Amivantamab + Chemotherapy for Non-Small Cell Lung Cancer

(PAPILLON Trial)

Not currently recruiting at 374 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Must not be taking: Corticosteroids

Disqualifiers: Brain metastases, Spinal cord compression, ILD, 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: 21

Duration: 12 weeks (4 cycles of 21 days each)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with a specific type of advanced lung cancer called non-small cell lung cancer (NSCLC) that has a rare mutation known as EGFR Exon 20ins. The study aims to determine if adding amivantamab (a monoclonal antibody) to standard chemotherapy is more effective in slowing the cancer than chemotherapy alone. Participants diagnosed with this type of NSCLC and possessing this specific mutation might be suitable for the trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether 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 using amivantamab with chemotherapy is approved for treating certain types of non-small cell lung cancer (NSCLC), particularly in patients with changes in the EGFR gene. This approval indicates its safety for individuals with this condition.

In earlier studies, patients who received amivantamab with chemotherapy experienced good safety outcomes. Most did not encounter serious side effects, indicating the treatment was generally well-tolerated.

Amivantamab alone is also approved for treating advanced NSCLC, further supporting its safety in humans.

Overall, while all treatments can have some side effects, the approval and research findings suggest that amivantamab with chemotherapy is generally safe for treating NSCLC. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for non-small cell lung cancer?

Researchers are excited about amivantamab added to chemotherapy for non-small cell lung cancer because it offers a novel approach compared to the standard options like pembrolizumab, nivolumab, or chemotherapy alone. Amivantamab is an antibody that specifically targets and blocks the activity of EGFR and MET proteins, which are often involved in cancer cell growth and survival. This dual-targeting mechanism could potentially lead to more effective tumor control and improved outcomes for patients. Meanwhile, chemotherapy remains a powerful tool by directly killing rapidly dividing cancer cells, and when used together with amivantamab, it may enhance overall treatment efficacy.

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

Research has shown that amivantamab, when combined with chemotherapy, is more effective for treating advanced non-small cell lung cancer (NSCLC) with certain EGFR mutations. In this trial, participants in one arm will receive the combination of amivantamab and chemotherapy, which studies have found leads to better results than chemotherapy alone. This includes longer periods where the cancer does not worsen, known as progression-free survival. Amivantamab targets EGFR and MET proteins, which aid cancer cell growth. It is specifically approved for NSCLC with EGFR exon 20 insertions, providing a focused treatment for this mutation. Overall, evidence supports amivantamab's potential to improve treatment outcomes for patients with these genetic markers. ^{2 6 7 8 9}

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-small cell lung cancer (NSCLC) that has a specific mutation called EGFR Exon 20 insertion. They must have measurable disease, be in good physical condition (ECOG status 0 or 1), and agree to genetic tests of their tumor. Women who can have children must test negative for pregnancy.

Inclusion Criteria

I am a woman who can have children, have tested negative for pregnancy, and agree to ongoing pregnancy tests.

I agree to let doctors test my tumor and blood for genetic research.

My lung cancer is advanced, not squamous, and has a specific EGFR mutation.

Exclusion Criteria

I have untreated spinal cord compression.

I have a history of lung conditions like ILD or radiation pneumonitis.

I cannot take carboplatin or pemetrexed due to health reasons.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive amivantamab in combination with chemotherapy or chemotherapy alone for up to 4 cycles, followed by maintenance therapy until disease progression

12 weeks (4 cycles of 21 days each)

Weekly visits for amivantamab, every 21 days for chemotherapy

Open-label extension (OLE)

Participants continue to receive the study treatment or cross over to amivantamab in the OLE phase

Until disease progression

Long-term extension (LTE)

Participants who completed the OLE period continue to receive the same treatment

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 29 months

What Are the Treatments Tested in This Trial?

Interventions

• Amivantamab
• Carboplatin
• Pemetrexed

Trial Overview

The study is testing the effectiveness of Amivantamab combined with Carboplatin-Pemetrexed chemotherapy versus just the chemotherapy alone. The main goal is to see which treatment stops the cancer from progressing longer.

How Is the Trial Designed?

Group I: Arm B: Chemotherapy Alone Experimental Treatment 2 Interventions

Participants will receive pemetrexed 500 mg/m\^2 IV infusion (with vitamin supplementation) on Day 1 of each 21-day cycle, in combination with carboplatin for up to 4 cycles, and then as maintenance monotherapy until disease progression. Carboplatin AUC 5 IV infusion will be administered on Day 1 of each 21-day cycle for up to 4 cycles. Following the primary analysis for efficacy, the study will transition to an OLE phase and participants will either continue to receive the chemotherapy or cross over to amivantamab in OLE phase. Participants who completed OLE period will enter LTE period and continue to receive same treatment.

Group II: Arm A: Amivantamab + Chemotherapy Experimental Treatment 3 Interventions

Participants will receive pemetrexed 500 milligram per meter square (mg/m\^2) intravenous (IV) infusion (with vitamin supplementation) on Day 1 of each 21-day cycle, in combination with carboplatin for up to 4 cycles, and then as maintenance monotherapy until disease progression. Carboplatin area under the concentration-time curve 5 milligram per milliliter (mg/mL) per minute (AUC 5) will be administered as IV infusion on Day 1 of each 21 day cycle, for up to 4 cycles. Participants will receive amivantamab 1400 mg (1750 mg if body weight is \>=80 kilogram \[kg\]) by IV infusion once weekly up to Cycle 2 Day 1, then 1750 mg (2100 mg if body weight is \>=80 kg) on Day 1 of each 21-day cycle, starting with Cycle 3. Following the primary analysis for efficacy, the study will transition to an OLE phase and participants will continue to receive the amivantamab plus chemotherapy in OLE phase. Participants who completed OLE period will enter LTE period and continue to receive same treatment.

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

Pemetrexed (Alimta) is an effective treatment for mesothelioma and shows comparable survival rates to docetaxel in advanced non-small-cell lung cancer (NSCLC) while causing significantly fewer and less severe side effects.

In combination with platinum agents, pemetrexed has demonstrated significant activity and a favorable toxicity profile, making it a promising option for treating thoracic malignancies and warranting further research with other novel drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed in advanced NSCLC: a review of the clinical data. Zinner, RG., Fossella, FV., Herbst, RS.[2015]

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 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 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 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]

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]

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]

Citations

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Chinese patients with EGFR exon20ins under SACT had poor clinical outcomes comparing to those with common EGFR mutations in the study.

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RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE™ ...

Median overall survival not yet reached with projected improvement of more than one year versus osimertinib.

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sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0169500225006580

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ascopubs.org

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6.

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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.

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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 ...

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RYBREVANT® (amivantamab-vmjw) in Combination With ...

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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.