PAPILLON Study Meets Clinical End Point in Patients With EGFR Exon 20 Insertion–Mutated Advanced NSCLC

The PAPILLON (NCT04538664) phase 3 study of amivantamab-vmjw (Rybrevant) met its primary end point of statistically significant and clinically meaningful improvement in progression-free survival (PFS) in adult patients with newly diagnosed locally advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations whose disease had progressed, when the drug was used in combination with chemotherapy compared with chemotherapy alone, according to a press release issued by Janssen.¹

Amivantamab, an EGFR-MET bispecific antibody, received FDA approval in May 2021 under the agency’s accelerated approval pathway and has also received approval from health authorities in Europe and around the world.

Earlier data from the phase 1/1b CHRYSALIS-2 (NCT04077463) study showed that amivantamab in combination with lazertinib was associated with sustained antitumor activity in patients post osimertinib and chemotherapy naive. Additionally, a safety analysis from the phase 1 PALOMA (NCT04606381) study of a subcutaneous formulation of amivantamab found shorter administration and a marked reduction in the incidence and severity of infusion-related reactions.

"Advanced NSCLC and EGFR-mutated lung cancer has a 5-year survival rate of less than 20%, underscoring an urgent need for more targeted treatment options, especially in earlier lines of therapy," Se-Hoon Lee, MD, PhD, professor of medicine at the Samsung Medical Center and Sungkyunkwan University School of Medicine, and an investigator on the CHRYSALIS study, said in a statement about that trial’s results.² "These long-term data for amivantamab and lazertinib introduce the potential for this combination therapy to be used as first-line treatment for this patient population."

In the PAPILLON study, a safety analysis was consistent with the safety profiles of the individual regimens. Data showed that infusion relation reactions (IRRs) occurred in 66% of the patient safety population treated with amivantamab in the CHRYSALIS study.

Of these patients receiving treatment on week 1 day 1, 65% experienced an IRR, while the incidence of IRRs was 3.4% with the day 2 infusion, 0.4% with the week 2 infusion, and cumulatively 1.1% with subsequent infusions. Of the reported IRRs, 97% were grade 1 to 2, 2.2% were grade 3, and 0.4% were grade 4. The median time to onset was 1 hour (range, 0.1-18 hours) after start of infusion. The incidence of infusion modifications due to IRRs was 62%, and 1.3% of patients permanently discontinued amivantamab due to IRRs.

Additional warnings and precautions include monitoring reactions and considering premedication with antihistamines, antipyretics, and glucocorticoids, as well as monitoring for risk of interstitial lung disease and pneumonitis, dermatologic adverse reactions, ocular toxicity, embryo fetal toxicity, and other adverse reactions.

Other studies of amivantamab being conducted in NSCLC include:

• The phase 3 MARIPOSA (NCT04487080) study assessing amivantamab in combination with lazertinib vs osimertinib and vs lazertinib alone in untreated advanced EGFR-mutated NSCLC.
• The phase 3 MARIPOSA-2 (NCT04988295) study assessing the efficacy of amivantamab (with or without lazertinib) and carboplatin-pemetrexed vs carboplatin-pemetrexed in patients with locally advanced or metastatic EGFR ex19del or exon 21 L858R substitution NSCLC after osimertinib failure.
• The phase 1 CHRYSALIS (NCT02609776) study evaluating amivantamab in participants with advanced NSCLC.
• The phase 2 PALOMA-2 (NCT05498428) study assessing subcutaneous amivantamab in participants with advanced or metastatic solid tumors including EGFR-mutated NSCLC.
• The phase 3 PALOMA-3 (NCT05388669) study assessing lazertinib with subcutaneous amivantamab compared with intravenous amivantamab in participants with EGFR-mutated advanced or metastatic NSCLC.
• The phase 1/2 METalmark (NCT05488314) study assessing amivantamab and capmatinib combination therapy in unresectable metastatic NSCLC.

References

1. The Janssen Pharmaceutical Companies of Johnson & Johnson. Treatment with Rybrevant® (amivantamab-vmjw) plus chemotherapy resulted in statistically significant and clinically meaningful improvement in progression-free survival in patients with newly diagnosed EGFR exon 20 insertion mutation-positive non-small cell lung cancer. News release. PR Newswire. July 17, 2023. Accessed July 17, 2023. https://www.prnewswire.com/news-releases/treatment-with-rybrevant-amivantamab-vmjw-plus-chemotherapy-resulted-in-statistically-significant-and-clinically-meaningful-improvement-in-progression-free-survival-in-patients-with-newly-diagnosed-egfr-exon-20-insertion-mutati-301878443.html

2. Janssen Pharmaceutical Companies of Johnson & Johnson. New long-term data from the CHRYSALIS study show median progression-free survival not reached after 33.6 months of follow-up with first-line use of Rybrevant® (amivantamab-vmjw) and lazertinib combination therapy in patients with treatment-naïve EGFR-mutated advanced non-small cell lung cancer. News release. PR Newswire. June 4, 2023. Accessed July 17, 2023. https://www.prnewswire.com/news-releases/new-long-term-data-from-the-chrysalis-study-show-median-progression-free-survival-not-reached-after-33-6-months-of-follow-up-with-first-line-use-of-rybrevant-amivantamab-vmjw-and-lazertinib-combination-therapy-in-patients-with--301841867.html

This article was updated on August 17, 2023, for clarity and accuracy.