Trial results for a Phase 3 study (NCT05388669) investigating a subcutaneous formulation of amivantamab (Rybrevant) in combination with lazertinib for EGFR-mutated advanced or metastatic non-small cell lung cancer were posted on ClinicalTrials.gov on 2026-02-02. The study demonstrated that the subcutaneous formulation achieved higher geometric mean steady-state serum concentrations (Ctrough) and area under the concentration-time curve (AUC) compared to the intravenous formulation.

Background

Amivantamab (Rybrevant) is currently administered intravenously. The purpose of the Phase 3 study (NCT05388669) was to evaluate a new subcutaneous formulation of amivantamab, co-formulated with recombinant human hyaluronidase (SC-CF), to simplify administration and reduce dose times. This new formulation aims to enhance the patient and physician experience by offering easier and accelerated administration for patients with EGFR-mutated advanced or metastatic non-small cell lung cancer.

Trial design

The Phase 3 study (NCT05388669) was designed to compare lazertinib with subcutaneous amivantamab (co-formulated with recombinant human hyaluronidase) against lazertinib with intravenous amivantamab infusion. The trial enrolled 418 participants with advanced or metastatic non-small cell lung cancer. Participants were assigned to either Arm A, receiving lazertinib with amivantamab SC-CF, or Arm B, receiving lazertinib with amivantamab intravenous infusion.

Key results

The trial evaluated the pharmacokinetic profiles of the subcutaneous and intravenous amivantamab formulations. Key measurements included observed serum concentration (Ctrough) of amivantamab at steady state and the Area Under the Concentration (AUC) Time Curve from Day 1 to Day 15 of Cycle 2.

For steady-state Ctrough, the subcutaneous formulation (Arm A) showed higher geometric mean values compared to the intravenous formulation (Arm B). For instance, in regions other than the EU, Arm A reported 206 micrograms per milliliters (mcg/mL) (Geometric Coefficient of Variation: 39.1) versus Arm B's 144 mcg/mL (Geometric Coefficient of Variation: 41.5). Similarly, in the EU and applicable regions, Arm A achieved 335 mcg/mL (Geometric Coefficient of Variation: 32.7) compared to Arm B's 293 mcg/mL (Geometric Coefficient of Variation: 31.7).

Regarding AUC (Day 1-15) of Cycle 2, Arm A demonstrated a geometric mean of 135861 micrograms*hour per milliliters (Geometric Coefficient of Variation: 30.7), slightly higher than Arm B's 131704 micrograms*hour per milliliters (Geometric Coefficient of Variation: 24.0).

A key analysis showed a geometric mean ratio of 1.032 (90.0% CI: 0.976 to 1.09) for Arm B Vs Arm A, indicating the ratio of intravenous to subcutaneous exposure.

What this means

The results indicate that the subcutaneous formulation of amivantamab, when co-administered with lazertinib, achieved higher geometric mean steady-state serum concentrations (Ctrough) and a slightly higher area under the concentration-time curve (AUC) compared to the intravenous formulation. This suggests that the subcutaneous formulation provides at least comparable, and in some metrics, greater systemic exposure to amivantamab. Given the trial's objective to simplify administration and reduce dose times, these pharmacokinetic findings support the potential of the subcutaneous formulation to enhance the treatment experience for patients with EGFR-mutated advanced or metastatic non-small cell lung cancer, while maintaining or improving drug exposure.

Source

The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT05388669, titled "A Study of Lazertinib With Subcutaneous Amivantamab Compared With Intravenous Amivantamab in Participants With Epidermal Growth Factor Receptor (EGFR)-Mutated Advanced or Metastatic Non-small Cell Lung Cancer," were posted on 2026-02-02 on clinicaltrials.gov.