The Papillon Trial was a clinical study for a specific subset of lung cancer patients. It investigated a new combination therapy for individuals with a particular genetic mutation that has historically been difficult to treat. This article will cover the cancer targeted, the treatments tested, the study’s design, and its main outcomes.
The Specific Lung Cancer Targeted
Non-small cell lung cancer (NSCLC) is the most common category of lung cancer, which can be broken down into subtypes based on genetic characteristics. One subtype is defined by mutations in the Epidermal Growth Factor Receptor (EGFR) gene. EGFR is a protein that helps cells grow and divide, but certain mutations can cause it to become overactive, driving cancer growth.
The Papillon Trial focused on a specific and less common mutation known as an EGFR exon 20 insertion. A gene’s exons are the coding instructions for making a protein. An insertion mutation means that extra genetic material has been incorrectly added into exon 20 of the EGFR gene, disrupting the protein’s normal function.
This alteration changes the shape of the part of the EGFR protein where drugs, known as tyrosine kinase inhibitors (TKIs), would normally bind. Standard TKIs effective against more common EGFR mutations often do not work well for cancers with exon 20 insertions. This has made this subtype of NSCLC historically challenging to manage.
Treatments Under Investigation
The clinical trial investigated a combination treatment, comparing it against the existing standard of care. The main drug tested was amivantamab, a bispecific antibody. This means it is engineered to attach to two different targets on cancer cells: the altered EGFR protein and another protein involved in cell growth called MET. This dual-targeting action is designed to shut down multiple cancer-driving signals at once.
The investigational treatment combined amivantamab with standard chemotherapy, specifically the drugs carboplatin and pemetrexed. Chemotherapy agents work by damaging and killing rapidly dividing cells, a hallmark of cancer. The combination was designed to attack the cancer from multiple angles.
The study was structured into two main groups, or “arms,” for a direct comparison. One group of patients received the amivantamab plus chemotherapy regimen. The other group, the control arm, received only the chemotherapy drugs, which represented the standard initial treatment when the trial was designed.
How the Papillon Trial Was Conducted
This study was a Phase 3 clinical trial, a late-stage step in drug development to confirm a treatment’s effectiveness and safety in a large patient population. The results are used to seek approval from regulatory agencies like the U.S. Food and Drug Administration (FDA). The trial enrolled 308 patients with locally advanced or metastatic NSCLC with the EGFR exon 20 insertion mutation who had not received prior treatment.
To ensure a fair comparison, patients were randomly assigned to either the combination therapy group or the chemotherapy-alone group. This process, called randomization, helps to minimize bias by ensuring the groups are as similar as possible. Furthermore, the tumor scans were evaluated by a Blinded Independent Central Review (BICR), meaning the radiologists assessing tumor growth did not know which treatment the patient had received.
The trial’s primary endpoint was to measure Progression-Free Survival (PFS), which is the length of time patients live without their cancer getting worse. The study also looked at several secondary goals, including the Overall Response Rate (ORR), which is the percentage of patients whose tumors shrink, and Overall Survival (OS).
Primary Results and Efficacy
The Papillon Trial met its primary endpoint, demonstrating a clear benefit for the new treatment. Patients who received amivantamab with chemotherapy had a significantly longer Progression-Free Survival (PFS) compared to those who received chemotherapy alone. The median PFS was 11.4 months for the combination group, while it was 6.7 months for the chemotherapy-only group.
This outcome was statistically significant, as shown by a Hazard Ratio (HR) of 0.40. A hazard ratio below 1.0 indicates that the new treatment reduces the risk of an event—in this case, disease progression or death. The result means the amivantamab combination reduced this risk by approximately 60 percent compared to standard chemotherapy.
The positive results extended to secondary endpoints as well. While the data for Overall Survival (OS) were not yet fully mature at the time of the primary analysis, they showed a favorable trend for the amivantamab combination. The findings led to the FDA’s approval of amivantamab plus chemotherapy as a first-line treatment for patients with metastatic NSCLC with EGFR exon 20 insertion mutations.
Safety Profile of the New Regimen
The safety of the amivantamab and chemotherapy combination was also evaluated. While more effective, the new regimen introduced a different set of side effects compared to chemotherapy alone. The most frequently observed adverse events included rash, toxicity affecting the nails, inflammation in the mouth (stomatitis), and infusion-related reactions.
Infusion-related reactions are a known side effect of antibody-based therapies, occurring during or shortly after administration. Other common side effects reported included fatigue, swelling (edema), constipation, and decreased appetite. These effects are consistent with what has been observed in other studies of these drugs.
The overall safety profile was considered manageable within the context of the efficacy benefit. The prescribing information includes specific recommendations for managing these side effects. The addition of amivantamab did not lead to an unexpected level of toxicity that would outweigh its positive impact.