.

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I am allergic to lenvatinib, pembrolizumab, or similar drugs.

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I have a serious heart condition.

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I have not had major surgery in the last 4 weeks.

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I have tested positive for Hepatitis B or C.

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I have or had lung inflammation that needed steroids.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ disease will be evaluated every 3 cycles on treatment (each cycle is 3 weeks); treatment continues until disease progression or unacceptable toxicity. treatment duration is expected to be up to 3 years.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~disease will be evaluated every 3 cycles on treatment (each cycle is 3 weeks); treatment continues until disease progression or unacceptable toxicity. treatment duration is expected to be up to 3 years.

This trial's timeline: 3 weeks for screening, Varies for treatment, and disease will be evaluated every 3 cycles on treatment (each cycle is 3 weeks); treatment continues until disease progression or unacceptable toxicity. treatment duration is expected to be up to 3 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

6 Month Progression-free survival (PFS) Rate

Overall Response Rate (ORR)

Secondary study objectives

Clinical Benefit Rate (CBR)

Grade 3 or Higher Treatment-Related Toxicity Rate

Median Overall Survival (OS)

+7 more

Side effects data

From 2024 Phase 3 trial • 804 Patients • NCT03040999

64%

Radiation skin injury

63%

Stomatitis

58%

Anaemia

56%

Nausea

48%

Dry mouth

45%

Constipation

45%

Weight decreased

44%

Dysphagia

42%

Neutrophil count decreased

33%

Dysgeusia

33%

Vomiting

32%

Fatigue

31%

White blood cell count decreased

28%

Hypomagnesaemia

26%

Decreased appetite

25%

Hypothyroidism

25%

Hypokalaemia

24%

Lymphocyte count decreased

24%

Platelet count decreased

23%

Oropharyngeal pain

23%

Blood creatinine increased

22%

Diarrhoea

22%

Odynophagia

20%

Hypoacusis

20%

Alanine aminotransferase increased

20%

Hyponatraemia

19%

Tinnitus

19%

Oral candidiasis

19%

Asthenia

16%

Pyrexia

16%

Cough

15%

Aspartate aminotransferase increased

15%

Rash

14%

Insomnia

13%

Acute kidney injury

13%

Pharyngeal inflammation

13%

Pruritus

12%

Dysphonia

12%

Gamma-glutamyltransferase increased

11%

Pneumonia

11%

Dehydration

10%

Hyperthyroidism

10%

Hypoalbuminaemia

10%

Hypocalcaemia

10%

Headache

10%

Productive cough

Neck pain

Peripheral sensory neuropathy

Gastrooesophageal reflux disease

Hiccups

Hyperglycaemia

Hyperuricaemia

Dizziness

Hypophosphataemia

Urinary tract infection

Ear pain

Localised oedema

Hyperkalaemia

Erythema

Oral pain

Abdominal pain upper

Arthralgia

Anxiety

Febrile neutropenia

Dyspepsia

Saliva altered

Back pain

Oedema peripheral

Hypertension

Dyspnoea

Nasopharyngitis

Alopecia

Dry skin

Sepsis

Pneumonia aspiration

Trismus

Pneumonitis

Laryngeal oedema

Malnutrition

Pharyngeal haemorrhage

Cellulitis

Septic shock

Systemic infection

Clostridium difficile colitis

Cardiac arrest

Death

Bronchitis

Hepatitis

Immune-mediated hepatitis

Oesophagitis

General physical health deterioration

Hypophagia

Tumour haemorrhage

Cerebrovascular accident

Syncope

Acute respiratory failure

Aspiration

Colitis

Mouth haemorrhage

Hypersensitivity

Acute myocardial infarction

Abscess neck

Device related infection

Stoma site infection

Vascular device infection

Wound infection

Hypercalcaemia

Pulmonary embolism

Respiratory failure

100%

80%

60%

40%

20%

Study treatment Arm

Pembrolizumab + CRT Followed by Pembrolizumab

Placebo + CRT Followed by Placebo

Awards & Highlights

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 and LENVATINIBExperimental Treatment2 Interventions

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. The names of the study drugs involved in this study are: * Lenvatinib * Pembrolizumab Treatment will continue until progression of disease or unacceptable toxicity. Participants will be followed for up to 36 months after discontinuation of study treatment.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Lenvatinib

2017

Completed Phase 4

~2070

Pembrolizumab

2017

Completed Phase 3

~3150

0 / 19Eligibility 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

Pembrolizumab, an immune checkpoint inhibitor, works by targeting the PD-1 receptor on T-cells, thereby preventing cancer cells from evading immune detection and destruction. Lenvatinib, a tyrosine kinase inhibitor, blocks multiple pathways that promote tumor growth and angiogenesis. These mechanisms are significant for ovarian carcinoma patients as they offer a dual approach: enhancing the immune system's ability to target cancer cells and directly inhibiting tumor proliferation and blood supply, potentially leading to better treatment outcomes.