Repotrectinib vs Crizotinib for Non-Small Cell Lung Cancer

Recruiting at 261 trial locations

Overseen By BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bristol-Myers Squibb

Must not be taking: TKIs

Disqualifiers: Brain metastases, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

190 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Crizotinib for non-small cell lung cancer?

Crizotinib has shown significant anticancer activity in patients with advanced non-small-cell lung cancer (NSCLC) that have specific genetic changes, such as ALK or ROS1 rearrangements. Studies have demonstrated that Crizotinib can induce remissions and extend the lives of patients with these genetic profiles. ^{1 2 3 4 5}

What is known about the safety of Crizotinib and Repotrectinib in humans?

Crizotinib, also known as Xalkori, has been generally well tolerated in patients with non-small cell lung cancer, but it can cause side effects like vision problems, nausea, diarrhea, and in some cases, severe lung disease. No new safety concerns have been reported in recent studies, and its safety profile is consistent with previous findings. ^{6 7 8 9 10}

How does the drug Repotrectinib differ from Crizotinib for treating non-small cell lung cancer?

Repotrectinib is a newer drug designed to overcome resistance that often develops with Crizotinib, which is an older treatment for non-small cell lung cancer targeting specific genetic changes (ALK and ROS1 rearrangements). Repotrectinib is considered more potent and structurally different, potentially offering better outcomes for patients who no longer respond to Crizotinib. ^{3 9 11 12 13}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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.

Inclusion Criteria

You have at least one visible and measurable abnormality that the doctor can see and measure.

I have had only one treatment for my lung cancer.

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

Exclusion Criteria

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

I haven't had cancer treatment in the past 2 years, except for skin cancer or fully removed in situ carcinoma.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either repotrectinib or crizotinib to evaluate efficacy and safety

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Crizotinib
• Repotrectinib

Trial Overview 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.

Participant Groups

Group I: Arm A Experimental Treatment 1 Intervention

Group II: Arm B Active Control 1 Intervention

Crizotinib is already approved in United States, European Union, Japan, Canada for the following indications:

Approved in United States as Xalkori for:

• Non-small cell lung cancer (NSCLC) with ALK rearrangements

Approved in European Union as Xalkori for:

• Non-small cell lung cancer (NSCLC) with ALK rearrangements

Approved in Japan as Xalkori for:

• Non-small cell lung cancer (NSCLC) with ALK rearrangements

Approved in Canada as Xalkori for:

• Non-small cell lung cancer (NSCLC) with ALK rearrangements

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Zai Lab (Shanghai) Co., Ltd.

Industry Sponsor

Trials

30

Recruited

3,800+

Findings from Research

Crizotinib is a targeted therapy that has shown significant anticancer activity in patients with advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer, leading to its FDA approval in 2011.

This review highlights crizotinib's efficacy as a personalized treatment option compared to traditional chemotherapy for patients who have already undergone treatment for non-small-cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizotinib as a personalized alternative for targeted anaplastic lymphoma kinase rearrangement in previously treated patients with non-small-cell lung cancer. Guo, L., Zhang, H., Shao, W., et al.[2018]

Crizotinib is an effective treatment for patients with ALK-positive non-small-cell lung cancer (NSCLC), showing significant clinical benefits and leading to its early approval by the USFDA in 2011.

Despite its effectiveness in inducing remissions and prolonging patient survival, there are concerns about emerging resistance to crizotinib therapy, highlighting the need for ongoing research and development of new treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizotinib: A comprehensive review. Sahu, A., Prabhash, K., Noronha, V., et al.[2022]

In a study of 35 Chinese patients with advanced non-small-cell lung cancer (NSCLC) harboring ROS1 rearrangements, crizotinib demonstrated a high objective response rate of 71.4% and a disease control rate of 94.3%, indicating its efficacy in real-world clinical practice.

The median progression-free survival was 11 months and median overall survival was 41 months, with crizotinib being well tolerated despite some common adverse effects like elevated transaminases and vision disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizotinib in Chinese Patients with ROS1-Rearranged Advanced Non‒Small-Cell Lung Cancer in Routine Clinical Practice. Liu, C., Yu, H., Chang, J., et al.[2022]

Crizotinib, an oral ALK inhibitor approved in 2011, significantly improves response rates and progression-free survival in patients with metastatic ALK mutation-driven non-small-cell lung cancer (NSCLC) compared to standard chemotherapy.

Ceritinib, approved in 2014 for patients who are intolerant to or have developed resistance to crizotinib, showed a 56% overall response rate and a median progression-free survival of seven months in a clinical trial of 130 patients with ALK-positive NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of anaplastic lymphoma kinase inhibition in the treatment of non-small-cell lung cancer. Croegaert, K., Kolesar, JM.[2022]

Crizotinib is an effective oral tyrosine kinase inhibitor specifically targeting the EML4-ALK fusion oncogene found in about 5% of non-small-cell lung cancer (NSCLC) cases, demonstrating its efficacy in treating this specific subset of lung cancer.

In addition to its primary use for ALK-positive NSCLC, crizotinib shows potential activity against other lung cancer types with MET oncogene mutations or ROS1 translocations, indicating its broader therapeutic applicability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizotinib in the treatment of non-small-cell lung cancer. Forde, PM., Rudin, CM.[2018]

Crizotinib is an effective treatment for adults with ALK-rearranged non-small-cell lung cancer, but managing its common side effects is essential for maintaining treatment continuity and achieving optimal survival rates.

While some side effects like visual disturbances and bradycardia are generally mild, serious cardiac and liver-related adverse events require careful monitoring, particularly for QT interval prolongation and liver function, to ensure patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ALK-rearranged non-small cell lung cancers: how best to optimize the safety of crizotinib in clinical practice? Girard, N., Audigier-Valette, C., Cortot, AB., et al.[2018]

In a phase II trial involving 127 East Asian patients with ROS1-positive advanced non-small-cell lung cancer (NSCLC), crizotinib showed a high objective response rate of 71.7%, indicating significant antitumor activity.

The treatment was well tolerated, with no new safety concerns reported, and patients experienced durable responses, with a median duration of response of 19.7 months and a median progression-free survival of 15.9 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Crizotinib in East Asian Patients With ROS1-Positive Advanced Non-Small-Cell Lung Cancer. Wu, YL., Yang, JC., Kim, DW., et al.[2022]

Crizotinib (XALKORI) is an effective treatment for patients with ALK-positive non-small cell lung cancer (NSCLC), showing an objective response rate of 61% in one trial and 50% in another, with median response durations of 48 and 42 weeks, respectively.

The drug was granted accelerated approval due to its high response rates and durability, and later received full approval after demonstrating improved progression-free survival in patients previously treated with platinum-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration approval: crizotinib for treatment of advanced or metastatic non-small cell lung cancer that is anaplastic lymphoma kinase positive. Malik, SM., Maher, VE., Bijwaard, KE., et al.[2022]

Crizotinib is an effective oral tyrosine kinase inhibitor specifically targeting ALK, which is found in about 5% of non-small-cell lung cancers (NSCLCs), and has been approved for treating advanced ALK-rearranged NSCLC.

Clinical trials have demonstrated that crizotinib is superior to standard chemotherapy for patients with ALK-positive NSCLC, highlighting its efficacy in this specific cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizotinib in the treatment of non--small-cell lung cancer. Rothschild, SI., Gautschi, O.[2021]

In a study of 29 patients treated with crizotinib, 6 cases of interstitial lung disease (ILD) were identified, highlighting a significant risk of severe lung complications associated with this medication.

The less severe form of ILD, which developed gradually and was associated with better progression-free survival (19.9 months), suggests that while crizotinib can lead to serious lung issues, some patients can be safely retreated after experiencing milder symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizotinib Associated with Ground-Glass Opacity Predominant Pattern Interstitial Lung Disease: A Retrospective Observational Cohort Study with a Systematic Literature Review. Créquit, P., Wislez, M., Fleury Feith, J., et al.[2018]

Crizotinib is an effective oral treatment for ALK-rearranged non-small cell lung cancer (NSCLC), outperforming traditional chemotherapy, but most patients develop resistance within a year.

Newer ALK inhibitors like ceritinib, alectinib, brigatinib, and lorlatinib show promise in overcoming crizotinib resistance, highlighting the need for personalized treatment strategies based on individual patient responses and tumor characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tackling ALK in non-small cell lung cancer: the role of novel inhibitors. Facchinetti, F., Tiseo, M., Di Maio, M., et al.[2020]

Crizotinib is an effective treatment for non-small-cell lung cancer (NSCLC) with EML4-ALK rearrangements, showing impressive response rates in this specific population, which makes up about 3-5% of all NSCLC cases.

The drug also shows promise for NSCLC with ROS1 rearrangements, although these occur in only about 1% of cases, highlighting the importance of molecular testing to identify suitable patients for crizotinib therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizotinib. Heigener, DF., Reck, M.[2018]

Crizotinib is highly effective in treating non-small-cell lung cancer (NSCLC) with specific genetic alterations, such as EML4-ALK rearrangements and ROS1 rearrangements, which occur in 3-5% and 1% of NSCLC cases, respectively.

The drug is associated with several side effects, including visual impairment and liver enzyme elevation, and its efficacy is best predicted by detecting ALK protein through immunohistochemistry or confirming ALK rearrangements via fluorescence in situ hybridization (FISH).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizotinib. Heigener, DF., Reck, M.[2018]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Crizotinib as a personalized alternative for targeted anaplastic lymphoma kinase rearrangement in previously treated patients with non-small-cell lung cancer. [2018]

2. India pubmed.ncbi.nlm.nih.gov

Crizotinib: A comprehensive review. [2022]

3. France pubmed.ncbi.nlm.nih.gov

Crizotinib in Chinese Patients with ROS1-Rearranged Advanced Non‒Small-Cell Lung Cancer in Routine Clinical Practice. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Role of anaplastic lymphoma kinase inhibition in the treatment of non-small-cell lung cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Crizotinib in the treatment of non-small-cell lung cancer. [2018]

6. England pubmed.ncbi.nlm.nih.gov

ALK-rearranged non-small cell lung cancers: how best to optimize the safety of crizotinib in clinical practice? [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Phase II Study of Crizotinib in East Asian Patients With ROS1-Positive Advanced Non-Small-Cell Lung Cancer. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration approval: crizotinib for treatment of advanced or metastatic non-small cell lung cancer that is anaplastic lymphoma kinase positive. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Crizotinib in the treatment of non--small-cell lung cancer. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Crizotinib Associated with Ground-Glass Opacity Predominant Pattern Interstitial Lung Disease: A Retrospective Observational Cohort Study with a Systematic Literature Review. [2018]

11. China pubmed.ncbi.nlm.nih.gov

Tackling ALK in non-small cell lung cancer: the role of novel inhibitors. [2020]

12. Germany pubmed.ncbi.nlm.nih.gov

Crizotinib. [2018]

13. Germany pubmed.ncbi.nlm.nih.gov

Crizotinib. [2018]