What is the mechanism of action of this treatment?

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) include targeted therapies and immunotherapies. Targeted therapies focus on specific genetic mutations or biomarkers in cancer cells, such as EGFR mutations or ALK rearrangements, to inhibit their growth and spread while sparing normal cells. Immunotherapies, such as PD-1/PD-L1 inhibitors, boost the immune system's ability to recognize and attack cancer cells by preventing them from evading immune detection. These mechanisms are important for NSCLC patients as they enable personalized treatment approaches, potentially leading to better outcomes and fewer side effects.

What side effects are associated with this type of intervention?

Targeted therapies for NSCLC, such as those inhibiting epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK), can cause side effects including rash, diarrhea, and liver function abnormalities. Immunotherapies, like PD-1/PD-L1 inhibitors (e.g., pembrolizumab, nivolumab) and CTLA-4 inhibitors (e.g., ipilimumab), can lead to immune-related adverse events such as colitis, pneumonitis, hepatitis, endocrinopathies, and skin reactions. These side effects result from the immune system attacking normal tissues in addition to cancer cells.

What prior FDA approvals exist?

The FDA has approved several targeted therapies and immunotherapies for the treatment of Non-Small Cell Lung Cancer (NSCLC). Targeted therapies such as osimertinib, which targets EGFR mutations, and crizotinib, which targets ALK rearrangements, have been approved for specific genetic profiles of NSCLC. Immunotherapies like pembrolizumab and atezolizumab, which are immune checkpoint inhibitors targeting PD-1 and PD-L1 respectively, have also been approved. These drugs work by modulating the immune system to recognize and attack cancer cells. The approval of these therapies has been based on their demonstrated efficacy in improving overall survival and progression-free survival in clinical trials.

What other types of research exist?

Promising novel alternatives to targeted therapies or immunotherapies for NSCLC patients include: 1) Antibody-drug conjugates (ADCs) which deliver cytotoxic agents directly to cancer cells, 2) Tumor Treating Fields (TTFields) which use electric fields to disrupt cancer cell division, and 3) Novel small molecule inhibitors targeting non-traditional pathways involved in cancer growth and survival. These approaches are being actively researched and may offer new avenues for treatment in 2024.

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Other

Multiple Therapies for Stage III Non-Small Cell Lung Cancer

Phase 3

Recruiting

Research Sponsored by Hoffmann-La Roche

Eligibility Criteria Checklist

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

Must have

Documented ALK fusion positivity by an eligible result from: centralized multiplex molecular testing of tumor tissue at the Sponsor's designated central laboratory under Study BX43361 or available results from a Sponsor pre-approved local, appropriately validated ALK fusion test on tumor tissue performed in a Clinical Laboratory Improvement Amendments certified or equivalent laboratory

Histologically or cytologically documented locally advanced, unresectable Stage III NSCLC of either squamous or non-squamous histology

Must not have

Grade >/= 2 peripheral neuropathy

Grade >/= 3 toxicities due to any prior therapy (e.g., RT) (excluding alopecia) that have not shown improvement or are not stable and are considered to interfere with current study drug

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing different treatments to see how well they work and how safe they are. It focuses on patients with advanced lung cancer that cannot be removed by surgery and have specific biological markers. The goal is to find out if these treatments can stop the cancer from growing or spreading and improve patients' health.

Who is the study for?

This trial is for adults with Stage III Non-Small Cell Lung Cancer (NSCLC) who can swallow pills, have had prior chemo and radiotherapy without disease progression, and are expected to live at least 12 weeks. They must not be pregnant or planning pregnancy, agree to use contraception, and have no history of certain bone disorders or severe allergies.

What is being tested?

The study tests the effectiveness and safety of Entrectinib, Durvalumab, Alectinib in NSCLC patients with specific biomarkers. It requires a PET/CT scan for staging and uses electronic patient-reported outcomes for monitoring.

What are the potential side effects?

Potential side effects may include liver issues, digestive disturbances that affect medication absorption, nerve damage symptoms like peripheral neuropathy, immune system reactions leading to inflammation in various organs including lungs (pneumonitis), fatigue from anemia or other blood disorders.

Eligibility Criteria

Inclusion Criteria

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

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My cancer has a confirmed ALK fusion from an approved test.

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My lung cancer is at an advanced stage and cannot be removed by surgery.

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My cancer did not worsen during or after platinum-based chemo.

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My cancer has a ROS1 fusion confirmed by a specific test.

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I can take care of myself and am up and about more than half of my waking hours.

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I have had at least two rounds of platinum-based chemo with or before radiotherapy.

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My radiation therapy was between 54 Gy and 66 Gy, using advanced techniques.

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I can swallow pills whole without breaking them.

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I weigh at least 30 kg.

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My cancer's PD-L1 status is known, tested by a specific method.

Exclusion Criteria

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

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I have moderate to severe numbness, tingling, or pain in my hands or feet.

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I have severe side effects from previous treatments that haven't improved.

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I have a family or personal history of bone disorders.

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I haven't had a severe infection or been hospitalized for one in the last 4 weeks.

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I have no major side effects from previous cancer treatments.

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I am not currently on any cancer treatments like chemotherapy.

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I cannot swallow pills.

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I have a hereditary sugar digestion problem.

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I haven't taken any strong immune system suppressing drugs in the last 2 weeks.

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I have severe liver problems, including issues with liver function or hepatitis.

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My lung cancer has a specific genetic change in the EGFR gene.

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I have been newly diagnosed with Stage III lung cancer that cannot be surgically removed.

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I have had severe lung inflammation from previous radiation therapy.

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I have fully recovered from any past surgeries before starting the study treatment.

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I have a stomach or bowel condition that affects how I absorb pills.

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I haven't had major surgery in the last 4 weeks and don't expect to need one during the study.

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I have been treated with ALK inhibitors before.

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I have previously been treated with specific immune therapies.

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I experience symptoms due to a very slow heartbeat.

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I have had severe side effects from past immunotherapy.

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I have lung conditions that affect my daily activities or need treatment.

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My NSCLC has specific ALK mutations.

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I have a hereditary condition that affects how my body processes certain sugars.

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I have active tuberculosis.

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I have a history of specific lung conditions or signs of lung inflammation on my recent chest scan.

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My cancer has spread to other parts of my body, such as the brain, bones, or lungs.

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I have had a previous transplant of stem cells or an organ.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

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

Nausea

Pyrexia

Vomiting

Dizziness

Acute kidney injury

Musculoskeletal Chest Pain

Pain in extremity

Tinnitus

Jaw fracture

Ankle fracture

Depression

Blood creatine phosphokinase increased

Deep vein thrombosis

Cholelithiasis

Haemoptysis

Syncope

Abscess jaw

Skull fractured base

Paraesthesia

Death

Myocardial infarction

Cerebellar ataxia

Osteoporotic fracture

Invasive ductal breast carcinoma

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

4Treatment groups

Experimental Treatment

Active Control

Group I: Cohort A2: ROS 1-positive (entrectinib arm)Experimental Treatment1 Intervention

Participants will receive entrectinib 600 mg orally once daily until completion of treatment period (3 years), or until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death, whichever occurs first. Cohort A2 has been closed to enrollment.

Group II: Cohort A1: ALK-Positive (alectinib arm)Experimental Treatment1 Intervention

Participants will receive alectinib 600 mg orally twice daily until completion of treatment period (3 years), or until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death, whichever occurs first

Group III: Cohort A2: ROS 1-positive (durvalumab arm)Active Control1 Intervention

Participants will receive 1500 mg of IV durvalumab every 4 weeks until completion of treatment period (1 year) or until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death, whichever occurs first Cohort A2 has been closed to enrollment.

Group IV: Cohort A1: ALK-positive (durvalumab arm)Active Control1 Intervention

Participants will receive 1500 mg of intravenous (IV) durvalumab every 4 weeks until completion of treatment period (1 year) or until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death, whichever occurs first

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Alectinib

2019

Completed Phase 3

~2810

Entrectinib

2014

Completed Phase 2

~360

0 / 37Eligibility 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. Targeted therapies focus on specific genetic mutations or biomarkers in cancer cells, such as EGFR mutations or ALK rearrangements, to inhibit their growth and spread while sparing normal cells. Immunotherapies, such as PD-1/PD-L1 inhibitors, boost the immune system's ability to recognize and attack cancer cells by preventing them from evading immune detection. These mechanisms are important for NSCLC patients as they enable personalized treatment approaches, potentially leading to better outcomes and fewer side effects.

Radiation-induced bystander and abscopal effects: important lessons from preclinical models.Mechanisms of tumor immunotherapy, with a focus on thoracic cancers.