Repotrectinib vs Crizotinib for Non-Small Cell Lung Cancer

Not currently recruiting at 298 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, repotrectinib and crizotinib, for non-small cell lung cancer (NSCLC) that has spread or is locally advanced. It focuses on patients with a specific change in their ROS1 gene who have not yet tried certain targeted drugs (TKIs). Eligible participants have NSCLC with the ROS1 change confirmed by a test and may have had one previous treatment, excluding targeted drugs. The trial aims to determine which treatment is more effective and safe. As a Phase 3 trial, it represents the final step before FDA approval, offering patients early access to potentially effective treatments.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that repotrectinib yields promising results in treating non-small cell lung cancer (NSCLC) and is generally safe. Some studies found it effective and safe for patients, though a few reported side effects, indicating that most people tolerate it well.

The FDA has already approved crizotinib for other cancers, confirming its well-known safety profile. It has been used to treat NSCLC, with side effects usually well-documented and manageable for most people.

Overall, evidence supports the safety of both treatments in humans, but individual experiences can differ. It is important to discuss potential risks and benefits with a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Repotrectinib is unique because it targets a specific mutation in non-small cell lung cancer (NSCLC) known as ROS1 or NTRK gene rearrangements, which are not addressed by many current treatments. Unlike standard options like crizotinib, which also targets ROS1, repotrectinib is designed to overcome resistance that often develops with existing therapies. This new drug also shows potential for better penetration into the central nervous system, which could be crucial for patients with brain metastases, a common complication in advanced NSCLC. Researchers are excited because these features may lead to more effective and longer-lasting responses in patients with these genetic mutations.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

This trial will compare Repotrectinib and Crizotinib for treating ROS1-positive non-small cell lung cancer (NSCLC). Research has shown that Repotrectinib, which participants in this trial may receive, is promising for treating this type of lung cancer. Studies have found that Repotrectinib works effectively and has lasting effects, even for patients who haven't tried similar treatments before. In one study, Repotrectinib effectively treated cancer that had spread to the brain. Crizotinib, another treatment option in this trial, is already known to work well for ROS1-positive NSCLC, with positive results in real-world use. Both treatments have been shown to help patients live longer and improve their health, making them strong options for managing this type of lung cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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 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 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]

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 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]

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]

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 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]

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]

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]

Citations

1. onclive.com onclive.com/view/repotrectinib-demonstrates-durable-efficacy-in-tki-naive-and--pretreated-ros1-nsclc

Repotrectinib Demonstrates Durable Efficacy in TKI-Naive ... Repotrectinib (Augtyro) showcased durable efficacy and intracranial activity in patients with ROS1-positive non–small cell lung cancer ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06315010?term=REPOTRECTINIB&viewType=Table&rank=1

REPotrectinib in ROS1-positive Non-small Cell Lung ... REPOSE is a phase II clinical trial exploring the safety and efficacy of repotrectinib in patients with non-small cell lung cancer (NSCLC) characterized by ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2302299

Repotrectinib in ROS1 Fusion–Positive Non–Small-Cell ... Repotrectinib had durable clinical activity in patients with ROS1 fusion–positive NSCLC, regardless of whether they had previously received a ROS1 TKI.

4. augtyro.com augtyro.com/ros1/study-results

AUGTYRO® ROS1+ NSCLC Study Results & Side Effects In a study of 71 people with ROS1+ lung cancer, they were given AUGTYRO as their first targeted therapy. They received AUGTYRO starting at 160 mg orally once ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11623886/

a promising new therapy for advanced nonsmall cell lung ... This study reveals the efficacy of repotrectinib, in regular clinical use with increased survival rates and tolerability outcomes, which significantly advocates ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06315010

NCT06315010 | REPotrectinib in ROS1-positive Non-small ... A Phase II Study Assessing Safety and Efficacy of REPotrectinib in ROS1-positive Non-small Cell Lung Cancer Patients With Active Brain mEtastasis (REPOSE Study).