Amivantamab + Capmatinib for Non-Small Cell Lung Cancer

(METalmark Trial)

Recruiting at 132 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Janssen Research & Development, LLC

Disqualifiers: Interstitial lung disease, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

57 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to identify the recommended Phase 2 combination dose (RP2CD\[s\]) of the amivantamab and capmatinib combination therapy in participants with non-small cell lung cancer (NSCLC) in Phase 1 (combination dose selection), and to evaluate the antitumor effect of the amivantamab and capmatinib combination therapy in mesenchymal-epithelial transition (MET) exon 14 skipping mutation and MET amplified NSCLC, when administered at the selected RP2CD(s) in Phase 2 (expansion).

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, if you are on high-dose corticosteroids, you may need to adjust your dosage to meet the trial's criteria.

What data supports the effectiveness of the drug combination Amivantamab and Capmatinib for treating non-small cell lung cancer?

Amivantamab has shown effectiveness in treating non-small cell lung cancer (NSCLC) with specific mutations, achieving a 40% response rate in patients with certain genetic profiles. It is approved for use in NSCLC patients with EGFR exon 20 insertion mutations after chemotherapy, and ongoing trials are exploring its use in combination with other drugs. ^{1 2 3 4 5}

Is Amivantamab safe for humans?

Amivantamab has been approved for use in treating certain types of lung cancer, and early studies have shown it to be safe when combined with chemotherapy. However, more data is needed to fully understand its safety in different situations. ^{2 3 6 7 8}

What makes the drug combination of Amivantamab and Capmatinib unique for treating non-small cell lung cancer?

The combination of Amivantamab and Capmatinib is unique because Amivantamab is a bispecific antibody that targets both EGFR and MET, which are proteins involved in cancer cell growth, and Capmatinib specifically targets MET. This dual targeting approach is particularly beneficial for patients with specific genetic mutations (EGFR Exon 20 insertions) in non-small cell lung cancer, offering a novel mechanism of action compared to traditional chemotherapy. ^{2 3 4 7 8}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for adults with Stage IV non-small cell lung cancer that can't be surgically removed. They should have stable brain metastases, no history of certain lung diseases or gastrointestinal issues affecting drug absorption, and controlled tumor-related pain. Participants must not need high doses of steroids and should be in good physical condition (ECOG 0 or 1).

Inclusion Criteria

I have been diagnosed with Stage IV non-small cell lung cancer that cannot be surgically removed.

My brain metastases have been treated, are stable, and I've had no symptoms for over 2 weeks.

I have had cancer before, but it won't affect this study's treatment.

Exclusion Criteria

I have brain metastases needing more steroids recently to manage symptoms.

I cannot take pills due to issues with my stomach or intestines.

I have or might have a lung condition not caused by an infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 (Combination Dose Selection)

Participants receive capmatinib 400 mg orally twice daily and amivantamab IV infusion weekly, with dose adjustments based on dose limiting toxicities

4 weeks

Weekly visits for dose adjustments

Phase 2 (Dose Expansion)

Participants receive capmatinib and amivantamab at the recommended Phase 2 combination dose to evaluate antitumor effects

Up to 2 years 1 month

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Amivantamab
• Capmatinib

Trial Overview The study tests a combination therapy using Amivantamab and Capmatinib to treat NSCLC patients with specific genetic changes (MET exon 14 skipping mutation or MET amplification). It aims to find the best dose for Phase 2 trials and assess how well tumors respond to this treatment.

Participant Groups

Group I: Phase 2 (Dose Expansion) Experimental Treatment 2 Interventions

Participants with mesenchymal-epithelial transition (MET) exon 14 skipping mutation who are treatment naïve (Cohort 1A), who have received prior therapy (Cohort 1B), or participants with MET amplification who have received prior therapy (Cohort 1C) will receive capmatinib in combination with amivantamab at the RP2CD determined by the SET in Phase 1.

Group II: Phase 1 (Combination Dose Selection) Experimental Treatment 2 Interventions

Participants will receive capmatinib 400 milligrams (mg) orally twice daily from Cycle 1 Day 1, in combination with amivantamab 700 mg intravenous (IV) infusion (for body weight less than 80 kilograms \[kg\]) or 1050 mg IV infusion (for body weight greater than or equal to 80 kg) once weekly from Cycle 1 Day 1 for 4 weeks and then every 2 weeks from Week 5 (Cycle 2; each cycle of 28 days). Doses will be escalated or de-escalated based on the dose limiting toxicities (DLTs) and the recommended Phase 2 combination dose (RP2CD) will be determined by the study evaluation team (SET).

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

Approved in United States as Rybrevant for:

• Locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations
• Locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations

Approved in European Union as Rybrevant for:

• Locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations
• Locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

Amivantamab, approved for treating non-small cell lung cancer with specific genetic mutations, works by targeting two pathways: the epithelial growth factor receptor and mesenchymal epithelial transition factor, enhancing the immune response against cancer cells.

Preclinical studies indicate that Amivantamab effectively inhibits cancer cell growth in models with exon20 insertions of the epithelial growth factor receptor, suggesting its potential as a targeted therapy for this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab: A New Hope in Targeting Non-small Cell Lung Cancer. Billowria, K., Das Gupta, G., Chawla, PA.[2023]

Amivantamab is a bispecific monoclonal antibody that targets both EGFR and MET, specifically developed for treating non-small cell lung cancer (NSCLC) with EGFR Exon 20 insertion mutations.

It received its first approval in the USA on May 21, 2021, for adult patients with advanced NSCLC who have progressed after platinum-based chemotherapy, and is currently in preregistration in multiple countries including the EU and Japan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab: First Approval. Syed, YY.[2021]

Amivantamab, a bispecific antibody targeting EGFR and MET, received accelerated FDA approval for treating non-small cell lung cancer (NSCLC) patients with specific EGFR mutations, showing a 40% objective response rate in a Phase I/IB trial with a median response duration of 11.1 months.

In patients with other EGFR mutations, amivantamab alone had a 19% response rate, while combining it with lazertinib improved the response to 36%, indicating potential benefits of combination therapy in NSCLC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab in the Treatment of Metastatic NSCLC: Patient Selection and Special Considerations. Petrini, I., Giaccone, G.[2022]

Amivantamab is the first targeted therapy approved for non-small cell lung cancer (NSCLC) patients with EGFR exon 20 insertion mutations, showing promise for a group of mutations that typically have poor outcomes.

In the CHRYSALIS phase I trial, amivantamab demonstrated efficacy through its unique mechanism as a bispecific antibody targeting both EGFR and MET, although its large size may limit effectiveness against brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab for the treatment of EGFR exon 20 insertion mutant non-small cell lung cancer. Vyse, S., Huang, PH.[2022]

Amivantamab-vmjw has shown a 40% overall response rate in patients with metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, based on a phase 1 trial involving 81 participants, indicating its efficacy after platinum-based chemotherapy.

The treatment resulted in a median progression-free survival of 8.3 months and an overall survival of 22.8 months, with an acceptable safety profile, marking it as a significant advancement for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab-Vmjw: A Novel Treatment for Patients with NSCLC Harboring EGFR Exon 20 Insertion Mutation after Progression on Platinum-Based Chemotherapy. Shah, V., McNatty, A., Simpson, L., et al.[2023]

In a phase 3 trial involving 308 patients with advanced non-small-cell lung cancer (NSCLC) and EGFR exon 20 insertions, the combination of amivantamab and chemotherapy significantly improved progression-free survival compared to chemotherapy alone, with a median of 11.4 months versus 6.7 months.

The combination therapy also showed a higher response rate, with 73% of patients achieving a complete or partial response compared to 47% in the chemotherapy-only group, indicating that amivantamab enhances the effectiveness of standard chemotherapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions. Zhou, C., Tang, KJ., Cho, BC., et al.[2023]

In a study of 61 patients with advanced EGFR-mutant NSCLC, amivantamab showed a clinical response rate of 45.2% and a disease control rate of 64.3%, indicating its potential effectiveness beyond just exon 20 insertion mutations.

The combination of amivantamab with osimertinib and concurrent radiation therapy was found to be safe, with no additional toxicities reported, suggesting that this treatment approach could be a viable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BRIEF REPORT: Real-world efficacy and safety of amivantamab for EGFR-mutant non-small cell lung cancer (NSCLC). Wang, K., Du, R., Myall, NJ., et al.[2023]

References

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

Amivantamab plus Lazertinib Is Efficacious in Non-Small Cell Lung Cancer. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Amivantamab: A New Hope in Targeting Non-small Cell Lung Cancer. [2023]

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

Amivantamab: First Approval. [2021]

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

Amivantamab in the Treatment of Metastatic NSCLC: Patient Selection and Special Considerations. [2022]

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

Amivantamab for the treatment of EGFR exon 20 insertion mutant non-small cell lung cancer. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Amivantamab-Vmjw: A Novel Treatment for Patients with NSCLC Harboring EGFR Exon 20 Insertion Mutation after Progression on Platinum-Based Chemotherapy. [2023]

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

Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions. [2023]

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

BRIEF REPORT: Real-world efficacy and safety of amivantamab for EGFR-mutant non-small cell lung cancer (NSCLC). [2023]