Johnson & Johnson submits application to the European Medicines Agency seeking approval of subcutaneous formulation of RYBREVANT▼ (amivantamab) for the treatment of patients with EGFR-mutated non-small cell lung cancer
May 31, 2024 – Clinical Trials, Drug Discovery, Pharmaceutical – ASCO 2024, Janssen, Johnson & Johnson, Johnson & Johnson Innovative Medicine, NSCLC
- Submission is supported by data from the phase 3 PALOMA-3 study featured at the American Society of Clinical Oncology (ASCO) Annual Meeting
- New formulation showed non-inferiority to intravenous administration in fourth positive phase 3 amivantamab study
- Longer overall survival, progression-free survival and duration of response shown with subcutaneous amivantamab; featured in Best of ASCO 2024.
31 May 2024 — Beerse, Belgium — Janssen-Cilag International NV, a Johnson & Johnson company, announced today the submission of an application for the extension of the RYBREVANT▼(amivantamab) marketing authorisation (line extension) to the European Medicines Agency (EMA). This 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, and as a monotherapy in adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations after failure of platinum-based therapy.
The application to the EMA is supported by positive data from the phase 3 PALOMA-3 study (NCT05388669), which demonstrated non-inferior pharmacokinetics and efficacy for SC amivantamab combined with lazertinib compared to intravenous (IV) administration, the currently approved formulation of amivantamab. 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). These late-breaking results, which are the company’s fourth positive phase 3 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 (Abstract #LBA8505) taking place in Chicago, Illinois, US from 31 May – 4 June 2024. This data was also selected for the Best of ASCO 2024 Meetings, which highlight cutting-edge science and reflect leading research in oncology.
“At Johnson & Johnson we constantly strive to transform clinical outcomes for patients and are committed to developing innovative approaches that enhance the treatment experience,” said Henar Hevia PhD, senior director, EMEA Therapeutic Area Lead, Oncology, Johnson & Johnson Innovative Medicine. “The positive data presented at ASCO shows 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 to IV amivantamab, both in combination with lazertinib, in patients with EGFR-mutated advanced or metastatic NSCLC after progression on osimertinib and chemotherapy. Results showed SC amivantamab was non-inferior to IV amivantamab, meeting both co-primary PK endpoints as measured by amivantamab levels in the blood (Ctrough and area under the serum concentration time curve from day 1 to 15).
At a median follow-up of 7 months, the overall response rate was 30% (95% confidence interval [CI], 24–37) in the SC arm and 33% (95% CI, 26–39) for IV (relative risk, 0.92; 95% CI, 0.70–1.23; P=0.001), meeting the non-inferiority criteria. SC amivantamab also demonstrated longer duration of response (DoR), progression-free survival (PFS) and significant improvement in overall survival (OS) compared to IV administration during this time. Specifically, median duration of response was numerically longer for SC amivantamab combined with lazertinib compared to IV (median, 11.2 vs 8.3 months among confirmed responders) as was PFS (median, 6.1 vs 4.3 months; hazard ratio [HR], 0.84; 95% CI, 0.64–1.10; P=0.20). A pre-specified exploratory endpoint showed patients treated with SC amivantamab had significantly longer OS compared with IV (HR, 0.62; 95% CI, 0.42–0.92; nominal P=0.02). 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 is theorised that the efficacy seen with SC amivantamab may be linked to SC absorption, via the lymphatic system, potentially enhancing immune-mediated activity.
“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 NSCLC.”
Of particular note, administration time was substantially shorter for SC amivantamab (median less than approximately five minutes) compared to IV administration (up to five hours), with significantly more patients reporting convenience with the SC administration (85% with SC amivantamab vs 35% with IV administration at end of treatment; P<0.001).
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 to IV were paronychia (54% vs 51%), hypoalbuminemia (47% vs 37%) and rash (46% vs 43%), respectively. The rate of infusion-related reactions for patients treated with SC amivantamab combined with lazertinib was shown to be approximately 5-fold lower than that observed with the IV formulation (13% vs 66%, respectively). No Grade 4 or 5 IRRs were reported. Preventive blood thinning (prophylactic anticoagulation) was used in most patients and was found to be effective in reducing the rate of venous thromboembolic events (VTE). Patients receiving prophylactic anticoagulation had lower rates of VTE (10%) than those without prophylaxis (21%). Furthermore, VTE incidence was numerically lower in the SC arm vs the IV arm (9% vs 14%) regardless of anticoagulation status. Severe bleeding risk was low among patients receiving anticoagulants in the SC (2%) and IV (1%) arms.
“We are always exploring innovative approaches to meet the urgent needs of patients living with EGFR-mutated NSCLC and these compelling findings reinforce the potential for a new route of administration for amivantamab,” said Yusri Elsayed MD MHSc PhD, global therapeutic area head, Oncology, Johnson & Johnson Innovative Medicine. “We look forward to pursuing regulatory submissions for this formulation, as we advance our ambition to transform the first-line treatment of EGFR-mutated NSCLC.”
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