CHMP Supports Approval of Subcutaneous Atezolizumab for All Current IV Indications

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of subcutaneous atezolizumab (Tecentriq) for all indications in which the intravenous (IV) formulation is approved, including certain types of lung, liver, bladder, and breast cancer. The European Commission is expected to make its final decision on the approval soon.¹

The CHMP’s positive opinion is based on pivotal data from the phase 1b/3 IMscin001 trial (NCT03735121), which showed similar levels of atezolizumab in the blood when administered subcutaneously, as well as a comparable safety and efficacy profile vs the IV formulation.^1,4

“[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, stated in a news release.¹ “Subcutaneous administration offers a faster and more convenient alternative to IV 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 global, multicenter, randomized IMscin001 trial is evaluating the pharmacokinetics, safety, and efficacy of subcutaneous atezolizumab compared with IV atezolizumab in immunotherapy-naive patients with locally advanced or metastatic non–small cell lung cancer for whom prior platinum-based therapy has failed (n = 371).1,2 Patients were randomly assigned 2:1 to receive 1875 mg of subcutaneous atezolizumab (n = 247) or 1200 mg of IV atezolizumab (n = 124) every 3 weeks.³

Previous findings from the trial demonstrated that the study had met its co-primary end points, demonstrating non-inferior drug exposure for cycle 1 observed trough serum concentrations (C_trough) and model-predicted area under the curve for days 0 to 21 between the subcutaneous and IV formulations.³

Updated results from the study, which were presented at the 2023 ESMO Congress, showed that at a median follow-up of 9.5 months, subcutaneous atezolizumab continued to demonstrate equivalence for key secondary end points including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) vs IV treatment.³

The results demonstrated that the median OS was 10.7 months (95% CI, 8.5-13.8) with the subcutaneous formulation vs 10.1 months (95% CI, 7.5-12.1) with the IV formulation (HR, 0.88; 95% CI, 0.67-1.16). Median PFS was 2.8 months (95% CI, 2.7-4.1) with subcutaneous atezolizumab vs 2.9 months (95% CI, 1.8-4.2) with IV atezolizumab (HR, 1.05; 95% CI, 0.83-1.33). The confirmed ORRs were 11.0% (95% CI, 7.4%-15.6%) and 10.5% (95% CI, 5.7%-17.3%), respectively. All responses were partial responses.

Median duration of response was 15.1 months (95% CI, 5.6–not evaluable [NE]) with the subcutaneous formulation vs 11.2 months (95% CI, 4.2-NE) with the IV formulation (delta, 0.54; 95% CI, –6.56 to 7.63).

Moreover, median administration time was significantly reduced with subcutaneous administration at 7.1 minutes (95% CI, 6.6-7.4) vs 40.0 minutes (95% CI, 37.5-45.0) with IV administration.

Regarding safety, any-grade adverse effects in the subcutaneous and IV arms, respectively, included anemia (19% vs 17%), dyspnea (11% vs 15%), and fatigue (12% vs 13%). Grade 3/4 AEs were less common in the subcutaneous arm compared with the IV arm (21% vs 31%), as were serious AEs (19% vs 27%). However, 6% of patients in both arms experienced a fatal AE. AEs of special interest occurred in both arms: hepatitis (12% vs 14%), hypothyroidism (11% vs 7%), and rash (9% vs 11%). AEs leading to dose discontinuation occurred in 4% vs 7% of patients in the subcutaneous and IV arms, respectively.

As part of the study, patient-reported outcomes (PROs) were collected on day 1 of the first 6 cycles of therapy and then every second cycle until treatment discontinuation. Health-care providers were also asked to complete questionnaires on subcutaneous and IV administration after giving at least 3 doses of each formulation.

Results showed that mean PRO scores for each arm fell within 10% of each other for global health status, role and physical functioning, and satisfaction with therapy. Moreover, 90% of health-care professionals who were surveyed as part of the study agreed that giving the subcutaneous formulation was fairly easy/very easy; 85% were satisfied/very satisfied; and 75% reported that subcutaneous administration could save time compared with the IV formulation.

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 14, 2023. https://www.roche.com/media/releases/med-cor-2023-11-14
2. A study to investigate atezolizumab subcutaneous in patients with previously treated locally advanced or metastatic non-small cell lung cancer. ClinicalTrials.gov. Updated October 4, 2023. Accessed November 14, 2023. https://clinicaltrials.gov/study/NCT03735121
3. Burotto M, Zvirbule Z, Alvarez R, et al. IMscin001 part 2 updated results: efficacy, safety, immunogenicity and patient-reported outcomes (PROs) from the randomised phase III study of atezolizumab (atezo) subcutaneous (SC) vs intravenous (IV) in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). Ann Oncol. 2023;34(suppl 2):S823. doi:10.1016/j.annonc.2023.09.2478
4. 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