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

(MARIPOSA-2 Trial)

Recruiting at 349 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

776 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination Amivantamab, Lazertinib, and Chemotherapy for Non-Small Cell Lung Cancer?

Research shows that Amivantamab combined with chemotherapy (Carboplatin and Pemetrexed) and sometimes Lazertinib has shown antitumor activity in patients with advanced non-small-cell lung cancer, especially those with specific genetic mutations. This combination has been effective in patients who have not responded to other treatments, like osimertinib. ^{1 2 3 4 5}

Is the combination of Amivantamab, Lazertinib, and Chemotherapy safe for humans?

Amivantamab combined with chemotherapy (carboplatin and pemetrexed) has shown safety in early studies for advanced non-small cell lung cancer, and it is approved for certain types of this cancer. However, more data is needed to fully understand the safety of this combination with lazertinib. ^{1 2 4 6 7}

What makes the drug combination of Amivantamab, Lazertinib, and Chemotherapy unique for treating non-small cell lung cancer?

This drug combination is unique because it targets specific mutations in non-small cell lung cancer (NSCLC) that have become resistant to other treatments, like osimertinib. Amivantamab is a bispecific antibody that targets both EGFR and MET mutations, while Lazertinib is a third-generation EGFR inhibitor that can penetrate the brain, making this combination effective even after other treatments have failed. ^{1 2 3 5 8}

What is the purpose of this trial?

The purpose of this study is to assess the efficacy of adding lazertinib to amivantamab, carboplatin, and pemetrexed (LACP/ACP-L dosing strategies) and amivantamab, carboplatin and pemetrexed (ACP) compared with carboplatin and pemetrexed (CP) in participants with locally advanced or metastatic epidermal growth factor receptor (EGFR) Exon 19del or Exon 21 L858R substitution non-small cell lung cancer (NSCLC) after osimertinib failure. The purpose of the extension cohort is to further describe the safety and efficacy for the ACP-L dosing schedule versus ACP with additional data. After completion of the primary analysis, the study may eventually transition to an open-label extension (OLE) or long-term extension (LTE) phase during which participants will have the option to continue their assigned treatment.

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

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 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, 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]

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]

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 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]

References

1. 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]

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

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

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

Amivantamab plus Lazertinib Is Efficacious in Non-Small Cell Lung Cancer. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

MARIPOSA: phase 3 study of first-line amivantamab + lazertinib versus osimertinib in EGFR-mutant non-small-cell lung cancer. [2022]

6. 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]

7. China 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). [2023]

8. 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]