SUMMARY

• There are no systematically collected data to define the post-injection observation time of RYBREVANT FASPRO (amivantamab and hyaluronidase-lpuj) for subcutaneous (SC) use. Clinical judgment should be exercised when considering observation times after RYBREVANT FASPRO injection.
• RYBREVANT FASPRO for SC administration is a coformulation of amivantamab with recombinant human hyaluronidase PH20 (rHuPH20).¹
• LAZCLUZE (lazertinib) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI).²
• PALOMA-3 (NCT05388669) is phase 3, open-label, international, randomized study evaluating the noninferiority of pharmacokinetics, efficacy, and safety of RYBREVANT FASPRO plus LAZCLUZE (n=206) vs RYBREVANT plus LAZCLUZE (n=212) in patients with EGFR-mutated (Exon 19 deletion [Exon19del] or Exon 21 L858R) locally advanced or metastatic non-small cell lung cancer (NSCLC) with disease progression on or after osimertinib and platinum-based chemotherapy (N=418).^1,3
  • Infusion-related reactions (IRRs) cover a range of symptoms or systemic reactions that can occur in response to the infusion or administration of amivantamab, such as chills, dyspnea, chest discomfort, fever, and flushing. In the PALOMA-3 study, where patients were randomized to receive either RYBREVANT FASPRO or RYBREVANT, these reactions were consistently recorded as IRRs to maintain sponsor blinding. IRRs reported in the RYBREVANT FASPRO plus LAZCLUZE treatment group were considered as a systemic reaction related to SC administration.⁴
  • The median time to onset of first IRR (calculated as the time from the most recent amivantamab administration to the start of IRR) in the RYBREVANT FASPRO plus LAZCLUZE treatment group was 105 minutes (range, 0-2056).⁵
• PALOMA-2 (NCT05498428) is an ongoing, phase 2, open-label, international, parallel-cohort study evaluating the efficacy, safety, and pharmacokinetics of first-line RYBREVANT FASPRO with chemotherapy and/or LAZCLUZE combination therapy in patients with locally advanced or metastatic EGFR-mutated NSCLC (N=520).^6,7
  • As amivantamab was administered SC in the PALOMA-2 study, the term administration-related reaction (ARR) is used to describe the systemic reactions associated with SC administration, such as fever, chills, rigors, bronchospasm, headache, rash, pruritus, arthralgia, and hypo- or hypertension.⁸
  • The median onset time for administration-related reactions (ARRs; defined as the start of ARR minus the start of the last injection prior to this event) following RYBREVANT FASPRO injection in patients randomized to RYBREVANT FASPRO plus LAZCLUZE (n=125) was 2.3 hours (range, 0.3-7.2).⁶
• The protocols for the PALOMA-3 and PALOMA-2 studies required patients randomized to the RYBREVANT FASPRO plus LAZCLUZE treatment group to be observed for at least 4 hours after the end of SC administration on Cycle 1 Day 1 only.^9,10

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 09 December 2025. The information included in this response is limited to relevant data from the PALOMA-3 and PALOMA-2 studies.