Janssen-Cilag International NV, a subsidiary of Johnson & Johnson (JNJ), has disclosed findings from the open-label Phase 2 SKIPPirr study. This research aimed to evaluate supplementary prophylactic strategies designed to minimize the incidence of infusion-related reactions (IRRs) in patients with advanced non-small cell lung cancer (NSCLC) carrying epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution mutation, who are treated with intravenous (IV) RYBREVANT (amivantamab).
The company highlighted that the 8 mg pre-medication regimen resulted in an IRR rate of 22.5 percent for intravenous amivantamab, marking a substantial reduction from the historically observed 67.4 percent with standard IRR management.
Monoclonal antibodies are frequently associated with heightened IRR rates, and amivantamab is particularly scrutinized by the European Medicines Agency (EMA) for such reactions.
The study encompassed 40 patients and demonstrated that prophylaxis with 8 mg dexamethasone administered for two days before the initial infusion achieved the primary endpoint—an IRR incidence rate on Cycle 1 Day 1 (C1D1)—with an overall IRR rate of 22.5 percent for IV amivantamab.
Three additional study arms explored alternative prophylactic regimens: Group 1 (dexamethasone 4 mg, taken orally twice daily on the day before treatment), Group 3 (montelukast 10 mg, administered over five days beginning four days before treatment and continuing through the treatment day), and Group 4 (methotrexate 25 mg, delivered via subcutaneous injection between days 7 and 3 before treatment). Groups 1, 3, and 4 were halted due to insufficient efficacy.
The results from Group 2 (dexamethasone 8 mg, administered over two days prior to infusion) revealed a three-fold reduction in IRR incidence compared to standard IRR management for IV amivantamab, against historical data showing a 67.4 percent all-grades incidence rate.
