What is the mechanism of action of this treatment?

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) with ROS1 rearrangements include targeted therapies like Repotrectinib and Crizotinib. These drugs function as tyrosine kinase inhibitors (TKIs) that specifically target the ROS1 fusion protein, which is involved in the growth and proliferation of cancer cells. By inhibiting the ROS1 kinase activity, these treatments effectively block the signaling pathways that drive tumor growth. This targeted approach is crucial for NSCLC patients as it offers a more personalized treatment option, potentially leading to better outcomes and fewer side effects compared to conventional chemotherapy.

What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) that involve ROS1 inhibition, such as Repotrectinib and Crizotinib, often have side effects including nausea, vomiting, diarrhea, constipation, and fatigue. Patients may also experience liver enzyme abnormalities, visual disturbances, dizziness, and edema. More severe but less common side effects can include interstitial lung disease, QT prolongation, and hepatotoxicity. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of ROS1-positive Non-Small Cell Lung Cancer (NSCLC). Crizotinib was one of the first ROS1 inhibitors approved for this indication, demonstrating significant efficacy in patients with ROS1 rearrangements. Lorlatinib is another FDA-approved drug for ROS1-positive NSCLC, particularly for patients who have progressed on or are intolerant to Crizotinib. These drugs target the ROS1 gene rearrangement, which is a driver mutation in a subset of NSCLC patients.

What other types of research exist?

Brigatinib is a promising alternative for ROS1-positive NSCLC, especially in cases resistant to Crizotinib. Other potential treatments include immunotherapy combinations such as pembrolizumab plus chemotherapy or atezolizumab plus bevacizumab and chemotherapy, which have shown efficacy in NSCLC.

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Tyrosine Kinase Inhibitor

Repotrectinib vs Crizotinib for Non-Small Cell Lung Cancer

Phase 3

Recruiting

Research Sponsored by Bristol-Myers Squibb

Eligibility Criteria Checklist

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

Must have

Up to 1 prior line of systemic treatment for NSCLC is permitted

ECOG Performance Status ≤ 2

Must not have

Known tumor targetable co-mutations or rearrangements

Clinically significant cardiovascular disease (either active or within 6 months prior to enrollment)

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 two medications, repotrectinib and crizotinib, in patients with a specific type of lung cancer that hasn't been treated with certain drugs before. These medications work by blocking a protein that helps cancer cells grow and spread. The goal is to see if these treatments are effective and safe for these patients.

Who is the study for?

This trial is for adults with advanced or metastatic non-small cell lung cancer (NSCLC) that haven't been treated with TKIs but may have had one other treatment. They need to have a specific gene change called ROS1 and be in good enough health to do their daily activities (ECOG ≤ 2). People can't join if they've got certain brain issues, heart disease, other cancers treated within the last 2 years, or specific genetic changes.

What is being tested?

The study compares Repotrectinib and Crizotinib's effectiveness and safety in treating NSCLC patients who are new to TKI treatments. Participants will receive either drug to see which works better at controlling lung cancer growth.

What are the potential side effects?

Possible side effects of both Repotrectinib and Crizotinib include liver problems, vision issues, nausea, diarrhea, edema (swelling), heart issues like slow heartbeat or QT prolongation on an EKG. Each person might react differently.

Eligibility Criteria

Inclusion Criteria

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

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I have had only one treatment for my lung cancer.

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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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My lung cancer is advanced or has spread to other areas.

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My cancer has a ROS1 gene change.

Select...

I have not taken any TKI medications for ROS1-positive lung cancer.

Exclusion Criteria

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

Select...

My tumor has specific genetic changes that can be targeted by treatment.

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I have not had serious heart problems in the last 6 months.

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I have symptoms from cancer spread to my brain or its coverings.

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 2020 Phase 3 trial • 207 Patients • NCT01639001

66%

Alanine aminotransferase increased

61%

Diarrhoea

60%

Aspartate aminotransferase increased

59%

Vomiting

54%

Nausea

41%

White blood cell count decreased

40%

Visual impairment

38%

Neutrophil count decreased

36%

Constipation

32%

Cough

28%

Headache

27%

Dizziness

26%

Oedema peripheral

26%

Decreased appetite

25%

Blood albumin decreased

21%

Pain in extremity

21%

Nasopharyngitis

20%

Neutropenia

19%

Anaemia

18%

Pyrexia

18%

Hypoalbuminaemia

17%

Upper respiratory tract infection

15%

Chest pain

15%

Dyspnoea

14%

Disease progression

14%

Blood lactate dehydrogenase increased

13%

Blood creatine phosphokinase increased

13%

Sinus bradycardia

13%

Vision blurred

13%

Gamma-glutamyltransferase increased

13%

Back pain

13%

Insomnia

13%

Protein total decreased

13%

Hypocalcaemia

12%

Rash

12%

Leukopenia

12%

Hypokalaemia

11%

Abdominal distension

10%

Abdominal pain

10%

Blood alkaline phosphatase increased

10%

Pain

10%

Alopecia

Chest discomfort

Blood creatinine increased

Fatigue

Oedema

Hypoaesthesia

Asthenia

Lymphocyte count decreased

Arthralgia

Abdominal pain upper

Platelet count decreased

Hypertension

Haemoptysis

Face oedema

Photopsia

Toothache

Haemoglobin decreased

Paraesthesia

Muscular weakness

Taste disorder

Bradycardia

Pneumonia

Blood creatine phosphokinase MB increased

Hyponatraemia

Hypoproteinaemia

Musculoskeletal pain

Red blood cell count decreased

Productive cough

Blood bilirubin increased

Pruritus

Thrombocytopenia

Pulmonary embolism

Dysphagia

Interstitial lung disease

Death

Pleural effusion

Pneumothorax

Subcutaneous emphysema

Hepatic function abnormal

Abdominal discomfort

Intestinal obstruction

Pancreatitis

Pancreatitis acute

Anaphylactic shock

Impaired healing

Phlebitis

Drug-induced liver injury

Gastrointestinal viral infection

Lower respiratory tract infection

Goitre

Ocular hypertension

Post procedural infection

Deep vein thrombosis

Cellulitis

Hyperuricaemia

Colon adenoma

Adenomyosis

Circulatory collapse

Fracture

Altered state of consciousness

100%

80%

60%

40%

20%

Study treatment Arm

Crizotinib

Chemotherapy

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: Arm AExperimental Treatment1 Intervention

Group II: Arm BActive Control1 Intervention

0 / 8Eligibility 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) with ROS1 rearrangements include targeted therapies like Repotrectinib and Crizotinib. These drugs function as tyrosine kinase inhibitors (TKIs) that specifically target the ROS1 fusion protein, which is involved in the growth and proliferation of cancer cells. By inhibiting the ROS1 kinase activity, these treatments effectively block the signaling pathways that drive tumor growth. This targeted approach is crucial for NSCLC patients as it offers a more personalized treatment option, potentially leading to better outcomes and fewer side effects compared to conventional chemotherapy.

Comparative effectiveness analysis between entrectinib clinical trial and crizotinib real-world data in ROS1+ NSCLC.Safety and Efficacy of Crizotinib in Patients With Advanced or Metastatic ROS1-Rearranged Lung Cancer (EUCROSS): A European Phase II Clinical Trial.Emerging therapeutic agents for lung cancer.