Amivantamab + Lazertinib + Chemotherapy for Non-Small Cell Lung Cancer

(MARIPOSA-2 Trial)

Not currently recruiting at 408 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Must be taking: Osimertinib

Disqualifiers: Brain metastases, Leptomeningeal disease, Cardiovascular disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks for initial cycles, followed by maintenance

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of medications to determine their effectiveness against non-small cell lung cancer (NSCLC) with specific gene mutations (EGFR Exon 19del or Exon 21 L858R). The researchers compare different treatment plans, some incorporating lazertinib (a targeted therapy) with other drugs, to identify the most effective approach after osimertinib, a common treatment, ceases to work. Suitable participants have this type of lung cancer and have not benefited from osimertinib. The study aims to discover if these new combinations can improve treatment outcomes. As a Phase 3 trial, this research represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking osimertinib at least 8 days before starting the study treatment. The protocol does not specify if you need to stop other medications, so it's best to discuss this with the trial team.

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

Research has shown that the combination of amivantamab, lazertinib, carboplatin, and pemetrexed is generally well-tolerated. One study found that 16% of patients experienced eye-related side effects with this combination.

The FDA has already approved amivantamab, when used with carboplatin and pemetrexed, for treating certain types of non-small cell lung cancer (NSCLC) with specific genetic mutations. This approval provides some reassurance about its safety. However, side effects can still occur, so it's important to consider this when deciding to join the trial.

Overall, while the treatment appears to be fairly well-tolerated, discussing potential side effects with a healthcare provider can help in making an informed decision. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for non-small cell lung cancer because they combine innovative therapies with standard chemotherapy to potentially enhance effectiveness. Amivantamab is an antibody that targets specific cancer cell receptors, offering a different approach compared to traditional chemotherapy alone. Lazertinib, a novel EGFR inhibitor, adds another layer by specifically targeting genetic mutations common in lung cancer. These combinations aim to improve outcomes by attacking cancer cells more precisely, potentially leading to better control of the disease with fewer side effects than standard treatments like carboplatin and pemetrexed alone.

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

Research has shown that a combination of amivantamab, lazertinib, carboplatin, and pemetrexed can effectively treat non-small cell lung cancer (NSCLC) with specific EGFR mutations. In this trial, participants in Arm A will receive this combination, which previous studies have found beneficial for patients whose cancer worsened after taking osimertinib. Amivantamab and lazertinib work together to target cancer cells with these mutations, potentially improving disease control. Participants in Arm C will receive amivantamab with carboplatin and pemetrexed, which has proven more effective than standard chemotherapy alone. These findings suggest that adding amivantamab and lazertinib to chemotherapy could enhance treatment for this type of lung cancer. ^{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 non-squamous NSCLC who have an EGFR mutation and whose cancer has worsened after osimertinib treatment. They should be relatively healthy otherwise, with a good performance status (ECOG 0 or 1), and women must test negative for pregnancy. People can't join if they've had certain serious health issues like small cell lung transformation, untreated brain metastases, ILD, significant heart disease, or are at high risk of blood clots without proper anticoagulation.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

My cancer worsened after treatment with osimertinib.

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

Exclusion Criteria

I have brain metastases that are causing symptoms or getting worse.

I have a history of serious heart or blood clot issues.

I received radiotherapy for lung cancer relief less than 2 weeks ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Lazertinib, Amivantamab, Pemetrexed, and Carboplatin for 4 cycles, followed by maintenance therapy until disease progression

12 weeks for initial cycles, followed by maintenance

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 1 year 7 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

up to 4 years 10 months

What Are the Treatments Tested in This Trial?

Interventions

• Amivantamab
• Carboplatin
• Lazertinib
• Pemetrexed

Trial Overview

The study tests the effectiveness of combining Amivantamab and Lazertinib with platinum-based chemotherapy (Carboplatin/Pemetrexed) against just the chemotherapy in patients whose NSCLC has progressed post-Osimertinib therapy. It aims to see if adding these targeted therapies improves outcomes.

How Is the Trial Designed?

Group I: Arm C: ACP (Amivantamab, Carboplatin and Pemetrexed) Experimental Treatment 3 Interventions

Participants will receive Amivantamab, Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab and Pemetrexed as maintenance until disease progression.

Group II: Arm C2 (Extension Cohort): ACP Experimental Treatment 3 Interventions

Participants will receive Amivantamab, Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab and Pemetrexed as maintenance until disease progression.

Group III: Arm A: LACP/ACP-L Experimental Treatment 4 Interventions

LACP dosing (study start until 6 November 2022): Participants will receive Lazertinib orally along with Amivantamab, Pemetrexed, and Carboplatin as IV infusion starting on Cycle 1 Day 1 for 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression. ACP-L dosing (from 7 November 2022 until study completion): Participants will receive Amivantamab, Pemetrexed, and Carboplatin starting on Cycle 1 Day 1 for 4 cycles. Lazertinib in ACP-L will start on Cycle 5 Day 1 or sooner if carboplatin is discontinued before cycle 4 (each cycle consists of 21 days). Beginning with Cycle 5 Day 1, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression.

Group IV: Arm A2 (Extension Cohort): ACP-L Experimental Treatment 4 Interventions

Participants will receive Amivantamab, Pemetrexed and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days), Lazertinib will start on C5D1 or sooner if carboplatin is discontinued earlier). After 4 cycles, participants will receive Pemetrexed, Amivantamab, Lazertinib as maintenance until disease progression.

Group V: Arm B: CP (Carboplatin and Pemetrexed) Active Control 2 Interventions

Participants will receive Pemetrexed in combination with Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Pemetrexed as maintenance until disease progression.

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]

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]

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). Renaud, E., Ricordel, C., Corre, R., 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]

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-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]

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