Premedication for Amivantamab + Lazertinib in Non-Small Cell Lung Cancer

Not currently recruiting at 61 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Janssen Research & Development, LLC

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

Disqualifiers: Interstitial lung disease, Symptomatic brain metastases, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 cycles (each cycle 28 days)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if taking certain medications before starting treatment with amivantamab (a monoclonal antibody) and lazertinib can reduce infusion-related reactions, which are side effects from the first dose given intravenously. The medications being tested—dexamethasone, montelukast, and methotrexate—are administered to different groups to identify the most effective option. This study targets individuals with advanced non-small cell lung cancer who have a specific gene mutation (EGFR mutation) and have previously tried treatments like osimertinib and chemotherapy. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for this trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that amivantamab is approved to treat certain types of non-small cell lung cancer (NSCLC), indicating its safety for that specific use.

Some patients have experienced reactions during amivantamab infusion, such as fever, chills, and nausea. Medication or adjustments in administration usually manage these reactions.

Prospective clinical trial participants should understand that while approval for one condition suggests some safety, side effects may still occur when used for other purposes or with other treatments. Discuss any concerns with the trial team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the potential of Amivantamab combined with Lazertinib for non-small cell lung cancer because this duo targets cancer in a unique way. Unlike traditional treatments, which often focus on a single pathway, Amivantamab is a bispecific antibody that can simultaneously target EGFR and MET pathways, both of which are involved in cancer growth and resistance. Meanwhile, Lazertinib is an oral inhibitor specifically designed to tackle EGFR mutations with greater precision and fewer side effects. This combination promises not only to address the cancer more effectively but also to potentially overcome resistance seen with current therapies.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research has shown that combining amivantamab and lazertinib effectively treats non-small cell lung cancer (NSCLC) with specific genetic changes. In this trial, participants will receive a combination therapy of IV amivantamab and oral lazertinib. Studies indicate that this combination outperforms lazertinib alone for patients with these genetic changes. Specifically, the combination has been linked to longer survival, with some patients living over four years. This treatment aims to redefine expectations for initial treatments of this lung cancer type. Overall, the combination is considered a promising option for improving outcomes in these patients. ^{6 7 8 9 10}

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 advanced or metastatic non-small cell lung cancer (NSCLC) that has specific EGFR mutations, and who have already been treated with osimertinib and chemotherapy. Participants should be in good physical condition (ECOG grade 0 or 1), not have symptomatic brain metastases, unresolved severe side effects from previous treatments, a history of certain lung diseases, or recent treatment with similar drugs.

Inclusion Criteria

I am using an additional barrier method along with oral contraceptives.

I am fully active or can carry out light work.

I will use a condom during and 3 months after the study treatments.

Exclusion Criteria

I have brain metastases but am stable and not on steroids for at least 2 weeks.

I haven't taken anti PD-1 or PD-L1 drugs in the last 6 weeks and any rash from previous treatments has healed.

Side effects from my previous cancer treatments have mostly gone away.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive premedication with dexamethasone, montelukast, or methotrexate prior to amivantamab infusion to reduce infusion-related reactions

3 cycles (each cycle 28 days)

Multiple visits per cycle for infusion and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 30 days after end of treatment

What Are the Treatments Tested in This Trial?

Interventions

• Amivantamab

Trial Overview The study tests if premedication with dexamethasone, montelukast, or methotrexate can reduce reactions to the first dose of amivantamab infusion. Amivantamab is given through an IV alongside oral lazertinib to see how well they work together against NSCLC after other treatments have failed.

How Is the Trial Designed?

Group I: Background Anti-cancer Therapy with Amivantamab Plus Lazertinib Experimental Treatment 5 Interventions

Participant will receive following treatments in 4 different cohorts prior to administration of combination therapy of IV Amivantamab and oral Lazertinib (anti-cancer regimen): dexamethasone dose-1 in Cohort A; dexamethasone dose-2 in Cohort A2; montelukast in Cohort B; and methotrexate in Cohort C.

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

The ongoing CHRYSALIS study shows that the combination of amivantamab, an EGFR-MET bispecific antibody, and lazertinib, a third-generation EGFR TKI, is effective in treating both treatment-naive patients and those who have relapsed after osimertinib.

The MARIPOSA study is a phase 3 trial designed to compare the safety and efficacy of the amivantamab and lazertinib combination therapy against single-agent osimertinib, aiming to improve first-line treatment outcomes for patients with EGFR-mutant non-small-cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MARIPOSA: phase 3 study of first-line amivantamab + lazertinib versus osimertinib in EGFR-mutant non-small-cell lung cancer. Cho, BC., Felip, E., Hayashi, H., et al.[2022]

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, 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]

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 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]

The combination of amivantamab and lazertinib showed a 36% overall response rate in patients with EGFR-mutant non-small cell lung cancer who had progressed on previous treatments, indicating potential efficacy in a challenging treatment setting.

The safety profile of the combination therapy was consistent with previous studies, with only 4% of patients experiencing severe side effects, suggesting that this treatment may be safe for patients who are chemotherapy naive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab plus lazertinib in osimertinib-relapsed EGFR-mutant advanced non-small cell lung cancer: a phase 1 trial. Cho, BC., Kim, DW., Spira, AI., et al.[2023]

Citations

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Data published in The New England Journal of Medicine ... Chemotherapy-free combination regimen ushers in new era for first-line treatment, with overall survival projected to exceed four years, ...

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A cost-effectiveness analysis of amivantamab plus ... This study evaluates the cost-effectiveness of AL regimen compared with osimertinib in US and Chinese healthcare settings.

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nct04487080 | A Study of Amivantamab and Lazertinib ... The purpose of this study is to assess the efficacy of the amivantamab and lazertinib combination, compared with osimertinib, in participants with epidermal ...

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Primary Results From the Phase III PALOMA-3 Study Phase III studies of intravenous amivantamab demonstrated efficacy across epidermal growth factor receptor (EGFR)–mutated advanced non–small cell lung cancer ( ...

6. rybrevant.com rybrevant.com/

RYBREVANT® (amivantamab-vmjw) RYBREVANT ® is approved to treat advanced non–small cell lung cancer (NSCLC) ... It is not known if RYBREVANT® or LAZCLUZE™ is safe and effective in children.

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.

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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.

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Amivantamab for the Treatment of Patients with Non-Small ... The approval of amivantamab was the first approval of a targeted therapy for patients with advanced NSCLC harboring EGFR exon 20 insertion mutations.

10. clinicaltrials.gov clinicaltrials.gov/study/NCT04599712

NCT04599712 | Pre-Approval Access With Amivantamab ... The purpose of this expanded access program (EAP) is to provide amivantamab for the treatment of participants with metastatic non-small cell lung cancer who ...