A Phase 3 study evaluating a subcutaneous formulation of amivantamab for advanced or metastatic non-small cell lung cancer (NSCLC) reached primary completion on 2024-01-03. The trial compared the subcutaneous formulation with intravenous amivantamab, demonstrating that the subcutaneous form achieved comparable systemic exposure, with a geometric mean ratio for AUC of 1.032 (90% CI: 0.976, 1.09).
Background
The study investigated a new subcutaneous formulation of amivantamab, co-formulated with recombinant human hyaluronidase (SC-CF), in combination with lazertinib. Amivantamab (Rybrevant) is currently administered intravenously for advanced or metastatic non-small cell lung cancer (NSCLC). The primary objective of developing the subcutaneous formulation is to simplify administration and reduce dose times, aiming to enhance the patient and physician experience.
Trial design
The Phase 3 study (NCT05388669) enrolled 418 participants with advanced or metastatic non-small cell lung cancer. The trial compared a subcutaneous formulation of amivantamab, co-formulated with recombinant human hyaluronidase (SC-CF), administered alongside lazertinib (Arm A) against intravenous amivantamab with lazertinib (Arm B). The study aimed to assess the new subcutaneous formulation for its potential to simplify administration and reduce dose times.
Key results
The trial reported pharmacokinetic data comparing the subcutaneous and intravenous formulations of amivantamab:
- For regions outside the EU, steady-state Ctrough for subcutaneous amivantamab (Arm A) was a geometric mean of 206 micrograms per milliliters (mcg/mL) (Geometric Coefficient of Variation [GCV]: 39.1%) versus 144 mcg/mL (GCV: 41.5%) for intravenous (Arm B).
- For EU regions, Ctrough for subcutaneous amivantamab (Arm A) was a geometric mean of 335 mcg/mL (GCV: 32.7%) versus 293 mcg/mL (GCV: 31.7%) for intravenous (Arm B).
- The Area Under the Concentration (AUC) Time Curve (Day 1-15 of Cycle 2) for subcutaneous amivantamab (Arm A) was a geometric mean of 135861 micrograms*hour per milliliters (GCV: 30.7%) versus 131704 micrograms*hour per milliliters (GCV: 24.0%) for intravenous (Arm B).
Key analyses included:
- A geometric mean ratio for AUC (Arm B Vs Arm A) of 1.032, with a 90.0% confidence interval of 0.976 to 1.09.
- Cox regression model parameters of 1.427 (90.0% CI: 1.266, 1.61) and 1.145 (90.0% CI: 1.04, 1.261) for Arm B Vs Arm A were also reported.
What this means
The pharmacokinetic results from this Phase 3 study indicate that the subcutaneous formulation of amivantamab provides comparable, and in some measures, higher systemic exposure compared to the intravenous formulation. Specifically, the geometric mean ratio for AUC of 1.032 (90% CI: 0.976, 1.09) suggests that the subcutaneous formulation is bioequivalent to the intravenous form. The higher Ctrough values observed with the subcutaneous formulation in both reported regions further support its potential efficacy. These findings align with the trial's objective to simplify administration and reduce dose times, potentially offering a more convenient treatment option for patients with advanced or metastatic non-small cell lung cancer while maintaining or improving drug exposure.
Source
The information regarding the primary completion of this trial and its results was obtained from ClinicalTrials.gov, a public database of clinical studies. The data 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", was posted on 2024-01-03 on clinicaltrials.gov.