Janssen-Cilag International NV, a Johnson & Johnson company, has submitted an application for the extension of Rybrevant’s (amivantamab) marketing authorisation to the European Medicines Agency (EMA).
The application seeks approval for the use of a subcutaneous (SC) formulation of amivantamab in combination with lazertinib for the first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletion or L858R mutations.
It also endeavours to get Rybrevant approved as a monotherapy in adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations after failure of platinum-based therapy.
PALOMA-3 highlights Rybrevant’s efficacy
The application to the EMA is supported by positive data from the Phase III PALOMA-3 study (NCT05388669), which demonstrated non-inferior pharmacokinetics and efficacy for SC amivantamab combined with lazertinib compared with intravenous (IV) administration, the currently approved formulation of amivantamab.1
Administration time for SC amivantamab was reduced to approximately five minutes from five hours for the first IV amivantamab infusion (across two days) and showed a five-fold reduction in infusion-related reactions (IRRs).1
These late-breaking results, which are the company’s fourth positive Phase III readout for the amivantamab clinical programme, were featured for the first time as an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.
Henar Hevia, Senior Director, EMEA Therapeutic Area Lead, Oncology, Johnson & Johnson Innovative Medicine, commented: “The positive data presented at ASCO show the potential for improved safety outcomes and added convenience for patients treated with the subcutaneous formulation of amivantamab, and we now look forward to working with the EMA to provide this option to patients who may benefit from it, as soon as possible.”
The PALOMA-3 study evaluated the pharmacokinetics (PK), efficacy and safety of SC amivantamab (administered via manual injection) compared with IV amivantamab, both in combination with lazertinib, in patients with EGFR-mutated advanced or metastatic NSCLC after progression on osimertinib and chemotherapy.1
Subcutaneous amivantamab met its primary endpoints
Results showed SC amivantamab was non-inferior to IV amivantamab, meeting both co-primary PK endpoints as measured by amivantamab levels in the blood.
At a median follow-up of seven months, the overall response rate was 30% in the SC arm and 33% for IV, meeting the non-inferiority criteria.1
SC amivantamab also demonstrated longer duration of response (DoR), progression-free survival (PFS) and significant improvement in overall survival (OS) compared with IV administration during this time.1
Specifically, median duration of response was numerically longer for SC amivantamab combined with lazertinib compared with IV — as was PFS.
Improving OS through subcutaneous administration
A pre-specified exploratory endpoint showed patients treated with SC amivantamab had significantly longer OS compared with IV.
At 12 months, 65% of patients who received SC amivantamab combined with lazertinib were alive compared with 51% of those treated with the IV regimen.
It's theorised that the efficacy seen with SC amivantamab may be linked to SC absorption, via the lymphatic system, potentially enhancing immune-mediated activity.1
“The PALOMA-3 data show that subcutaneous amivantamab offers shorter infusion times and lower rates of administration-related reactions with pharmacokinetics and efficacy comparable to the current IV administration,” said Dr Natasha B. Leighl, medical oncologist at the Princess Margaret Cancer Centre in Toronto, Canada, and the presenting author. “I look forward to seeing how these findings can make a meaningful difference in clinical practice by potentially improving the treatment experience for patients with EGFR-mutated non-small cell lung cancer.”
Amivantamab’s safety profile
The overall safety profile of SC amivantamab is consistent with the known profile of IV administration.
The most common all-Grade adverse events (≥ 20%) for SC amivantamab compared with IV were paronychia (54% vs 51%), hypoalbuminemia (47% vs 37%) and rash (46% vs 43%), respectively.1
The rate of infusion-related reactions for patients treated with SC amivantamab combined with lazertinib was shown to be approximately five-fold lower than that observed with the IV formulation (13% vs 66%, respectively).1