ASCO 2024 – J&J flies towards a more convenient Rybrevant

Johnson & Johnson reckons its EGFR x cMet bispecific Rybrevant could become a $5bn product, and today the group took a step towards a more convenient version. Data presented at ASCO from the Paloma-3 trial show subcutaneous Rybrevant, plus the oral EGFR-TKI lazertinib, to be equivalent to intravenous Rybrevant plus lazertinib on pharmacokinetic endpoints and overall response rate. 

Unexpectedly, there were also trends towards improvement with the SC version on duration of response, and progression-free and overall survival. Paloma-3 enrolled patients with EGFR Ex19del or L858R-mutated advanced NSCLC who had progressed on Tagrisso and platinum-based chemotherapy.

Paloma-3 data

Notes: *met non-inferiority criteria; **trend in favour of SC. Source: ASCO 2024.

When asked for a potential explanation for the apparently better efficacy with SC Rybrevant, a J&J spokesperson noted that SC absorption via the lymphatic system could enhance Rybrevant’s immune-mediated activity.

There is a precedent for this kind of finding: a SC version of Bristol Myers Squibb’s PD-1 inhibitor Opdivo showed a numerical benefit on ORR and PFS versus IV Opdivo in the Checkmate-67T study.

The safety profile of SC Rybrevant also looked better than IV, with lower incidences of infusion-related reactions and venous thromboembolism.

Filing plans

J&J said during its first-quarter results that it would file the SC version of Rybrevant this year. The group will also present a late-breaking poster at ASCO on Monday on Paloma-2, a study of SC Rybrevant plus lazertinib in first-line EGFR-mutated NSCLC.

When asked which indication(s) the company planed to pursue, J&J told ApexOnco that the studies would support a “broad submission” for SC Rybrevant.

IV Rybrevant plus lazertinib is not yet approved, but could be soon, with a filing of the combo in first-line EGFR-mutant NSCLC submitted last December, based on the Mariposa trial.

However, in the post-Tagrisso setting J&J seems to be focusing on a combo of IV Rybrevant and chemo, based on Mariposa-2.

Rybrevant monotherapy is already marketed for NSCLC with exon 20 insertion mutations, as monotherapy in the second line, and as part of a chemo combo in the first line. This looks like a small niche, and J&J still doesn't split out Rybrevant sales.

A lazertinib combo and a SC Rybrevant formulation could boost revenues, but it looks like the drug has a long way to go to meet the group’s lofty expectations.