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

Trial Summary

What is the purpose of this trial?

This phase II Expanded Lung-MAP treatment trial tests how well amivantamab-subcutaneous (SC) works in treating patients patients with MET amplification non-small cell lung cancer. Amivantamab-SC is a drug that reduces extra copies of the MET gene, a change present in your tumor. Giving amivantamab-SC may lower the chance of the growth or spread of advanced non-small cell lung cancer that has extra copies of the MET gene in the tumor.

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.

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

Amivantamab has been shown to be effective for patients with advanced non-small cell lung cancer (NSCLC) that have a specific mutation called EGFR Exon 20 insertion, especially after other treatments like platinum-based chemotherapy have failed. It has been approved for use in the USA and has demonstrated antitumor activity in combination with chemotherapy. ^{1 2 3 4 5}

Is amivantamab safe for humans?

Amivantamab has been approved for use in certain lung cancer patients, but it can cause side effects like infusion-related reactions, rash, and nausea. It's important to discuss potential risks with your doctor. ^{1 2 4 5 6}

How is the drug Amivantamab unique for treating non-small cell lung cancer?

Amivantamab is unique because it is a bispecific antibody that targets both EGFR and MET proteins, specifically designed for non-small cell lung cancer with EGFR Exon 20 insertion mutations, especially after other treatments like platinum-based chemotherapy have failed. ^{1 2 3 4 5}

Research Team

Shirish Gadgeel

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

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

My condition worsened after my last treatment.

I have not had radiation therapy recently.

Participants with HIV-infection must meet specific criteria

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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, 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 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]

References

1. 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]

2. 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]

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

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

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

Amivantamab: First Approval. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

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

6. United States 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. [2023]