Janssen Pharmaceuticals earned approval for its bispecific antibody, Rybrevant, in locally advanced or metastatic non-small cell lung cancer (NSCLC) harbouring an insertion mutation in exon 20 of the epidermal growth factor receptor (EGFR) gene.
Rybrevant’s antigen binding regions target epitopes on the EGFR and mesenchymal-epithelial transition receptor.
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The approval was based on efficacy data from Janssen’s PAPILLON trial, presented at the European Society for Medical Oncology 2023 event, where patients in the experimental arm of the trial were treated with Rybrevant in combination with carboplatin and pemetrexed and patients in the control arm were treated with carboplatin and pemetrexed alone.
Median progression-free survival (PFS) in the triplet arm of the trial was 11.4 months while it was just 6.7 months in the doublet arm (hazard ratio/HR, 0.40; 95% confidence interval/CI: 0.30-0.53).
The triplet combination also shows a durable response in a subset of patients, as demonstrated by the 18-month PFS rates, where 69% of patients receiving the triplet and 97% of patients receiving the doublet progressed.
Overall survival rates were immature at the most recent 24-month analysis, with 44% of prespecified deaths for the final analysis occurring; however, the trend is moving in favour of the triplet combination (HR, 0.675; 95% CI: 0.42-1.09).
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By GlobalDataThe new combination did not raise any new safety considerations that were inconsistent with the individual drugs; however, rates of grade 3 or higher adverse events (AE) were high, with 75% of the triplet arm experiencing grade 3 or higher adverse events while 54% of the doublet arm did.
The most common treatment-related toxicities in the triplet arm of the trial were neutropenia, paronychia, rash, and anaemia.
This high rate of AEs did not translate into many discontinuations in the triplet arm, with only 7% discontinuing due to high toxicity.
In fact, more than 33% of patients on the doublet arm crossed over to receive Rybrevant once they progressed.
Approximately 10-15% of Caucasian patients and up to 50% of Asian patients with NSCLC harbour a mutation in the EGFR gene, but only 1-10% of those with an EGFR mutation have an insertion mutation in exon 20.
While Rybrevant is likely to become the new standard of care (SOC) in this NSCLC subtype, Janssen is looking for larger targets for its novel bispecific therapy.
This may come from two trials: firstly, the MARIPOSA trial, which compared Rybrevant in combination with Genosco’s lazertinib, a TKI targeting EGFR, against AstraZeneca’s Tagrisso, and secondly, the MARIPOSA II trial, which compared the same Rybrevant-lazertinib combination after progression on Tagrisso (Janssen and Genosco are both owned by Johnson & Johnson).
Positive results were posted for both these trials in the fourth quarter of 2023, and Janssen will be hoping to unseat Tagrisso as the SOC in the wider subtype of EGFR-mutated NSCLC.
Leading data and analytics company GlobalData expects Rybrevant to reach blockbuster status, with the analyst consensus sales forecast for 2030 reaching $3.92bn.
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