Source – Johnson & Johnson
The combination of amivantamab-vmjw (Rybrevant) with the chemotherapy doublet carboplatin and pemetrexed has demonstrated a significant improvement in progression-free survival (PFS) for patients with EGFR exon 20-mutant non-small cell lung cancer (NSCLC). These positive results from the Phase II PAPILLON clinical trial (NCT04538664) meet the study’s primary endpoint. Janssen Pharmaceutical Companies of Johnson & Johnson announced these findings and stated that the safety profile of the combination therapy aligns with expectations for each regimen individually. Detailed study results will be presented at an upcoming medical meeting.
The PAPILLON trial is a randomized, open-label, Phase III study investigating the efficacy and safety of amivantamab in combination with chemotherapy for patients with EGFR-mutant locally advanced or metastatic NSCLC. In the trial, patients received intravenous (IV) amivantamab at a dose of 1400 mg or 1750 mg (if body weight exceeded 80 kg). The amivantamab arm received treatment once weekly until cycle 2, day 1, followed by 1750 mg on day 1 of each 21-day cycle starting from the third cycle (patients over 80 kg received 2100 mg instead of 1750 mg). Pemetrexed 500 mg/m2 was administered on day 1 of each 31-day cycle starting from cycle 3, and IV carboplatin was given on day 1 of each 31-day cycle for up to 4 cycles. Patients in the chemotherapy-alone arm received matching pemetrexed and carboplatin.
In addition to evaluating PFS, the PAPILLON study also assesses several secondary endpoints. These include objective response rate, duration of response, overall survival, time to subsequent therapy, and PFS after first subsequent therapy as secondary efficacy endpoints. Secondary safety endpoints include the incidence and severity of adverse events, clinical laboratory abnormalities, vital sign abnormalities, serum concentration of amivantamab, presence of anti-amivantamab antibodies, quality of life, and patient-reported outcomes.
“The results from the PAPILLON study support the efficacy of Rybrevant plus chemotherapy in the treatment of patients with non-small cell lung cancer with exon 20 insertion mutations. Rybrevant 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 RYBREVANT-based regimens in patients with EGFRmutated non-small cell lung cancer.”
– Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC
To be eligible for the study, patients must have histologically or cytologically confirmed locally advanced or metastatic nonsquamous NSCLC with an EGFR exon 20 mutation. They should have measurable disease according to RECIST v1.1 criteria, an ECOG performance status of 0 or 1, agree to a baseline tumor biopsy and periodic biopsies, and female patients must have a negative pregnancy test within 72 hours prior to the first dose of study treatment. The study aims to enroll approximately 308 patients who meet these criteria.
Exclusion criteria include synchronous NSCLC disease, untreated brain metastases, history of spinal cord compression without definitive surgery or radiation, history of interstitial lung disease, and contraindication to the chemotherapy agents used in the study.
