ASCO24: J&J's subQ Rybrevant matches efficacy, shrinks infusion time in Phase III trial

2024-05-31

临床结果临床3期优先审批ASCO会议

Johnson & Johnson announced first results from a Phase III study showing that a subcutaneous (SC) form of its lung cancer drug Rybrevant (amivantamab) combined with Leclaza (lazertinib) was non-inferior to the already approved intravenous (IV) version, while delivering substantially faster dosing times and markedly fewer infusion-related reactions.

The PALOMA-3 trial, presented Friday at the American Society of Clinical Oncology (ASCO) annual meeting, is testing the SC formulation of J&J's EGFR/MET-targeting bispecific antibody in 418 patients with EGFR-mutated, advanced or metastatic non-small-cell lung cancer (NSCLC) and exon 19 deletion or L858R mutations, whose disease has progressed on AstraZeneca's Tagrisso (osimertinib) and chemotherapy. Participants were randomised to receive SC or IV Rybrevant, both together with once-daily oral Leclaza, a third-generation EGFR tyrosine kinase inhibitor.

The data were strong enough to prompt the pharma on Friday to submit an application to the European Medicines Agency for the SC Rybrevant-Leclaza combo in the same patient population as PALOMA-3.

Meanwhile, a separate application for IV Rybrevant plus Leclaza is under priority review at the FDA for front-line EGFR-positive NSCLC based on the Phase III MARIPOSA study. The regimen was pitted against Tagrisso, which scored an approval of its own in the first-line setting earlier this year (see – Physician Views Results: Tagrisso use could expand markedly thanks to chemo-combo).

Sign of OS benefit

At the PALOMA-3 presentation Friday, researchers said the overall response rate with SC Rybrevant was 30% after a median 7 months of follow-up, versus 33% for the approved IV version, meeting criteria for noninferiority.

Duration of response appeared to favour SC Rybrevant at 11.2 months versus 8.3 months for the IV form. Over twice as many patients also had responses lasting at least 6 months – at 29% for the SC arm versus 14% for IV. Regarding progression-free survival, the SC and IV forms of Rybrevant showed medians of 6.1 months and 4.3 months, respectively, reflecting a non-significant 16% benefit with the SC version.

In an exploratory analysis, J&J said there was a significant 38% overall survival (OS) benefit with SC Rybrevant. Specifically, 65% of SC patients were alive at the 12-month mark versus 51% with IV. "It is theorised that the efficacy seen with SC [Rybrevant] may be linked to SC absorption via the lymphatic system, potentially enhancing immune-mediated activity," the company stated.

Five minutes to administer

Co-formulated with rHuPH20, Halozyme's ENHANZE drug delivery technology, SC Rybrevant could pave the way for a more pleasant treatment experience for both patients and providers.

With that in mind, a key advantage seen in the study was a substantially reduced administration time for SC Rybrevant – under 5 minutes – compared to up to 5 hours for the current IV formulation. Moreover, infusion-related reactions occurred in just 13% of SC patients versus 66% with IV dosing, about a five-fold decrease. Otherwise, its safety profile largely mirrored its IV counterpart. The most common all-grade adverse events were paronychia, hypoalbuminaemia and rash. No grade 4 or 5 events were reported.

Most patients in the study used prophylactic anticoagulation, which proved to be safe and effective in reducing venous thromboembolic events (VTE). Those on prophylactic anticoagulation had lower VTE rates (10%) compared to those without (21%), although VTE incidence was lower in the SC arm (9%) than in the IV arm (14%), regardless of anticoagulation use. Severe bleeding risk was low and similar in both the SC (2%) and IV (1%) arms.

更多内容，请访问原始网站

文中所述内容并不反映新药情报库及其所属公司任何意见及观点，如有版权侵扰或错误之处，请及时联系我们，我们会在24小时内配合处理。

机构