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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a combination of two drugs, amivantamab (a monoclonal antibody) and tepotinib (a MET inhibitor), can control advanced or metastatic non-small cell lung cancer (NSCLC). Researchers aim to ensure the safety of this combination for participants. Individuals with NSCLC who have specific MET gene changes and have undergone frequent doctor visits or treatments might be suitable candidates. Participants will take the drugs and visit the clinic every four weeks to monitor progress. As a Phase 1, Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

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.

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

Previous studies have shown that amivantamab is effective for patients with certain types of lung cancer. It has been used in patients with advanced non-small cell lung cancer (NSCLC) and is generally well-tolerated. Research indicates that combining amivantamab with other drugs does not increase side effects, which supports its safety profile.

There is less direct information about using amivantamab and tepotinib together. However, extensive studies on amivantamab alone have reported no major safety issues, suggesting it is reasonably safe when combined with other treatments.

The safety of tepotinib is not specifically detailed in the provided sources, but the trial's phase indicates that the safety of the combination is still under exploration. Treatments in early testing stages are typically closely monitored for any side effects.

Participants considering joining the trial can find some reassurance in the existing safety data for amivantamab and the ongoing monitoring of the combination's safety in the study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of amivantamab and tepotinib for lung cancer because these drugs work in a novel way compared to current treatments. Unlike standard therapies that often target cancer broadly, amivantamab is a bispecific antibody that specifically targets both the EGFR and MET pathways, which are crucial in certain lung cancers. Tepotinib, on the other hand, specifically inhibits the MET receptor, potentially preventing the cancer from growing and spreading. Together, these drugs might offer a more targeted attack on cancer cells, potentially leading to better outcomes for patients with fewer side effects.

What evidence suggests that the combination of amivantamab and tepotinib could be effective for lung cancer?

Research has shown that amivantamab holds promise for treating non-small cell lung cancer (NSCLC), particularly in patients with specific EGFR mutations. Studies found that combining amivantamab with chemotherapy significantly reduces the risk of cancer progression. Tepotinib has proven effective for NSCLC patients with MET exon 14 skipping mutations. In this trial, participants will receive a combination of amivantamab and tepotinib, targeting both EGFR and MET pathways, which are often involved in cancer growth. This dual targeting may improve outcomes in controlling NSCLC, based on the individual efficacy of these drugs. ^{2 3 6 7 8}

Who Is on the Research Team?

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

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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, 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 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]

Citations

1. jnj.com jnj.com/media-center/press-releases/rybrevant-amivantamab-vmjw-in-combination-with-chemotherapy-is-the-first-fda-approved-therapy-for-first-line-treatment-of-patients-with-non-small-cell-lung-cancer-with-egfr-exon-20-insertion-mutations

RYBREVANT® (amivantamab-vmjw) in Combination With ... RYBREVANT plus chemotherapy is the first targeted approach approved for the first-line treatment of patients with NSCLC with EGFR exon 20 insertion mutations.

2. 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 ...

3. jnj.com jnj.com/media-center/press-releases/rybrevant-amivantamab-vmjw-plus-standard-of-care-approved-in-the-u-s-as-first-and-only-targeted-regimen-to-cut-risk-of-disease-progression-by-more-than-half-in-second-line-egfr-mutated-advanced-lung-cancer

RYBREVANT® (amivantamab-vmjw) plus standard of care ... The US Food and Drug Administration (FDA) approved RYBREVANT (amivantamab-vmjw) in combination with standard of care chemotherapy (carboplatin and pemetrexed)

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11432208/

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

5. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-amivantamab-vmjw-carboplatin-and-pemetrexed-non-small-cell-lung-cancer-egfr-exon-19

FDA approves amivantamab-vmjw with carboplatin and ... FDA approves amivantamab-vmjw with carboplatin and pemetrexed for non-small cell lung cancer with EGFR exon 19 deletions or L858R mutations.

6. investor.jnj.com investor.jnj.com/investor-news/news-details/2024/RYBREVANT-amivantamab-vmjw-plus-chemotherapy-shows-positive-overall-survival-trend-versus-chemotherapy-in-patients-with-previously-treated-EGFR-mutated-lung-cancer/default.aspx

RYBREVANT® (amivantamab-vmjw) plus chemotherapy ... Post-progression outcomes showed significant and sustained improvement for RYBREVANT® plus standard of care versus chemotherapy alone.

7. jto.org jto.org/article/S1556-0864(25)00772-5/fulltext

A Promising Treatment for NSCLC With Exon 14 Skipping ... Preliminary results regarding the safety profile of amivantamab plus capmatinib revealed no additive MET-related toxicity.

8. jnjmedicalconnect.com jnjmedicalconnect.com/products/rybrevant/medical-content/use-of-rybrevant-in-metastatic-nsclc-with-met-mutations-or-amplifications

Use of RYBREVANT in Metastatic NSCLC With MET ... A summary of available data on the use of RYBREVANT (amivantamab) in patients with metastatic NSCLC and MET mutations.