EU's CHMP Recommends Subcutaneous Atezolizumab Approval in Multiple Cancers

The CHMP recommended the approval of subcutaneous atezolizumab for all indications in which intravenous atezolizumab is currently approved; this includes lung, bladder, liver, and breast cancer. The European Commission is anticipated to make a regulatory decision on the approval of subcutaneous atezolizumab in the future.

The European Union’s Committee for Medicinal Products for Human Use (CHMP) has expressed a positive opinion in support of approving subcutaneously administered atezolizumab (Tecentriq) across several disease types, according to a press release from Roche.¹

The CHMP recommended the approval of subcutaneous atezolizumab for all indications in which intravenous atezolizumab is currently approved; this includes lung, bladder, liver, and breast cancer. The European Commission is anticipated to make a regulatory decision on the approval of subcutaneous atezolizumab in the future.

Findings supporting the CHMP’s recommendation came from the phase 1b/3 IMscin001 study (NCT03735121) comparing the pharmacokinetics, efficacy, and safety of subcutaneous and intravenous atezolizumab. The study included 371 patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) that had progressed on previous platinum-based therapy. Previously published data highlighted a median progression-free survival (PFS) of 2.8 months (95% CI, 2.1-3.1) in the subcutaneous atezolizumab arm and 2.9 months (95% CI, 1.7-4.2) in the intravenous arm (HR, 1.08; 95% CI, 0.82-1.41).² Additionally, the objective response rate (ORR) in each respective arm was 12% (95% CI, 8.07%-16.56%) and 10% (95% CI, 5.10%-16.29%). Investigators noted that 19.5% and 13.9% of patients in each respective arm were positive for treatment-emergent anti-atezolizumab antibodies.

Investigators highlighted that rates of adverse effects (AEs), serious AEs, AEs of special interest, and AEs leading to treatment discontinuation were comparable between the intravenous and subcutaneous arms. There were no new safety signals observed in the trial.

“[Atezolizumab] has helped to treat more than 430,000 people diagnosed with some of the most aggressive forms of cancer,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, said in the press release.¹ “Subcutaneous administration offers a faster and more convenient alternative to [intravenous] infusion. The CHMP’s recommendation brings us a step closer to offering the first subcutaneous PD-L1 cancer immunotherapy treatment to patients in the [European Union].”

The IMscin001 study’s primary end points were serum trough concentration (C_trough) of atezolizumab at cycle 1 in part 1 as well as observed serum C_trough and area under the concentration-time curve for up to 21 days in part 2. Secondary end points in part 2 of the trial included ORR, PFS, overall survival, and duration of response.

Patients 18 years and older with cytologically or histologically confirmed locally advanced or metastatic NSCLC, disease recurrence within 6 months after receiving a prior platinum-based adjuvant or neoadjuvant regimen, and measurable disease per RECIST v1.1 criteria were able to enroll on the study. Additional eligibility criteria included having an ECOG performance status of 0 or 1, a life expectancy of at least 12 weeks, and adequate hematologic and end-organ function.

Those with symptomatic or progressive central nervous system metastases or uncontrolled hypercalcemia were unable to enroll on the study. Patients were also unsuitable for enrollment if they had active or prior autoimmune disease, significant cardiovascular disease, or prior allogeneic stem cell or solid organ transplantation.

References

1. 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
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.