PAPILLON represents the first randomized study of newly-diagnosed patients with EGFR exon 20-mutant non–small cell lung cancer to show clinically meaningful results.
Treatment with amivantamab-vmjw (Rybrevant) in combination with the chemotherapy doublet carboplatin and pemetrexed demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in patients with EGFR exon 20 insertion (exon20ins)-mutant non–small cell lung cancer (NSCLC), meeting the primary end point of the phase 2 PAPILLON clinical trial (NCT04538664).1
These results announced by Janssen Pharmaceutical Companies of Johnson & Johnson also showed that the safety profile of amivantamab plus chemotherapy was as expected of each regimen individually. The results from this study will be presented at an upcoming medical meeting, according to Janssen.
PAPILLON is a randomized, open-label, phase 3 study that is investigating the efficacy and safety of amivantamab in combination with chemotherapy in patients with EGFR exon 20 insertion mutated locally advanced or metastatic NSCLC. Patients in the study received intravenous (IV) amivantamab 1400 mg or 17500 mg if above 80 kg in weight. Treatment in the amivantamab arm was administered once weekly up to cycle 2, day 1 followed by 1750 mg on day 1 of each 21-day cycle, beginning with the third cycle. Patients above 80 kg in weight received 2100 mg of treatment instead of 1750 mg. Pemetrexed 500 mg/m2 was given on day 1 of each 31-day cycle, beginning at cycle 3. Finally, IV carboplatin was administered on day 1 of each 31-day cycle for up to 4 cycles. In the chemotherapy alone arm, patients were given matching pemetrexed and carboplatin.2
In addition to PFS, the PAPILLON study is evaluating several secondary end points. The secondary efficacy end points of the study include objective response rate, duration of response, overall survival, time to subsequent therapy, and PFS after first subsequent therapy, The secondary safety end points are the incidence and severity of adverse events, the number of patients with clinical laboratory abnormalities, the number of participants with vital sign abnormalities, serum concentration of amivantamab, the number of patients with anti-amivantamab antibodies, quality-of-life, and patient-reported outcomes.
Patients eligible for inclusion in the study are those with histologically or cytologically confirmed locally advanced or metastatic, nonsquamous NSCLC with an EGFR exon20ins mutation. Patients are required to have measurable disease per RECIST v1.1, an ECOG performance status of 0 or 1, agreement to a tumor biopsy at baseline, as well as periodically. Female patients are also required to have a negative pregnancy test within 72 hours of the first dose of study treatment. Roughly 308 patients who meet these requirements will be enrolled.
Patients excluded from the study are those who appear to have synchronous NSCLC disease, untreated brain metastases, history of spinal cord compression not treated with definitive surgery or radiation, history of interstitial lung disease, and/or, contraindication to the use of the chemotherapy agents used in the study.
"The results from the PAPILLON study support the efficacy of [amivantamab-vmjw] plus chemotherapy in the treatment of patients with non-small cell lung cancer with exon 20 insertion mutations," said Peter Lebowitz, MD, PhD, global therapeutic area head, oncology, Janssen Research & Development, LLC, in a press release.1 "[Amivantamab-vmjw] was the first therapy approved in the relapsed/refractory setting for patients with EGFR exon 20 insertion mutations, a population that continues to experience persistent unmet medical needs. This phase 3 study is the first of several ongoing pivotal programs to read out evaluating [amivantamab-vmjw]-based regimens in patients with EGFR-mutated non-small cell lung cancer."
Amivantamab is an EGFR-MET bispecific antibody that is FDA approved for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon20ins mutations whose disease has progressed on or after platinum-based chemotherapy.
1. 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. The Janssen Pharmaceutical Companies of Johnson & Johnson. July 17, 2023. Accessed July 17, 2023. https://tinyurl.com/4mutjnw8
2. A study of combination amivantamab and carboplatin-pemetrexed therapy, compared with carboplatin-pemetrexed, in participants with advanced or metastatic non-small cell lung cancer characterized by epidermal growth factor receptor (EGFR) exon 20 insertions (PAPILLON). ClincialTrials.gov. Update June 29, 2023. Accessed July 17, 2023. https://clinicaltrials.gov/ct2/show/NCT04538664