What side effects are associated with this type of intervention?

Common treatments for Adenoid Cystic Carcinoma (ACC) include surgery, radiation therapy, and systemic therapies such as tyrosine kinase inhibitors and immune checkpoint inhibitors. Lenvatinib, a tyrosine kinase inhibitor, is known to cause side effects such as hypertension, fatigue, diarrhea, decreased appetite, and weight loss. Pembrolizumab, a PD-1 inhibitor, can lead to immune-related adverse events including fatigue, rash, pruritus, diarrhea, and more severe conditions like pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

There are no specific FDA approvals for the treatment of Adenoid Cystic Carcinoma (ACC) using Lenvatinib (a tyrosine kinase inhibitor) or Pembrolizumab (a PD-1 inhibitor). However, these drugs are being studied for their efficacy in treating advanced ACC and other salivary gland cancers. Pembrolizumab has been approved for various other cancers, including non-small cell lung cancer and head and neck squamous cell carcinoma, while Lenvatinib is approved for thyroid cancer, renal cell carcinoma, and hepatocellular carcinoma. These approvals suggest potential applicability in ACC treatment, pending further clinical trial results.

What other types of research exist?

Promising novel alternatives to Lenvatinib and Pembrolizumab for Adenoid Cystic Carcinoma patients include: 1) Nivolumab (another PD-1 inhibitor) combined with Ipilimumab (CTLA-4 inhibitor), which has shown efficacy in various cancers. 2) Atezolizumab (PD-L1 inhibitor) combined with chemotherapy, which is being investigated for its effectiveness in different cancer types. 3) Targeted therapies like Osimertinib for patients with specific genetic mutations. These alternatives are based on their potential to provide clinical benefits in similar oncological contexts.

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Tyrosine Kinase Inhibitor

Lenvatinib + Pembrolizumab for Salivary Gland Cancer

Phase 2

Waitlist Available

Led By Alan Ho, MD, PhD

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

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

Must have

Participants must be able to swallow and retain oral medication or have a functioning G-tube in place.

Patients must have RECIST V1.1 measurable disease defined as at least one non-nodal lesion measuring ≥ 20 mm with conventional techniques or as ≥10mm with CT scan, MRI, or calipers by clinical exam in the longest dimension AND/OR a nodal lesion measuring > 15 mm in the shortest dimension. Tumors in previously irradiated fields may be considered measurable if there is evidence of tumor progression after radiation treatment.

Must not have

Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids, or has current pneumonitis/interstitial lung disease.

Active infection (any infection requiring systemic treatment)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing lenvatinib and pembrolizumab in patients with advanced Adenoid Cystic Carcinoma or other salivary gland cancers that have come back or spread. Lenvatinib stops cancer cells from growing, while pembrolizumab helps the immune system attack the cancer. Researchers aim to see if these drugs are effective and safe for these patients. Lenvatinib and pembrolizumab have shown promising results in treating various advanced cancers, including thyroid, liver, endometrial, and gastric cancers.

Who is the study for?

Adults with advanced Adenoid Cystic Carcinoma or other salivary gland cancers that have returned or spread, who've had no recent treatments causing unresolved side effects. They must be able to swallow pills (or have a G-tube), not be pregnant or breastfeeding, and agree to use contraception. Participants need measurable disease and available tumor tissue for study.

What is being tested?

The trial is testing the effectiveness and safety of lenvatinib combined with pembrolizumab in treating advanced salivary gland cancers. It aims to determine if these drugs can help control the cancer when it has recurred or spread elsewhere in the body.

What are the potential side effects?

Potential side effects include high blood pressure, proteinuria (excess protein in urine), heart issues like congestive heart failure or arrhythmias, bleeding events, infections due to immune system suppression, allergic reactions to drug components, pneumonitis/interstitial lung disease.

Eligibility Criteria

Inclusion Criteria

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

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I can swallow pills or have a working G-tube.

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My cancer can be measured by scans and has grown despite previous treatments.

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

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My cancer has returned or spread and cannot be cured with surgery or other treatments.

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I have been diagnosed with adenoid cystic carcinoma.

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I am a male and agree to use contraception and not father children during and up to 120 days after the trial.

Exclusion Criteria

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

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I have or had lung inflammation that needed steroids.

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I do not have any infections requiring treatment through my bloodstream.

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I have not had serious heart issues like heart failure, unstable angina, heart attack, or dangerous arrhythmias in the last 6 months.

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I have had an organ or tissue transplant.

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I have a serious wound, ulcer, or fracture that is not healing and is not caused by cancer.

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I haven't taken any cancer treatment or experimental drugs in the last 4 weeks.

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

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I don't have conditions affecting drug absorption in my gut.

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My urine protein levels are not high.

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I have not used lenvatinib or any PD-1/PD-L1, anti-PD-L2, CTLA-4, OX-40, or CD137 therapies.

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I am on dialysis for kidney failure.

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My high blood pressure is not controlled, even with medication.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 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

best overall response rate

Secondary study objectives

median progression-free survival (PFS)

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%

Abdominal pain upper

18%

Pain in extremity

18%

Dysgeusia

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%

Hypoalbuminaemia

10%

Thrombocytopenia

10%

Oral pain

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

Acute coronary syndrome

Appendicitis

Death

Respiratory failure

Osteoarthritis

Intestinal obstruction

Small intestinal obstruction

Intracranial tumour haemorrhage

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

2Treatment groups

Experimental Treatment

Group I: recurrent/metastatic non-ACC salivary gland cancers (R/M SGC).Experimental Treatment2 Interventions

All eligible patients will undergo informed consent and screening for trial enrollment. Enrolled patients will receive a starting lenvatinib dose of 20mg daily taken orally and pembrolizumab 200mg intravenously every 3 weeks (1 cycle=3 weeks)

Group II: recurrent/metastatic adenoid cystic carcinoma (R/M ACC)Experimental Treatment2 Interventions

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 / 18Eligibility 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, targets multiple receptors involved in tumor growth and angiogenesis, such as VEGFR, FGFR, and PDGFR, thereby reducing tumor vascularization and growth. Pembrolizumab, a PD-1 inhibitor, enhances the immune system's ability to recognize and destroy cancer cells by blocking the PD-1 receptor on T-cells. These mechanisms are crucial for Adenoid Cystic Carcinoma patients as they offer potential control over tumor progression and may improve survival outcomes.

A Phase 2 Trial of Afatinib in Patients with Solid Tumors that Harbor Genomic Aberrations in the HER family: The MOBILITY3 Basket Study.Adenoid Cystic Carcinoma of the Lung with an EGFR Mutation.Salivary Gland Cancers: Biology and Systemic Therapy.