Subcutaneous Atezolizumab Earns European Approval in Several Cancer Indications

Supporting data for the approval came from the phase 1b/3 IMscin001 study (NCT03735121), in which subcutaneously administered atezolizumab demonstrated a comparable efficacy and safety profile compared with intravenous administration among patients with advanced or metastatic non–small cell lung cancer (NSCLC).

The European Commission has approved subcutaneously administered atezolizumab (Tecentriq) co-formulated with the human hyaluronidase enzyme rHuPH20 for the treatment of multiple types of cancer, according to a press release from Halozyme Therapeutics, Inc.¹

The European approval for subcutaneous atezolizumab extends to all prior indications that the intravenous form of the drug was approved for. It is reported that subcutaneous administration of atezolizumab will reduce treatment time to approximately 7 minutes compared with anywhere between 30 and 60 minutes with an intravenous infusion.

“As the first subcutaneous [PD-L1] 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 at Halozyme, said in the press release.¹

Supporting data for the approval came from the phase 1b/3 IMscin001 study (NCT03735121), in which subcutaneously administered atezolizumab demonstrated a comparable efficacy and safety profile compared with intravenous administration among patients with advanced or metastatic non–small cell lung cancer (NSCLC).

Investigators of the study reported a median progression-free survival (PFS) of 2.8 months (95% CI, 2.1-3.1) with subcutaneous atezolizumab compared with 2.9 months (95% CI, 1.7-4.2) in the intravenous arm (HR, 1.08; 95% CI, 0.82-1.41).² The objective response rate (ORR) in each respective arm was 12% (95% CI, 8.07%-16.56%) vs 10% (95% CI, 5.10%-16.29%); all observed responses in both arms were partial responses.

Any-grade adverse effects (AEs) affected 85.8% of patients in the subcutaneous arm compared with 83.9% of those in the intravenous arm. Common AEs in each respective arm included hyperglycemia (2.8% vs 8.1%) and hypercreatinemia (1.2% vs 6.5%). AEs resulting in treatment discontinuation were reported in 1.6% and 3.2% of patients, respectively, and AEs leading to dose interruption occurred among 24.7% and 26.6%.

In the IMscin001 study, patients were randomly assigned 2:1 to receive atezolizumab at 1875 mg once every 3 weeks subcutaneously (n = 247) or at 1200 mg every 3 weeks intravenously (n = 124).

The study’s primary end points included observed C trough serum concentration and model-predicted area under the curve. Secondary end points included ORR, duration of response, overall survival, investigator-assessed PFS, safety, and immunogenicity.

Those with histologically or cytologically confirmed locally advanced or metastatic NSCLC who had not received prior treatment with immunotherapy and progressed following frontline platinum-based therapy were able to enroll on the trial. Additional eligibility criteria included having measurable disease based on RECIST v1.1 criteria and an ECOG performance status of 0 or 1.

The European Union’s Committee for Medicinal Products for Human Use (CHMP) expressed a positive opinion in support of approving subcutaneous atezolizumab in November 2023.³

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, Inc. January 16, 2024. Accessed January 18, 2024. http://tinyurl.com/ycysu8t5
2. 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.
3. Roche’s subcutaneous injection of Tecentriq recommended by the EU’s CHMP for multiple cancer types. News release. Roche. November 14, 2023. Accessed November 28, 2023. https://shorturl.at/eFLNQ