What side effects are associated with this type of intervention?

Alectinib, an ALK inhibitor used in the treatment of ALK-positive NSCLC, commonly causes side effects such as fatigue, constipation, edema, myalgia, and increased liver enzymes. Crizotinib, another ALK inhibitor, shares similar side effects but also frequently causes visual disturbances, nausea, diarrhea, and vomiting. Other common treatments for NSCLC, such as chemotherapy, can lead to side effects like hair loss, anemia, infection risk, and gastrointestinal issues. Immunotherapy, including agents like pembrolizumab and atezolizumab, may cause immune-related adverse effects such as rash, colitis, pneumonitis, and endocrinopathies.

What prior FDA approvals exist?

Alectinib is an ALK inhibitor used in the treatment of ALK-positive NSCLC. Other FDA-approved ALK inhibitors for NSCLC include Crizotinib, Ceritinib, Brigatinib, and Lorlatinib. These drugs target the anaplastic lymphoma kinase (ALK) gene rearrangements found in a subset of NSCLC patients, offering a targeted therapy option that has shown efficacy in improving progression-free survival and overall response rates compared to traditional chemotherapy.

What other types of research exist?

Promising novel alternatives to Alectinib for ALK-positive NSCLC patients include Lorlatinib, which has shown efficacy in patients who have progressed on other ALK inhibitors, and Brigatinib, which has demonstrated effectiveness in both treatment-naive and previously treated patients. Additionally, Ensartinib is another ALK inhibitor that has shown promising results in clinical trials. These alternatives offer new options for patients considering treatment in 2024.

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Tyrosine Kinase Inhibitor

Alectinib vs Crizotinib for Non-Small Cell Lung Cancer (ALEX Trial)

Phase 3

Waitlist Available

Research Sponsored by Hoffmann-La Roche

Eligibility Criteria Checklist

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

Must have

Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is ALK-positive as assessed by the Ventana immunohistochemistry (IHC) test

Eastern cooperative oncology group performance status (ECOG PS) of 0-2

Must not have

Any gastrointestinal (GI) disorder or liver disease

Participants with baseline QTc greater than (>) 470 milliseconds or symptomatic bradycardia

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline up to 28 months in the crizotinib arm and up to 30 months in the alectinib arm

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial compares two medications, alectinib and crizotinib, for treating a specific type of advanced lung cancer. The patients have not received any prior treatment for their cancer. Both drugs work by blocking a protein that helps the cancer cells grow. Alectinib has shown superior effectiveness and fewer side effects compared to crizotinib in treating this type of lung cancer.

Who is the study for?

This trial is for adults with advanced non-small cell lung cancer that tests positive for ALK, who haven't had treatment before. They should be generally healthy, not pregnant or breastfeeding, and willing to use effective contraception. People can't join if they've taken certain drugs recently, have serious health issues affecting the study or drug absorption, a history of severe allergies to trial drugs' ingredients, or other cancers within 3 years.

What is being tested?

The study compares two oral medications: Alectinib (600 mg twice daily) versus Crizotinib (250 mg twice daily), in people with untreated ALK-positive advanced NSCLC. Participants are randomly assigned to one of these treatments until their disease worsens or they experience unacceptable side effects.

What are the potential side effects?

Possible side effects include liver problems, digestive issues like nausea and diarrhea, vision disorders due to swelling in the retina for Alectinib users; heart rhythm changes especially QT prolongation for Crizotinib users; fatigue and potential allergic reactions.

Eligibility Criteria

Inclusion Criteria

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

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My lung cancer is advanced or has returned, and tests show it's ALK-positive.

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I am able to get out of my bed or chair and move around.

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I have advanced lung cancer and haven't received any systemic treatment for it.

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I am not pregnant.

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My cancer can be measured using specific criteria before starting the study treatment.

Exclusion Criteria

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

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I have a stomach or liver condition.

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My heart's electrical activity (QTc) is over 470 milliseconds, or I have slow heartbeat symptoms.

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I am allergic to ingredients in alectinib or crizotinib.

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I have experienced severe side effects from previous cancer treatments, except for hair loss.

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I haven't taken strong drugs that affect liver enzymes in the last 14 days.

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I have had cancer within the last 3 years.

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I have had an organ transplant.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline up to 28 months in the crizotinib arm and up to 30 months in the alectinib arm

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline up to 28 months in the crizotinib arm and up to 30 months in the alectinib arm

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline up to 28 months in the crizotinib arm and up to 30 months in the alectinib arm for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Percentage of Participants With PFS Event by Investigator Assessment

Progression-Free Survival (PFS) by Investigator Assessment

Secondary study objectives

CNS DOR IRC-assessed According to RECIST v1.1 Criteria

Duration of Response (DOR) According to RECIST V1.1 Criteria as Assessed by the Investigators

HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing

+17 more

Side effects data

From 2018 Phase 3 trial • 119 Patients • NCT02604342

21%

Constipation

16%

Anaemia

14%

Oedema peripheral

14%

Myalgia

13%

Back pain

12%

Asthenia

12%

Dyspnoea

10%

Cough

Decreased appetite

Upper Respiratory Tract Infection

Blood bilirubin increased

Pneumonia

Diarrhoea

Fatigue

Headache

Abdominal Pain

Blood Creatinine Increased

Bronchitis

Arthralgia

Electrocardiogram QT Prolonged

Nasopharyngitis

Pyrexia

Vomiting

Nausea

Dizziness

Acute kidney injury

Musculoskeletal Chest Pain

Pain in extremity

Tinnitus

Invasive ductal breast carcinoma

Depression

Deep vein thrombosis

Haemoptysis

Paraesthesia

Cholelithiasis

Myocardial infarction

Abscess jaw

Jaw fracture

Blood creatine phosphokinase increased

Ankle fracture

Skull fractured base

Cerebellar ataxia

Syncope

Osteoporotic fracture

Death

Diverticulitis

Erysipelas

H1N1 Influenza

Pharyngitis

Wound Complication

Neuropathy peripheral

Alopecia

Epilepsy

Abdominal pain

Hypertension

100%

80%

60%

40%

20%

Study treatment Arm

Experimental: Alectinib

Active Comparator: Premetrexed/Docetaxel

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: AlectinibExperimental Treatment1 Intervention

Participants will receive alectinib from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.

Group II: CrizotinibActive Control1 Intervention

Participants will receive crizotinib from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Alectinib

2019

Completed Phase 3

~2810

0 / 12Eligibility 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 Non-Small Cell Lung Cancer (NSCLC) include targeted therapies and immunotherapies. ALK inhibitors, such as alectinib, work by blocking the activity of the anaplastic lymphoma kinase (ALK) protein, which is involved in the growth and spread of cancer cells in ALK-positive NSCLC. This targeted approach helps to specifically inhibit cancer cell proliferation while sparing normal cells, leading to fewer side effects compared to traditional chemotherapy. Similarly, EGFR inhibitors target mutations in the epidermal growth factor receptor (EGFR) gene, which are common in certain NSCLC subtypes, thereby preventing cancer cell growth and survival. Immunotherapies, such as PD-1/PD-L1 inhibitors, enhance the body's immune response against cancer cells. These treatments are significant for NSCLC patients as they offer more personalized and effective options, often leading to better outcomes and improved quality of life.

A case of ALK-rearranged non-small cell lung cancer that responded to ceritinib after development of resistance to alectinib.Activation of EGFR Bypass Signaling by TGFα Overexpression Induces Acquired Resistance to Alectinib in ALK-Translocated Lung Cancer Cells.