Amivantamab + Chemotherapy for Non-Small Cell Lung Cancer

(PAPILLON Trial)

Recruiting at 299 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)

308 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to compare the efficacy, as demonstrated by progression-free survival (PFS), in participants treated with amivantamab in combination with chemotherapy, versus chemotherapy alone in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) characterized by EGFR Exon 20ins mutations.

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.

What data supports the effectiveness of the drug Amivantamab combined with chemotherapy for treating non-small cell lung cancer?

Amivantamab, when combined with chemotherapy drugs like carboplatin and pemetrexed, has shown antitumor activity in patients with advanced non-small cell lung cancer (NSCLC) with specific genetic mutations (EGFR exon 20 insertions). This combination has been evaluated in clinical trials, demonstrating its potential effectiveness in treating this type of lung cancer. ^{1 2 3 4 5}

Is the combination of Amivantamab and chemotherapy safe for humans?

Amivantamab combined with chemotherapy has been studied in people with advanced non-small cell lung cancer, and early studies (Phase 1) have shown it to be generally safe. However, more data is needed to fully understand its safety profile. ^{1 2 4 5 6}

What makes the drug Amivantamab combined with chemotherapy unique for treating non-small cell lung cancer?

Amivantamab is unique because it is a bispecific antibody that targets both EGFR and MET, specifically designed for non-small cell lung cancer with EGFR Exon 20 insertion mutations, which are often resistant to other treatments. This combination with chemotherapy offers a novel approach for patients whose cancer has progressed after standard platinum-based chemotherapy. ^{1 2 4 5 7}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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

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]

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]

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]

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 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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

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

2. 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]

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

Pemetrexed in advanced NSCLC: a review of the clinical data. [2015]

4. 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]

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

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

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. New Zealand pubmed.ncbi.nlm.nih.gov

Amivantamab: First Approval. [2021]