Capmatinib Safety for Cancer

Recruiting at 7 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Novartis Pharmaceuticals

Must be taking: Capmatinib

Must not be taking: Live vaccines

Disqualifiers: Pregnancy, Nursing, Other studies, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 24

Duration: Up to 10 years

40 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess long-term safety and provide continued study treatment access to eligible participants who are judged by the Investigator to benefit from continued treatment with capmatinib monotherapy or in combination with other treatments or with the combination treatment alone in a Novartis sponsored study

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it seems that participants must already be receiving capmatinib treatment or a combination treatment to join the study.

What data supports the effectiveness of the drug Capmatinib for cancer?

Capmatinib has shown effectiveness in treating lung cancer with a specific genetic mutation (MET exon 14 skipping) by inhibiting cancer cell growth, as demonstrated in clinical studies. It has been approved for use in the USA for this type of lung cancer, and ongoing research is exploring its potential for other cancers. ^{1 2 3 4 5}

Is Capmatinib safe for humans?

Capmatinib has been studied for safety in humans, with some patients experiencing side effects like nausea, vomiting, and increased blood creatinine (a waste product in the blood). Serious side effects can include lung disease, liver toxicity, and depression, but the maximum safe dose was not reached in studies, indicating it may be generally safe at certain doses. ^{1 3 4 6 7}

How is the drug Capmatinib different from other cancer treatments?

Capmatinib is unique because it is an oral drug that specifically targets and inhibits the MET protein, which is involved in cancer cell growth, especially in cases with a specific mutation called MET exon 14 skipping. This makes it particularly effective for certain types of lung cancer, and it is being explored for use in other cancers as well. ^{1 4 6 8 9}

Research Team

Toni Wozniak, MD

Principal Investigator

Barbara Ann Karmanos Cancer Institute

Eligibility Criteria

This trial is for patients who are already part of a Novartis study and benefit from continuing Capmatinib alone or with other treatments. It's not for pregnant women, those able to become pregnant without effective contraception, or anyone receiving live vaccines recently.

Inclusion Criteria

I am currently on capmatinib treatment in a Novartis study and can move to another study.

I am willing and able to follow the study's schedule and procedures.

Written informed consent obtained prior to enrolling in the rollover study and receiving study medication. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.

Exclusion Criteria

I have not received any live vaccines in the last 30 days.

I am not on any study treatment now due to ongoing side effects.

I am not using effective birth control while on the study treatment.

Timeline

Treatment

Participants continue receiving capmatinib treatment as monotherapy or in combination with other treatments

Up to 10 years

Visits every 12 weeks for safety assessment

Safety Assessment

Safety assessment including adverse events and serious adverse events collection, local laboratory test monitoring, and local standard of care assessments

Up to 10 years

Every 12 weeks

Follow-up

Participants are monitored for safety for 30 days after the last dose of study treatment or until SAE is resolved

30 days

Treatment Details

Interventions

• Capmatinib
• Gefitinib
• Nazartinib
• Osimertinib

Trial Overview The trial continues the use of Capmatinib, either by itself or combined with Nazartinib, Gefitinib, Osimertinib. The goal is to assess long-term safety and effects when these drugs are used beyond the initial study period.

Participant Groups

Group I: Capmatinib + Osimertinib Experimental Treatment 2 Interventions

Starting dose of the study treatment for patients in this protocol should be the same as the dose provided in the parent protocol at the time when the rollover protocol is initiated. Dose modifications are permitted.

Group II: Capmatinib + Nazartinib Experimental Treatment 2 Interventions

Starting dose of the study treatment for patients should be the same as the dose provided in the parent protocol at the time when the rollover protocol is initiated. Dose modifications are permitted.

Group III: Capmatinib + Gefitinib Experimental Treatment 2 Interventions

Starting dose of the study treatment for patients in this protocol should be the same as the dose provided in the parent protocol at the time when the rollover protocol is initiated. Dose modifications are permitted.

Group IV: Capmatinib Experimental Treatment 1 Intervention

Starting dose of study treatment for patients in this protocol should be the same as the dose provided in the parent protocol at the time when the rollover protocol is initiated. Dose modifications are permitted.

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

Approved in United States as Tabrecta for:

• Metastatic non-small cell lung cancer (NSCLC) with MET exon 14 skipping

Approved in European Union as Tabrecta for:

• Metastatic non-small cell lung cancer (NSCLC) with MET exon 14 skipping

Approved in Canada as Tabrecta for:

• Metastatic non-small cell lung cancer (NSCLC) with MET exon 14 skipping

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

Capmatinib, a selective MET inhibitor, was tested in a phase I study with 44 Japanese patients having advanced solid tumors, showing a maximum tolerated dose of 400 mg twice daily for tablets, while the maximum for capsules remains undetermined.

The study reported manageable safety profiles with common side effects like increased blood creatinine and nausea, and some patients achieved stable disease, indicating potential for further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation study of capmatinib (INC280) in Japanese patients with advanced solid tumors. Esaki, T., Hirai, F., Makiyama, A., et al.[2021]

In a phase 2 study involving 20 patients with advanced NSCLC who had previously been treated with crizotinib, capmatinib showed modest efficacy, with a 10% objective response rate and an 80% disease control rate.

The study found that while capmatinib provided some benefit, particularly in patients who had discontinued crizotinib due to intolerance, resistance mechanisms such as MET mutations and MAPK alterations were common, which may limit its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 2 Study of Capmatinib in Patients With MET-Altered Lung Cancer Previously Treated With a MET Inhibitor. Dagogo-Jack, I., Moonsamy, P., Gainor, JF., et al.[2022]

Capmatinib, a MET inhibitor for treating metastatic non-small cell lung cancer, can cause severe hepatotoxicity, as demonstrated in a case where an elderly female patient developed acute hepatitis after 7 weeks of treatment, leading to a fatal outcome.

The case highlights the importance of monitoring liver function during capmatinib therapy, as hepatotoxicity is a known but infrequent adverse reaction, necessitating immediate discontinuation of the drug upon detection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe hepatotoxicity during treatment with capmatinib. Valencia Soto, CM., Martínez Callejo, V., García-Avello Fernández-Cueto, A., et al.[2023]

Capmatinib is an oral MET inhibitor specifically designed to target and inhibit cancer cell growth associated with the MET exon 14 skipping mutation, which is relevant for certain lung cancers.

In May 2020, capmatinib received FDA approval for treating adults with metastatic non-small cell lung cancer (NSCLC) that have this specific mutation, marking a significant advancement in targeted cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capmatinib: First Approval. Dhillon, S.[2021]

Capmatinib, a MET inhibitor, demonstrated significant improvements in cough and quality of life (QoL) for patients with MET exon 14-mutated advanced non-small cell lung cancer, with improvements observed as early as week 7 and sustained over time.

The median time to definitive deterioration in QoL was 16.6 months for treatment-naïve patients and 12.4 months for pre-treated patients, indicating that capmatinib not only effectively manages symptoms but also helps maintain a better quality of life for longer periods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes in capmatinib-treated patients with METex14-mutated advanced NSCLC: Results from the GEOMETRY mono-1 study. Wolf, J., Garon, EB., Groen, HJM., et al.[2023]

Capmatinib (Tabrecta) is FDA-approved for treating metastatic non-small cell lung cancer in adults with specific mutations, but patients must be monitored for serious side effects like interstitial lung disease and hepatotoxicity.

Fam-trastuzumab deruxtecan-nxki (Enhertu) has also received accelerated FDA approval for a different type of metastatic non-small cell lung cancer, with warnings about risks such as interstitial lung disease and embryo-fetal toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two New Drugs Approved for Non-Small Cell Lung Cancer. Aschenbrenner, DS.[2023]

In a phase II trial, capmatinib, a MET inhibitor, showed a high response rate of 72% in treatment-naïve patients, indicating its potential effectiveness in early-stage treatment.

For previously treated patients, the response rate was lower at 39.1%, and common side effects included peripheral edema, nausea, and vomiting, highlighting the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capmatinib Triggers Responses in NSCLC. [2019]

Two patients with advanced NSCLC and MET exon 14 mutations developed drug-induced liver injury (DILI) after receiving capmatinib following immune checkpoint inhibitor (ICI) failure, highlighting a potential safety concern with this treatment sequence.

Analysis of the FDA Adverse Event Reporting System revealed that 4.7% of capmatinib reports were associated with DILI, with serious outcomes in the majority of cases, suggesting a need for careful monitoring and further research on the safety of MET inhibitors in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capmatinib-Induced Liver Injury as Emerging Toxicity of MET Inhibitors in Patients With NSCLC Pretreated With Immune Checkpoint Inhibitors. Sisi, M., Vitale, G., Fusaroli, M., et al.[2023]

Capmatinib, an oral MET inhibitor, was well tolerated in patients with advanced MET-positive solid tumors, with a recommended phase 2 dose of 400 mg twice daily for tablets and 600 mg twice daily for capsules, achieving effective drug exposure without reaching maximum tolerated dose.

In a dose-expansion cohort of 38 patients, capmatinib demonstrated antitumor activity, with stable disease observed in various cancer types, and significant tumor reduction in patients with high MET gene copy numbers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of capmatinib in MET-positive solid tumor patients: Dose escalation and expansion of selected cohorts. Bang, YJ., Su, WC., Schuler, M., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation study of capmatinib (INC280) in Japanese patients with advanced solid tumors. [2021]

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

A Phase 2 Study of Capmatinib in Patients With MET-Altered Lung Cancer Previously Treated With a MET Inhibitor. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Severe hepatotoxicity during treatment with capmatinib. [2023]

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

Capmatinib: First Approval. [2021]

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

Patient-reported outcomes in capmatinib-treated patients with METex14-mutated advanced NSCLC: Results from the GEOMETRY mono-1 study. [2023]

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

Two New Drugs Approved for Non-Small Cell Lung Cancer. [2023]

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

Capmatinib Triggers Responses in NSCLC. [2019]

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

Capmatinib-Induced Liver Injury as Emerging Toxicity of MET Inhibitors in Patients With NSCLC Pretreated With Immune Checkpoint Inhibitors. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Phase 1 study of capmatinib in MET-positive solid tumor patients: Dose escalation and expansion of selected cohorts. [2021]