Amivantamab for Non-Small Cell Lung Cancer

Recruiting at 98 trial locations

Overseen By SWOG Network Operations Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: SWOG Cancer Research Network

Must not be taking: MET TKIs, Anti-PD-1, Anti-PD-L1

Disqualifiers: Other oncogenic alterations, Active infection, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: Up to 3 years

88 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a new drug, amivantamab-SC (a form of amivantamab-vmjw), in treating non-small cell lung cancer (NSCLC) with extra copies of the MET gene. Amivantamab-SC aims to reduce these extra copies, potentially stopping the cancer from growing or spreading. It targets individuals whose tumors have this MET amplification and who have already tried other treatments for advanced NSCLC. Participants should not have other known cancer mutations and must have experienced disease progression after their last therapy.

As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer treatment.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you must not have received any systemic therapy, like chemotherapy or immunotherapy, within 21 days before joining the study, and you cannot receive any other cancer treatments while participating.

Is there any evidence suggesting that amivantamab-vmjw is likely to be safe for humans?

Research has shown that amivantamab is generally safe for patients. It is already approved to treat certain types of lung cancer with specific gene changes, indicating its safety for humans. Studies have found that amivantamab can effectively treat non-small cell lung cancer with certain genetic mutations. Although some side effects have been reported, they are usually manageable. Discussing potential risks and benefits with a healthcare provider is important before joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Amivantamab is unique because it’s a bispecific antibody designed to target specific proteins, EGFR and MET, which are often involved in the growth of non-small cell lung cancer cells. Unlike traditional chemotherapy that attacks rapidly dividing cells indiscriminately, amivantamab specifically homes in on these cancer-driving proteins, potentially leading to fewer side effects and improved effectiveness. Researchers are particularly excited about its subcutaneous delivery method, which can offer more convenience and comfort compared to the intravenous administration of many current treatments.

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

Research shows that amivantamab can help treat non-small cell lung cancer (NSCLC) with certain genetic changes. In earlier studies, it effectively treated patients with advanced NSCLC who had changes in the EGFR gene. Early results also suggest that amivantamab might work on tumors with extra copies of the MET gene, which is the focus of this trial. Participants will receive amivantamab to evaluate its effectiveness on tumors with more MET genes. Amivantamab blocks these genetic changes, potentially slowing or stopping cancer cell growth. While this trial focuses on tumors with more MET genes, the drug has already shown promise in similar lung cancers. ^{1 2 6 7 8}

Who Is on the Research Team?

Shirish Gadgeel

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for adults with advanced non-small cell lung cancer that has extra copies of the MET gene. They must have measurable disease, no other actionable cancer mutations, and should have tried at least one systemic treatment before. Participants need a recent CT or MRI scan and stable brain metastases if present.

Inclusion Criteria

Participants must meet specific laboratory criteria

Participants with HIV-infection must meet specific criteria

My condition worsened after my last treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive amivantamab subcutaneously on days 1, 8, 15, and 22 of cycle 1 and then on days 1 and 15 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 3 years

4 visits in cycle 1, 2 visits in subsequent cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Amivantamab-vmjw

Trial Overview The trial tests amivantamab-vmjw's effectiveness in treating lung cancer with MET amplification. It involves imaging tests like MRI and CT scans to monitor the disease, as well as collecting biospecimens to understand how the drug works.

How Is the Trial Designed?

Group I: Treatment (amivantamab) Experimental Treatment 4 Interventions

Patients receive amivantamab SC on days 1, 8, 15, and 22 of cycle 1 and then on days 1 and 15 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI and collection of blood samples throughout the trial.

Amivantamab-vmjw 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 whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor

Approved in European Union as Rybrevant for:

• Non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) exon 20 insertion mutations

Who Is Running the Clinical Trial?

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Amivantamab received accelerated FDA approval for treating advanced non-small cell lung cancer (NSCLC) with specific EGFR exon 20 insertion mutations, showing a 40% overall response rate and a median response duration of 11.1 months in an ongoing clinical trial with multiple cohorts.

The treatment is associated with a high incidence of infusion-related reactions (66%), along with other common side effects like rash and fatigue, highlighting the importance of monitoring patients during administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Amivantamab for the Treatment of Patients with Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations. Chon, K., Larkins, E., Chatterjee, S., 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]

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 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, 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]

Citations

1. investor.jnj.com investor.jnj.com/investor-news/news-details/2025/Data-published-in-The-New-England-Journal-of-Medicine-demonstrate-RYBREVANT-amivantamab-vmjw-plus-LAZCLUZE-lazertinib-is-re-setting-survival-expectations-in-first-line-EGFR-mutated-lung-cancer/default.aspx

News Details - JNJ Investor Relations Chemotherapy-free combination regimen ushers in new era for first-line treatment, with overall survival projected to exceed four years, ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2306441

Amivantamab plus Chemotherapy in NSCLC with EGFR ... Amivantamab has been approved for the treatment of patients with advanced non–small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38205202/

Effectiveness and safety of amivantamab in EGFR exon 20 ... The efficacy of amivantamab was confirmed for the real-world population for EGFR E20I-mutated NSCLC. PD-L1 status could be a poor predictive factor.

4. jnj.com jnj.com/media-center/press-releases/rybrevant-amivantamab-vmjw-plus-lazcluze-lazertinib-outperforms-osimertinib-with-a-significant-and-unprecedented-overall-survival-benefit-in-patients-with-egfr-mutated-non-small-cell-lung-cancer

RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE™ ... Median overall survival not yet reached with projected improvement of more than one year versus osimertinib.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e20646

Real-world treatment patterns and outcomes among ... Amivantamab and lazertinib in treatment-naïve EGFR-mutated advanced non–small-cell lung cancer (NSCLC): Long-term follow-up and ctDNA results ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39336976/

Efficacy and Safety of Amivantamab in Advanced or ... Current evidence suggests that amivantamab is an effective treatment option for patients with advanced or metastatic NSCLC with EGFR mutations.

7. rybrevanthcp.com rybrevanthcp.com/

RYBREVANT® (amivantamab-vmjw) HCP The official healthcare provider website for RYBREVANT® (amivantamab-vmjw), a treatment for EGFR+ mNSCLC. See Full Prescribing & Safety Info.

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0169500225006580

Real-world efficacy and safety of amivantamab in EGFR ... Amivantamab is a bispecific anti-EGFR–MET antibody approved to treat non-small cell lung cancers (NSCLCs) harbouring EGFR exon 20 insertions (EGFR-exon20ins).