Amivantamab + Tepotinib for Lung Cancer

Overseen By Xiuning Le, MD,PHD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Antidepressants, Antivirals

Disqualifiers: Hepatitis B, Hepatitis C, HIV, others

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

Compensation: Varies

Number of Visits: 2

Duration: 12 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

To learn if the combination of amivantamab and tepotinib can help to control NSCLC. The safety of this drug combination will also be studied.

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 certain targeted therapies for lung cancer, like tepotinib or amivantamab, you may not be eligible for some parts of the trial.

What data supports the effectiveness of the drug Amivantamab for lung cancer?

Amivantamab has been approved for treating non-small cell lung cancer (NSCLC) with specific genetic mutations (EGFR exon 20 insertions) after other treatments have failed, showing it can help patients whose cancer has progressed despite previous chemotherapy. ^{1 2 3 4 5}

Is the combination of Amivantamab and Tepotinib safe for humans?

Amivantamab has been approved for use in non-small cell lung cancer and has shown safety in clinical trials, but it can cause infusion-related reactions in 66% of patients and other side effects like rash, nausea, and fatigue. There is no specific safety data available for the combination of Amivantamab and Tepotinib. ^{1 2 3 4 6}

How is the drug Amivantamab + Tepotinib unique for lung cancer treatment?

Amivantamab + Tepotinib is unique because it combines two targeted therapies: Amivantamab, a bispecific antibody that targets EGFR and MET proteins, and Tepotinib, which specifically targets MET. This combination is designed to treat non-small cell lung cancer (NSCLC) with specific genetic mutations, offering a novel approach for patients who have progressed after standard chemotherapy. ^{1 2 3 4 7}

Research Team

Xiuning Le, M.D., Ph.D.

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults with non-small cell lung cancer (NSCLC) that has specific genetic changes called MET alterations. They must have measurable disease, be able to take oral medication, and agree to use contraception. People who've had certain treatments or have other health issues like uncontrolled illnesses, active infections, or a history of severe lung inflammation are not eligible.

Inclusion Criteria

I have had chemotherapy or immunotherapy before.

You need to have one of these.

Your liver enzymes (AST and ALT) should be within 3 times the upper limit of normal.

Exclusion Criteria

I have not taken any MET inhibitor drugs like tepotinib or crizotinib for my condition.

I have hepatitis C or had it and completed treatment with undetectable levels now.

I have or had lung inflammation due to illness or treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

Evaluate dose-limiting toxicity (DLT) and establish the recommended phase II dose (RP2D) of amivantamab and tepotinib

4 weeks

1 visit (in-person) every 4 weeks

Treatment

Participants receive amivantamab and tepotinib to assess efficacy in MET-altered NSCLC

12 weeks

1 visit (in-person) every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Treatment Details

Interventions

• Amivantamab
• Tepotinib

Trial Overview The trial is testing the effectiveness and safety of combining two drugs: Amivantamab and Tepotinib in treating NSCLC with MET alterations. It aims to see if this drug combo can control the cancer better than current treatments.

Participant Groups

Group I: Amivantamab and Tepotinib Combination Experimental Treatment 2 Interventions

Participants will be given 2 investigational drugs (amivantamab and tepotinib) and come to the clinic for study visits every 4 weeks.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

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]

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]

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 (Rybrevant) has received accelerated FDA approval for treating adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) that has EGFR exon 20 insertion mutations, which are typically resistant to standard tyrosine kinase inhibitors (TKIs).

This approval highlights the importance of targeted therapies for specific genetic mutations in NSCLC, as patients with these mutations can benefit from alternative treatment options after failing platinum-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on Amivantamab (JNJ-61186372) for EGFR Exon 20 Insertions Positive Non-Small Cell Lung Cancer. Brazel, D., Nagasaka, M.[2021]

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 III trial involving 657 patients with advanced EGFR-mutated non-small-cell lung cancer, both amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy significantly improved progression-free survival (PFS) compared to standard chemotherapy, with median PFS of 6.3 and 8.3 months versus 4.2 months, respectively.

The combination therapies also showed a higher objective response rate (64% and 63% for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively) compared to chemotherapy (36%), although the amivantamab-lazertinib-chemotherapy regimen had more hematologic adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Passaro, A., Wang, J., Wang, Y., 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. New Zealand pubmed.ncbi.nlm.nih.gov

Amivantamab: First Approval. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

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

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

Spotlight on Amivantamab (JNJ-61186372) for EGFR Exon 20 Insertions Positive Non-Small Cell Lung Cancer. [2021]

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]

7. England pubmed.ncbi.nlm.nih.gov

Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. [2023]