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PD-1 Inhibitor

Lenvatinib + Pembrolizumab for Colorectal Cancer

Phase 3

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

Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 3 days prior to randomization

Has measurable disease per RECIST 1.1 assessed by the investigator Has provided to a designated central laboratory an archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion which has not been previously irradiated

Must not have

Has a history of arterial thromboembolism within 12 months of start of study drug

Has preexisting ≥Grade 3 gastrointestinal or nongastrointestinal fistula

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 22 months

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing whether a new combination therapy of lenvatinib and pembrolizumab is better than the standard of care for metastatic colorectal cancer in terms of overall survival.

Who is the study for?

This trial is for adults with metastatic colorectal cancer that's not microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR). They must have tried standard treatments without success and be able to swallow pills. Participants need a life expectancy of at least 3 months, stable blood pressure, and an ECOG performance status of 0-1. Women must use effective contraception or not be of childbearing potential; men also agree to contraception.

What is being tested?

The study tests if lenvatinib combined with pembrolizumab improves survival in metastatic colorectal cancer compared to the standard care drugs regorafenib and TAS-102. It aims to prove this combination leads to longer lives for patients who've already tried other treatments.

What are the potential side effects?

Possible side effects include high blood pressure, fatigue, diarrhea, decreased appetite, weight loss, joint/muscle pain, hypertension, proteinuria (high levels of protein in urine), thyroid dysfunction and palmar-plantar erythrodysesthesia syndrome ('hand-foot' syndrome).

Eligibility Criteria

Inclusion Criteria

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

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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 can be measured and I can provide a tissue sample that hasn't been treated with radiation.

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I have provided a sample of my tumor that hasn't been treated with radiation to a lab.

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My colorectal cancer is advanced and cannot be surgically removed, and it is not MSI-H/dMMR.

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I can take medicine in pill form or through a feeding tube.

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My cancer progressed after standard treatments, including specific drugs if they were available and suitable for my cancer type.

Exclusion Criteria

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

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I had a blood clot in an artery in the last year.

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I have a severe fistula.

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I have fluid buildup needing drainage or medication in the last 2 weeks.

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My tumor is identified as MSI-H/dMMR.

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I am currently being treated for an infection.

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I have had pneumonitis treated with steroids or have it now.

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My heart's pumping ability is below normal.

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I've been treated with specific immune and blood vessel growth inhibitors.

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I have been diagnosed with HIV.

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My scans show cancer affecting major blood vessels in my chest.

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I have a history of Hepatitis B or active Hepatitis C.

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I have not had a live vaccine in the last 30 days.

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

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I haven't had serious heart problems in the last year.

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I do not have severe heart failure.

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I have taken regorafenib or TAS-102 before.

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I have a gut condition that could affect how I absorb medication.

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My cancer has spread to my brain or spinal cord.

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I have been treated for an autoimmune disease in the last 2 years.

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I have a serious wound, ulcer, or bone fracture that is not healing.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 22 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 22 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 22 months 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

Change From Baseline in EORTC QLQ-C30 Appetite Loss (Item 13) Score

Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score

Change From Baseline in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score

+10 more

Side effects data

From 2024 Phase 3 trial • 794 Patients • NCT03713593

47%

Diarrhoea

45%

Hypertension

42%

Hypothyroidism

37%

Decreased appetite

34%

Palmar-plantar erythrodysaesthesia syndrome

33%

Proteinuria

32%

Fatigue

30%

Weight decreased

29%

Aspartate aminotransferase increased

26%

Blood bilirubin increased

25%

Platelet count decreased

23%

Alanine aminotransferase increased

23%

Nausea

22%

Arthralgia

21%

Dysphonia

18%

Abdominal pain

18%

Asthenia

17%

Pruritus

17%

Constipation

16%

Gamma-glutamyltransferase increased

16%

Rash

16%

Oedema peripheral

15%

Hypoalbuminaemia

14%

Lipase increased

14%

Back pain

13%

Cough

13%

Vomiting

12%

Headache

12%

Blood alkaline phosphatase increased

12%

Anaemia

11%

Abdominal pain upper

11%

Pyrexia

11%

Hyponatraemia

11%

Dyspnoea

10%

Amylase increased

10%

Blood creatinine increased

10%

Stomatitis

Hypokalaemia

Insomnia

Neutrophil count decreased

Urinary tract infection

Hyperthyroidism

Dyspepsia

Abdominal distension

White blood cell count decreased

Haematuria

Ascites

Hypertriglyceridaemia

Myalgia

Dizziness

Toothache

Mucosal inflammation

Hyperglycaemia

Hypomagnesaemia

Epistaxis

Hypophosphataemia

Pain in extremity

Dysgeusia

Oropharyngeal pain

Hepatic encephalopathy

Neutropenia

Dry mouth

Malaise

Hyperkalaemia

Pneumonia

General physical health deterioration

Hepatic pain

Pancreatitis

Pneumonia klebsiella

Septic shock

Hepatic failure

Tumour haemorrhage

Angina pectoris

Myocardial infarction

Gastric ulcer haemorrhage

Gastrointestinal haemorrhage

Hepatorenal syndrome

COVID-19

COVID-19 pneumonia

Atrial fibrillation

Immune thrombocytopenia

Acute myocardial infarction

Adrenal insufficiency

Hypophysitis

Colitis

Gastric haemorrhage

Haemorrhoidal haemorrhage

Death

Multiple organ dysfunction syndrome

Immune-mediated hepatitis

Sepsis

Dehydration

Diabetic ketoacidosis

Hypoglycaemia

Tumour lysis syndrome

Cerebrovascular accident

Depressed level of consciousness

Ischaemic stroke

Seizure

Acute kidney injury

Pemphigoid

100%

80%

60%

40%

20%

Study treatment Arm

Lenvatinib + Placebo

Lenvatinib + Pembrolizumab

Awards & Highlights

No Placebo-Only Group

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

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: lenvatinib+pembrolizumabExperimental Treatment2 Interventions

Participants receive pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.

Group II: standard of care treatment (regorafenib OR TAS-102)Active Control2 Interventions

Participants receive regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m\^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

lenvatinib

2018

Completed Phase 3

~1950

pembrolizumab

2017

Completed Phase 3

~6070