Cabozantinib for Non-Small Cell Lung Cancer

Recruiting at 6 trial locations

Overseen By Alexander Drilon, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Uncontrolled hypertension, Brain metastases, others

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

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

86 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests cabozantinib (Cabometyx), a medication designed to slow or shrink non-small cell lung cancer by targeting specific gene changes that promote cancer growth. Researchers aim to determine the drug's effectiveness and potential side effects. Participants should have advanced lung cancer with specific gene mutations, such as RET, ROS1, or NTRK fusions, or increased activity of MET or AXL. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that you cannot have taken any systemic anticancer agents within 3 weeks of starting the study. If you are on anticoagulants, you may need to adjust your treatment, as only low-dose aspirin and certain types of heparin are allowed.

Is there any evidence suggesting that cabozantinib is likely to be safe for humans?

Research has shown that cabozantinib has been tested in several types of cancer, including non-small cell lung cancer (NSCLC), medullary thyroid cancer, and prostate cancer. This testing provides a good understanding of its side effects. Cabozantinib is already approved for treating other cancers, suggesting a level of safety.

In past studies, cabozantinib was generally well-tolerated, but like many cancer drugs, it can cause side effects. Common side effects include tiredness, diarrhea, and loss of appetite. Some patients also experienced high blood pressure and hand-foot syndrome, which causes redness and swelling on the palms and soles. While these side effects can be managed, anyone considering joining the trial should discuss them with their doctor.

This study is in phase 2, focusing on how well the drug works for this specific cancer and gathering more safety information. The fact that cabozantinib has passed earlier study phases for other cancers enhances understanding of its safety profile. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for non-small cell lung cancer?

Cabozantinib is unique because it targets specific genetic mutations and overexpressions in non-small cell lung cancer (NSCLC), unlike many current treatments that focus on general chemotherapy or immunotherapy. It works by inhibiting multiple tyrosine kinases, including RET, NTRK, MET, AXL, and ROS1 fusions, which are crucial for tumor growth and spread. This targeted approach offers potential for more personalized and effective treatment options, particularly for patients whose tumors have these specific genetic alterations. Researchers are excited about cabozantinib because it addresses unmet needs in NSCLC treatment by potentially offering benefits to patients who do not respond well to existing therapies.

What evidence suggests that cabozantinib might be an effective treatment for non-small cell lung cancer?

Research shows that cabozantinib can treat certain cancers by shrinking tumors through targeting specific gene changes in cancer cells. This trial studies cabozantinib's effectiveness in non-small cell lung cancer (NSCLC) patients with specific genetic alterations. Patients will be grouped based on their tumor's genetic profile: those with RET fusion, NTRK fusion, MET or AXL overexpression, amplification, or mutation, and ROS1 fusion. Cabozantinib has shown promise in shrinking tumors and, in some cases, stopping cancer growth in patients with these gene changes. Additionally, cabozantinib has been effective in treating other cancers, such as medullary thyroid and prostate cancer, suggesting its potential for NSCLC. ^{1 3 4 6 7}

Who Is on the Research Team?

Alexander Drilon, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults with advanced non-small cell lung cancer that is metastatic or unresectable and have specific genetic changes (RET, ROS1, NTRK fusions, MET or AXL overexpression/amplification/mutation). Must be able to perform daily activities well (Karnofsky >70%), have good organ function, not pregnant, agree to use contraception. Excludes those with recent significant illnesses/treatments or known allergies to cabozantinib.

Inclusion Criteria

I understand the study requirements and have signed the consent form.

Your disease can be measured using a specific set of guidelines called RECIST1.1.

I am able to care for myself and engage in normal activities.

Exclusion Criteria

I have had serious bleeding or a tumor affecting major blood vessels in the last 28 days.

I have been treated with cabozantinib before.

I haven't had radiation for bone or brain cancer, or any radiation treatment, in the last 2 to 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cabozantinib to assess its effects on tumors with RET, ROS1, or NTRK fusion, or increased MET or AXL activity

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Cabozantinib

Trial Overview The trial tests the effects of an oral drug called Cabozantinib on patients with certain gene changes in their lung cancer cells. It's a phase II study which means it focuses on how effective this treatment is and monitors side effects closely.

How Is the Trial Designed?

Group I: Cabozantinib Experimental Treatment 1 Intervention

This will be a single-institution, open label, two-stage, single agent trial of cabozantinib in patients with advanced NSCLCs.atients in GROUP A will have tumors with a RET fusion. Patients in GROUP B will have tumors with an NTRK fusion, or MET or AXL overexpression, amplication, or mutatation. Patients in GROUP C will have tumors with a ROS1 fusion. Patients in GROUP D will have tumors with a RET fusion and have progressed on a selective RET TKI.

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

Approved in European Union as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in United States as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Canada as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Japan as Cabometyx for:

• Renal cell carcinoma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Exelixis

Industry Sponsor

Trials

126

Recruited

20,500+

Michael M. Morrissey

Exelixis

Chief Executive Officer since 2010

PhD in Chemistry from Harvard University, BSc in Chemistry from the University of Wisconsin

Vicki L. Goodman

Exelixis

Chief Medical Officer since 2022

MD

Published Research Related to This Trial

Osimertinib, a third-generation EGFR-tyrosine kinase inhibitor, was effective for 2.5 years in a 78-year-old woman with T790M-positive lung cancer, but she eventually experienced disease progression due to the emergence of a new resistance mutation (C797G).

The case highlights the potential of liquid biopsy and next-generation sequencing to monitor clonal evolution and identify novel resistance mechanisms in patients treated with osimertinib, which could inform future treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acquired EGFR C797G Mutation Detected by Liquid Biopsy as Resistance Mechanism After Treatment With Osimertinib: A Case Report. DE Carlo, E., Schiappacassi, M., Pelizzari, G., et al.[2022]

In a study of 15 patients with non-small-cell lung cancer (NSCLC) having MET exon 14 skipping mutations, treatment with MET inhibitors crizotinib and cabozantinib showed promising results, with 50% of treated patients experiencing a partial response.

The presence of METex14 mutations was noted without other actionable mutations, indicating that these mutations can be significant drivers of NSCLC and are responsive to targeted therapies, although some patients experienced side effects requiring treatment adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case series of MET exon 14 skipping mutation-positive non-small-cell lung cancers with response to crizotinib and cabozantinib. Wang, SXY., Zhang, BM., Wakelee, HA., et al.[2020]

Crizotinib, an ALK inhibitor, has been established as a new standard of care for advanced ALK-positive non-small cell lung cancer (NSCLC) due to its significant efficacy and favorable safety profile observed in phase I, II, and III trials.

Most adverse events associated with crizotinib are mild to moderate, and with proper monitoring and supportive care, dose interruptions can often be avoided, allowing patients to continue benefiting from the treatment even after initial disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of crizotinib therapy for ALK-rearranged non-small cell lung carcinoma: an expert consensus. Cappuzzo, F., Moro-Sibilot, D., Gautschi, O., et al.[2018]

Osimertinib, an EGFR inhibitor, shows promise as an effective treatment for patients with untreated non-small cell lung cancer that has spread to the brain.

In clinical studies, osimertinib demonstrated longer median progression-free survival and higher objective response rates compared to older EGFR inhibitors like gefitinib and erlotinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib Treats CNS Metastases in NSCLC. [2022]

In a study of 542 non-small-cell lung cancer patients, high plasma trough levels of the kinase inhibitor alectinib were associated with a significantly higher risk of dose-limiting toxicities (DLTs), with 64% of patients in the high group experiencing DLTs compared to 29% in the non-high group.

For other kinase inhibitors like crizotinib, osimertinib, dabrafenib, and trametinib, no significant differences in DLTs were found between high and non-high plasma trough level groups, indicating that alectinib may have a unique risk profile among these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Relevance of High Plasma Trough Levels of the Kinase Inhibitors Crizotinib, Alectinib, Osimertinib, Dabrafenib, and Trametinib in NSCLC Patients. Lin, L., Barkman, HJ., Smit, EF., et al.[2023]

A study of 130 treatment courses in 111 patients revealed that safety monitoring activities (SMAs) for EGFR and ALK inhibitors were inconsistently conducted, with prevalence ranging from 10.0% to 84.6%, and 31.5% of courses had no SMAs performed.

EGFR inhibitors were associated with a higher likelihood of SMAs being conducted compared to ALK inhibitors, highlighting the need for clinicians to closely follow FDA guidelines to ensure patient safety and monitor for serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Monitoring Activity During EGFR or Anaplastic Lymphoma Kinase Inhibitor Therapy for Patients With Lung Cancer. Singh, AM., Rubiera-Pebe, R., Ahmad, Y., et al.[2023]

Cabozantinib (Cabometyx) has received approval for the treatment of locally advanced or metastatic differentiated thyroid cancer that has not responded to previous therapies targeting vascular endothelial growth factor receptors.

This approval highlights Cabozantinib's efficacy in addressing a specific type of thyroid cancer that has progressed after other treatments, providing a new option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Indication for Cabozantinib. Aschenbrenner, DS.[2023]

Osimertinib, an irreversible tyrosine kinase inhibitor, showed excellent activity in treating a 69-year-old man with metastatic EGFR-mutated non-small cell lung cancer, leading to a rapid treatment response despite initial severe pancytopenia.

After experiencing pancytopenia, the patient's dose of osimertinib was reduced from 80 mg to 40 mg daily, which allowed for continued effective treatment without further adverse events, demonstrating the potential for safe dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancytopenia During Osimertinib Treatment in a Patient with EGFR-Mutated Non-Small Cell Lung Cancer. Di Marino, P., Chiapperino, C., Primavera, FC., et al.[2022]

A 72-year-old male patient developed significant cardiac toxicities, including QTc prolongation, atrial fibrillation, and heart failure, after 15 months of osimertinib therapy for metastatic non-small cell lung cancer, highlighting the potential cardiac risks associated with this treatment.

Management strategies included discontinuing rosuvastatin, which can exacerbate QTc prolongation, and initiating medications for atrial fibrillation and heart failure, suggesting the need for careful monitoring and risk assessment in patients receiving osimertinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple cardiotoxicities during osimertinib therapy. Kobat, H., Davidson, M., Elkonaissi, I., et al.[2023]

A 60-year-old male patient with advanced non-small cell lung cancer (NSCLC) developed early-onset interstitial pneumonitis just two days after starting a combination treatment of crizotinib and osimertinib, highlighting a significant safety concern.

This case underscores the risk of interstitial pneumonitis associated with both crizotinib and osimertinib, particularly in patients with elevated MET copy number amplification who may be resistant to osimertinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early-onset interstitial pneumonitis in a patient with advanced non-small cell lung cancer treated with crizotinib and osimertinib. Cheng, Y., Yu, Q., Xiong, Y., et al.[2022]

Osimertinib significantly improves progression-free survival (PFS) in patients with metastatic non-small cell lung cancer (NSCLC) with the EGFR T790M mutation, showing a median PFS of 10.1 months compared to 4.4 months with chemotherapy in a trial of 419 patients.

The safety profile of osimertinib is favorable compared to other EGFR tyrosine kinase inhibitors and chemotherapy, with common side effects including diarrhea and rash, making it a viable treatment option for patients who have progressed on previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Benefit-Risk Assessment of Osimertinib for the Treatment of Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor T790M Mutation. Odogwu, L., Mathieu, L., Goldberg, KB., et al.[2022]

Cabozantinib (Cabometyx) is an effective treatment for advanced renal cell carcinoma, targeting specific pathways to inhibit tumor growth.

Glycopyrrolate/formoterol fumarate (Bevespi Aerosphere) is used to manage chronic obstructive pulmonary disease (COPD) by relaxing airway muscles and improving breathing, while ephedrine sulfate (Akovaz) is utilized to treat hypotension during anesthesia, helping to stabilize blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical Approval Update. Choy, M.[2020]

Cabozantinib demonstrated clinical activity in patients with non-small-cell lung carcinoma (NSCLC), showing a 10% objective response rate and a 38% overall disease-control rate after 12 weeks of treatment, particularly in patients with KRAS mutations.

The treatment was associated with manageable safety concerns, with common grade 3/4 adverse events including fatigue and palmar-plantar erythrodysesthesia, although there was one serious treatment-related adverse event (hemorrhage) reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a Phase II Placebo-controlled Randomized Discontinuation Trial of Cabozantinib in Patients with Non-small-cell Lung Carcinoma. Hellerstedt, BA., Vogelzang, NJ., Kluger, HM., et al.[2019]

Cabozantinib is an effective treatment for advanced hepatocellular carcinoma (HCC) after failure of sorafenib, showing significant improvement in overall survival and progression-free survival compared to placebo in the phase 3 CELESTIAL trial.

Common side effects of cabozantinib include palmar-plantar erythrodysesthesia, hypertension, fatigue, and diarrhea, which are important to manage in patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib for the Treatment of Advanced Hepatocellular Carcinoma: Current Data and Future Perspectives. Trojan, J.[2021]

Cabozantinib is an oral multitargeted tyrosine kinase inhibitor approved for advanced renal cell carcinoma and progressive metastatic medullary thyroid cancer, showing potential advantages over single-receptor TKIs.

The article reviews clinical trial data and management strategies for common adverse events associated with cabozantinib, highlighting its expanding use in treating various cancers such as prostate, hepatocellular, and lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib: A Multitargeted Oral Tyrosine Kinase Inhibitor. Markowitz, JN., Fancher, KM.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12394869/

Analysis of the Efficacy and Safety of Cabozantinib ... These drugs enhance patient survival by specifically targeting cancer cells while minimizing damage to healthy tissues. The current research ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.8645

Final results of a phase II study of cabozantinib in patients ... This is a single-arm, phase 2 trial in which patients with metastatic MET-altered lung cancers received cabozantinib (60 mg daily) until disease progression or ...

3. ipsen.com ipsen.com/press-releases/asco-2022-new-cabometyx-data-show-encouraging-results-in-monotherapy-and-in-combination-across-different-tumor-types-including-metastatic-non-small-cell-lung-cancer/

ASCO 2022: New Cabometyx® data show encouraging ... These data show that the therapeutic potential of Cabometyx as a key treatment option in a broad range of tumors is continuing to be realized.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01639508

NCT01639508 | Cabozantinib in Patients With RET Fusion- ... Cabozantinib has been studied and shown to cause cancer shrinkage in other cancers such as medullary thyroid cancer and prostate cancer. We thus have a good ...

5. jtocrr.org jtocrr.org/article/S2666-3643(25)00074-8/fulltext

A Phase II Study of Cabozantinib in Patients With MET ... Importantly, we demonstrated that cabozantinib, a type II MET TKI, could benefit patients with MET-altered lung cancers previously treated with type I MET TKIs.

6. opdivohcp.com opdivohcp.com/safety/rcc/opdivo-cabometyx

OPDIVO® (nivolumab) + CABOMETYX® (cabozantinib) Safety ... OPDIVO® (nivolumab) is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum- ...

7. ir.exelixis.com ir.exelixis.com/news-releases/news-release-details/exelixis-provides-update-phase-3-contact-01-trial-evaluating

Exelixis Provides Update on Phase 3 CONTACT-01 Trial ... Exelixis Provides Update on Phase 3 CONTACT-01 Trial Evaluating Cabozantinib in Combination with Atezolizumab in Patients with Metastatic Non-Small Cell Lung ...