European Commission Approves Subcutaneous Atezolizumab With Enhanze for Several Cancers

The European Commission granted marketing authorization for SC atezolizumab co-formulated with Enhanze for all approved indications of IV atezolizumab.

The European Commission has granted marketing authorization for subcutaneous atezolizumab (Tecentriq) co-formulated with Enhanze, a recombinant human hyaluronidase enzyme rHuPH20, for all approved indications of intravenous (IV) atezolizumab. The represents the first PD-(L)1 cancer immunotherapy for subcutaneous injection approved in the European Union.1

The decision was announced following the read out of data from the pivotal phase 1b/3 IMscin001 trial (NCT03735121),2 which demonstrated comparable levels of subcutaneous atezolizumab in the blood and a similar safety and efficacy profile to that of the IV formulation.

“As the first subcutaneous PD-(L)1 cancer immunotherapy in Europe, [subcutaneous atezolizumab] can provide a new treatment option that can enhance the treatment experience for patients and caregivers while freeing up resources in constrained health care systems,” Helen Torley, MB, ChB, MRCP, president and chief executive officer of Halozyme, stated in a news release.1

Traditional IV infusion can take between 30 and 60 minutes compared with subcutaneous infusion, which markedly reduces treatment time to approximately 7 minutes. Moreover, when delivered subcutaneously, atezolizumab can be administered by a health care professional outside of the hospital, in a community care setting, or at home, according to national regulations and health systems.

In the pivotal trial, 90% of health care professionals stated that the subcutaneous formulation is easy to administer and 75% said that it could save time for health care teams compared with the IV formulation.

To be eligible for enrollment, patients had to have histologically or cytologically confirmed locally advanced or metastatic NSCLC; exposure to prior platinum-containing therapy or disease recurrence within 6 months of receiving prior platinum-based therapy in the adjuvant or neoadjuvant setting; measurable disease per RECIST v1.1 criteria; an ECOG performance status of 0 or 1; a life expectancy of at least 12 weeks; and adequate hematologic and end-organ function.2

In the randomized phase 3 portion of the open-label, multicenter, noninferiority trial, patients with locally advanced or metastatic non–small cell lung cancer were randomly assigned 2:1 to receive 1875 mg of subcutaneous atezolizumab (n = 247)––the recommended dose confirmed in the earlier phase 1b portion of the trial––or 1200 mg of IV atezolizumab (n = 124) every 3 weeks. The co-primary end points were cycle 1 trough serum concentration (Ctrough) and model-predicted area under the curve from day 0 to 21 (AUC0-21). Secondary end points were steady-state exposure, efficacy, safety, and immunogenicity.3

Results showed that the study met both of its co-primary end points. The cycle 1 observed Ctrough for serum concentrations for subcutaneous and IV atezolizumab were 89 μg/mL (coefficient of variation [CV], 43%) and 85 μg/ml (CV, 33%), respectively (geometric mean ratio [GMR], 1.05; 90% CI, 0.88-1.24). Moreover, the model-predicted AUC0-21 was 2907 μg d/mL (CV, 32%) for subcutaneous atezolizumab vs 3328 μg d/mL (CV, 20%) for IV atezolizumab (GMR, 0.87; 90% CI, 0.83-0.92).

Regarding efficacy, similar progression-free survival (HR, 1.08; 95% CI, 0.82-1.41), objective response rate (subcutaneous, 12% vs IV, 10%), and incidence of anti-atezolizumab antibodies (subcutaneous, 19.5% vs IV, 13.9%) were observed between arms.

No new safety concerns were identified.

References

  1. Halozyme announces Roche receives European Commission approval of Tecentriq SC with ENHANZE representing the EU’s first subcutaneous PD-(L)1 cancer immunotherapy for multiple cancer types. News release. Halozyme Therapeutics. January 16, 2024. Accessed January 16, 2024. https://www.prnewswire.com/news-releases/halozyme-announces-roche-receives-european-commission-approval-of-tecentriq-sc-with-enhanze-representing-the-eus-first-subcutaneous-pd-l1-cancer-immunotherapy-for-multiple-cancer-types-302035190.html
  2. A study to investigate atezolizumab subcutaneous in patients with previously treated locally advanced or metastatic non-small cell lung cancer. ClinicalTrials.gov. Updated December 22, 2023. Accessed January 16, 2024. https://clinicaltrials.gov/study/NCT03735121
  3. Burotto M, Zvirbule Z, Mochalova A, et al. IMscin001 Part 2: a randomised phase III, open-label, multicentre study examining the pharmacokinetics, efficacy, immunogenicity, and safety of atezolizumab subcutaneous versus intravenous administration in previously treated locally advanced or metastatic non-small-cell lung cancer and pharmacokinetics comparison with other approved indications. Ann Oncol. 2023;34(8):693-702. doi:10.1016/j.annonc.2023.05.009