Subcutaneous Atezolizumab Approved in Great Britain for All Intravenous Indications

Great Britain’s Medicines and Healthcare Products Regulatory Agency has approved subcutaneous atezolizumab for all indications in which the intravenous formulation of the drug has been approved, including select types of lung, bladder, breast, and liver cancers.

Great Britain’s Medicines and Healthcare Products Regulatory Agency (MHRA) has approved subcutaneous atezolizumab (Tecentriq) for all indications in which the intravenous formulation of the drug has been approved, including select types of lung, bladder, breast, and liver cancers.1

Several prior studies have indicated that most patients with cancer prefer the subcutaneous approach, citing less discomfort and better ease of administration. There is also a shorter duration of treatment with the subcutaneous formulation vs the intravenous approach, cutting administration time from 30 to 60 mins down to approximately 7 minutes.

The regulatory decision is supported by findings from the phase 1b/3 IMscin001 study (NCT03735121), in which comparable levels of the drug were observed in the blood with the subcutaneous vs the intravenous formulation. Additionally, the safety and efficacy profile of subcutaneous atezolizumab proved to be consistent with what had been observed with the intravenous formulation.

“Cancer immunotherapy has transformed the way we treat cancer. Giving [atezolizumab] subcutaneously now offers patients a faster and more flexible treatment option and can free up resources for healthcare systems, while maintaining its established safety profile,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, stated in a press release. “We are working with health authorities globally to bring this option to many more patients around the world.”

The global, multicenter, randomized, phase 1b/3 IMscin001 trial enrolled patients with locally advanced or metastatic non–small cell lung cancer who were naïve to cancer immunotherapy and who experienced failure with platinum-based chemotherapy.2 Patients were required to have measurable disease by RECIST v1.1 criteria and an ECOG performance status ranging from 0 to 1. Those with symptomatic, untreated, or progressive central nervous system metastases were excluded.

Study participants were randomly assigned 2:1 to subcutaneous atezolizumab (n = 247) at 1875 mg every 3 weeks or intravenous atezolizumab (n = 124) at 1200 mg every 3 weeks starting on day 1 of each 21-day cycle. Treatment continued until progressive disease by RECIST v1.1 criteria, loss of clinical benefit, or intolerable toxicity. Notably, crossover was not permitted.

The co-primary pharmacokinetic (PK) end points of the trial included trough serum concentration (Ctrough) and model-predicted area under the curve (SUC) from days 0 to 21 of cycle 1. Secondary PK end points included model-predicted Ctrough at cycle 1, model-predicted Ctrough at steady state, and AUC at steady state.

The median age of patients in the subcutaneous arm was 63.0 years (range, 27-85) vs 66.0 years (range, 42-85) in the intravenous arm, with 45% and 53% of patients, respectively, aged 65 years or older. Most patients, spanning arms, were White (70% vs 60%), had an ECOG performance status of 1 (73% vs 77%), were prior tobacco users (55% vs 52%), and had nonsquamous histology (67% vs 61%).

Most patients in the investigative and control arms had stage IVA disease at diagnosis (37^ vs 42%) and metastatic disease (95% vs 92%). Most patients did not have brain metastases (83% vs 85%) or liver metastases (69% vs 79%). The median number of metastatic sites was 3, with a range of 1 to 8. Moreover, in the subcutaneous arm, 81% of patients received 1 prior therapy, 17% received 2, 2% received 3, and 0% received 4; these rates were 78%, 17%, 4%, and <1%, respectively, in the intravenous arm.

The study met both of its co-primary end points. Ctrough for cycle 1 was 89 mg/mL for the subcutaneous formulation (coefficient of variation [CV], 43%) vs 85 mg/mL (CV, 33%) with the IV formulation; the geometric mean ratio (GMR) was 1.05 (90% CI, 0.88-1.24]). The model-predicted AUC for days 0 to 21 was 2907 mg d/mL (CV, 32%) for the subcutaneous formulation vs 3328 mg d/mL (CV, 20%) for the intravenous formulation; the GMR was 0.87 (90% CI, 0.83- 0.92)].

Additionally, progression-free survival (HR, 1.08 (95% CI 0.82-1.41), objective response rate (12% vs 10%), and incidence of antidrug antibodies (19.5% vs 13.9%) were comparable between the subcutaneous and intravenous arms, respectively. Notably, no new safety concerns were reported, and the Ctrough as well as AUC for days 0 to 21 for the subcutaneous formulation were consistent with what has been reported with the other approved intravenous indications.

“The MHRA regulatory approval is the first for [subcutaneous atezolizumab] worldwide,” according to a press release issued by Roche.1

The marketing authorization seeking the approval of the subcutaneous formulation of atezolizumab in Northern Island is under assessment by the European Medicines Agency. The FDA and other health authorities are also evaluating the formulation as a potential option.

References

  1. Roche’s Tecentriq becomes the first subcutaneous anti-PD-(L)1 cancer immunotherapy available to patients in Great Britain, reducing treatment time to just minutes. News release. F. Hoffmann-La Roche. August 29, 2023. Accessed August 29, 2023. https://www.roche.com/media/releases/med-cor-2023-08-29b
  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