Amivantamab + Capmatinib for Non-Small Cell Lung Cancer

(METalmark Trial)

Not currently recruiting at 157 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find the best dose and evaluate the effectiveness of a new combination of two drugs, amivantamab (a monoclonal antibody) and capmatinib (a kinase inhibitor), for treating non-small cell lung cancer, which doesn't respond well to surgery. In the first phase, researchers will determine the ideal dose combination. In the second phase, they will test this combination on patients with specific genetic changes in their cancer, such as the MET exon 14 skipping mutation. Individuals with non-small cell lung cancer that has spread and who have been stable with low-dose steroid treatment for more than two weeks might be suitable for this trial. As a Phase 1/Phase 2 trial, this study focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment research.

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.

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

Research has shown that amivantamab, when used alone, has strong and lasting effects against certain types of advanced non-small cell lung cancer (NSCLC). Patients with specific genetic changes in their cancer, known as MET exon 14 mutations, responded well to this treatment. When combined with capmatinib, studies in similar NSCLC patients have shown promising results.

Regarding safety, previous patients generally tolerated amivantamab well, although some experienced side effects. Common side effects included skin reactions and reactions during the drug infusion, such as fever or chills. Capmatinib has also been tested and showed good results, but it can cause side effects like nausea and tiredness.

Overall, past studies have tested the combination of amivantamab and capmatinib and found it safe for many people with NSCLC. However, individual responses vary, so consulting a healthcare professional is important to understand personal implications. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about amivantamab and capmatinib for non-small cell lung cancer (NSCLC) because they target specific genetic mutations linked to this cancer type. Unlike traditional chemotherapy, which attacks all rapidly dividing cells, amivantamab is a bispecific antibody that targets both the EGFR and MET pathways, offering a more precise treatment approach. Capmatinib is a MET inhibitor that specifically targets the MET exon 14 skipping mutation or MET amplification, which are known drivers of NSCLC. This targeted approach could lead to more effective treatments with potentially fewer side effects compared to existing options.

What evidence suggests that the amivantamab and capmatinib combination could be effective for non-small cell lung cancer?

Research has shown that amivantamab, when used alone, effectively treats advanced non-small cell lung cancer (NSCLC) with specific genetic changes called MET exon 14 skipping mutations. One study found that 82% of patients experienced tumor shrinkage. Capmatinib also works well against cancers driven by MET changes. In this trial, participants will receive a combination of amivantamab and capmatinib. Early research combining these treatments has shown promising results for patients with these genetic changes in NSCLC. This combination aims to fight cancer more effectively by targeting specific genetic changes in tumors. Overall, these findings suggest that using both amivantamab and capmatinib could successfully treat this type of lung cancer. ^{2 3 5 6 7}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05488314

NCT05488314 | A Study of Amivantamab and Capmatinib ... The purpose of this study is to identify the recommended Phase 2 combination dose (RP2CD[s]) of the amivantamab and capmatinib combination therapy in ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.8619

Amivantamab plus capmatinib in advanced non-small cell ... Ami monotherapy has demonstrated meaningful clinical activity in MET-driven advanced NSCLC, including in patients (pts) harboring MET exon 14 ...

3. jto.org jto.org/article/S1556-0864(25)00720-8/fulltext

Amivantamab in Participants With Advanced NSCLC and ... We assessed the safety and efficacy of amivantamab in participants with advanced NSCLC harboring primary MET exon 14 skipping mutations (METex14). Methods.

4. jnj.com jnj.com/media-center/press-releases/subcutaneous-amivantamab-delivers-promising-45-percent-overall-response-rate-with-median-duration-of-7-2-months-in-recurrent-or-metastatic-head-and-neck-cancer

Subcutaneous amivantamab delivers promising 45 percent ... Responses were rapid and durable, and tumor shrinkage was observed in 82 percent of patients New findings from this investigational study ...

5. jnjmedicalconnect.com jnjmedicalconnect.com/products/rybrevant/medical-content/use-of-rybrevant-in-combination-with-capmatinib

Use of RYBREVANT in Combination With Capmatinib Amivantamab plus capmatinib in advanced non-small cell lung cancer (NSCLC) harboring MET alterations: recommended phase 2 combination dose ...

6. investor.jnj.com investor.jnj.com/investor-news/news-details/2025/RYBREVANT-amivantamab-vmjw-plus-LAZCLUZE-lazertinib-prevents-acquired-resistance-versus-osimertinib-in-first-line-EGFR-mutated-non-small-cell-lung-cancer/default.aspx

RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE ... An analysis of the efficacy and safety of LAZCLUZE® from the Phase 3 LASER301 study was published in The Journal of Clinical Oncology in 2023.26.

7. sciencedirect.com sciencedirect.com/science/article/pii/S1556086425007208

Amivantamab in Participants With Advanced NSCLC and ... Amivantamab demonstrated clinically meaningful and durable antitumor activity in participants with METex14 advanced NSCLC, including those who progressed on ...