Health Canada Green Lights Subcutaneous Atezolizumab for Lung, Breast, and Liver Cancer

Health Canada has approved the use of the subcutaneous formulation of atezolizumab (Tecentriq) for the treatment of patients with lung cancer, breast cancer, or hepatocellular carcinoma (HCC) where the intravenous (IV) formulation has been previously approved.¹

The marketing authorization was supported by data from part 2 of the phase 1b/3 IMscin001 trial (NCT03735121), which showed that subcutaneous atezolizumab administration generated non-inferior levels of the agent in the blood compared with the IV formulation. The study met both of its co-primary end points: trough serum concentration (Ctrough) in cycle 1 and model-predicted area under the curve from days 0 to 21 (AUC0-21 d).

Findings showed the cycle 1 observed Ctrough was 89 μg/mL (coefficient of variation [CV], 43%) for the subcutaneous formulation vs 85 μg/mL (CV, 33%) for IV atezolizumab (geometric mean ratio [GMR], 1.05; 90% CI, 0.88-1.24). The model-predicted AUC0-21 d was 2907 μg d/mL (CV, 32%) for subcutaneous atezolizumab compared with 3328 μg d/mL (CV, 20%) for the IV formulation (GMR, 0.87; 90% CI, 0.83-0.92).²

"While immunotherapy has greatly changed outcomes for many cancer patients, the burden of treatment remains significant. Patients must navigate family, social and financial responsibilities, on top of frequent travel to receive intravenous immune therapy," Sara Moore, MD, a medical oncologist at The Ottawa Hospital, stated in a news release.¹ "This burden can disproportionately affect patients in more rural or remote areas, who can't easily access infusion centers. The availability of subcutaneous treatment options is a great step towards bringing cancer care closer to home."

In January 2024, the European Commission grantedmarketing authorization to subcutaneous atezolizumab co-formulated with Enhanze, a recombinant human hyaluronidase enzyme rHuPH20, for all approved indications of IV atezolizumab. This approval was also supported by data from IMscin001.³

The non-inferiority study enrolled patients at least 18 years of age with histologically or cytologically documented locally advanced or metastatic non–small cell lung cancer who received prior treatment with a platinum-containing regimen or experienced disease recurrence at least 6 months after a prior platinum-based neoadjuvant or adjuvant regimen. Patients also needed to have 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. In part 2, patients also needed to have available tissue and known EGFR status.⁴

Patients were excluded if they had symptomatic, untreated, or actively progressing central nervous system metastases; uncontrolled or symptomatic hypercalcemia; active or history of autoimmune disease or immune deficiency; or a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis.

In part 2, patients were randomly assigned 2:1 to receive subcutaneous atezolizumab at 1875 mg (n = 247) or IV atezolizumab at 1200 mg (n = 124) once every 3 weeks.²

Secondary end points included steady-state exposure, efficacy, safety, and immunogenicity.

Additional data showed that progression-free survival (HR, 1.08; 95% CI, 0.82-1.41), objective response rate (subcutaneous atezolizumab, 12%; IV atezolizumab, 10%), and the incidence of anti-atezolizumab antibodies (19.5%; 13.9%) were similar between both arms.

No new safety signals were reported.

"The adoption of subcutaneous immunotherapy in lung cancer provides tangible benefits for patients and health care providers," Michelle Forman, RN, CON(c), an oncology nurse at Burnaby Hospital Cancer Centre, added in the news release.¹ "For patients, it offers practical benefits like reduced time spent in the clinic, less invasive administration, and greater flexibility with scheduling. It also enables treatment closer to home, reducing travel stress."

References

1. Health Canada authorizes Tecentriq SC (atezolizumab, solution for subcutaneous injection), the first cancer immunotherapy subcutaneous injection, for multiple cancer types. News release. F. Hoffmann-La Roche. April 23, 2024. Accessed April 23, 2024. https://www.biospace.com/article/releases/health-canada-authorizes-tecentriq-and-174-sc-atezolizumab-solution-for-subcutaneous-injection-the-first-cancer-immunotherapy-subcutaneous-injection-for-multiple-cancer-types
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. 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 April 23, 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
4. A study to investigate atezolizumab subcutaneous in patients with previously treated locally advanced or metastatic non-small cell lung cancer. ClinicalTrials.gov. Updated March 25, 2024. Accessed April 23, 2024. https://clinicaltrials.gov/study/NCT03735121