FDA Alert: Subcutaneous Atezolizumab

On September 12, 2024, the US Food and Drug Administration (FDA) approved a subcutaneous coformulation of atezolizumab plus hyaluronidase for patients with non-small cell lung cancer (NSCLC), small cell lung cancer, hepatocellular carcinoma, melanoma, and alveolar soft part sarcoma. This approval was based upon the results of the IMscin001 trial.

IMscin001 was a 2-part, open-label, global, multicenter, phase 1b/3 trial evaluating subcutaneous vs intravenous atezolizumab among previously treated patients with locally advanced or metastatic non-small cell lung cancer. In the phase 1b part 1 of the study determined the dose of subcutaneous atezolizumab that would yield an exposure that is comparable to that of intravenous atezolizumab, finding that “administration of [subcutaneous] atezolizumab appeared to be feasible and well tolerated.”

In part 2 of IMscin001, 371 patients in this population were randomized 2-to-1 to receive either 1875 mg of subcutaneous atezolizumab (n = 247) or 1200 mg intravenous atezolizumab (n = 124) every 3 weeks. This study met both of its co-primary end points, and study authors wrote, when compared to intravenous, subcutaneous atezolizumab “demonstrated noninferior drug exposure level at cycle 1” and “efficacy, safety, and immunogenicity were similar between arms and consistent with the known profile for atezolizumab [intravenous].” They concluded these results “support the use of atezolizumab [subcutaneous] as an alternative to atezolizumab [intravenous].” Updated data reported the median administration time for the subcutaneous injection was 7.1 minutes compared to 40.0 minutes for the intravenous infusion.

IMscin002 was a phase 2, open-label, cross-over study of subcutaneous vs intravenous atezolizumab among patients with PD-L1–positive, resected NSCLC who had previously received chemotherapy and showed no evidence of recurrence (n = 62), and PD-L1 high, stage 4 NSCLC (n = 117). Patients were randomized to receive either 1875 mg subcutaneous atezolizumab or 1200 mg intravenous atezolizumab once every 3 weeks, and after Cycle 3, patients switched the alternative route. After Cycle 6, patients received their preferred route for the continuation period. Patients with resected NSCLC continued treatment for ≤16 cycles while patients with advanced NSCLC continued treatment until clinical benefit, as determined by the investigator. The primary end point in this study was patient preference for subcutaneous vs intravenous atezolizumab at Cycle 6. Key secondary end points were safety and patient-reported outcomes as assessed by a questionnaire.

There were 123 patients who completed the patient preference questionnaire. Most patients (70.7%) preferred subcutaneous atezolizumab vs intravenous atezolizumab (21.1%). There were 8.1% of patients who stated no preference. The main reasons given for preferring the subcutaneous route were reduction of time in clinic (64.4%), feeling more comfortable during administration (46.0%), and less emotional distress (29.9%). After Cycle 6, 79.4% of patients chose subcutaneous atezolizumab for the continuation period. Overall, there were 85.8% of patients who were either very satisfied or satisfied with the subcutaneous route vs 75.2% with the intravenous route. Study authors also noted the subcutaneous route "has the potential for hospital resources to be used more efficiently when local legislation allows out-of-pharmacy preparation.” There were no new safety findings identified, and no safety concerns reported related to switching between treatment routes.

Study authors concluded, “These results support previous findings that atezolizumab [subcutaneous is an equivalent alternative to [intravenous] and has the potential of reducing burden on hospitals and for all patients who are eligible for treatment with atezolizumab, including lung cancer and other approved indications.”

Sources:

Cappuzzo F, Zvirbule Z, Korbenfeld E, et al. Primary results from IMscin002: A study to evaluate patient- and healthcare professional- reported preferences for atezolizumab subcutaneous vs intravenous for the treatment of non-small cell lung cancer. ESMO Open. 2024;9(suppl_3). doi:10.1016/j.esmoop.2024.102706

Cappuzzo F. Primary results from IMscin002: A study to evaluate patient- and healthcare professional- reported preferences for atezolizumab subcutaneous vs intravenous for the treatment of non-small cell lung cancer. Presented at 2024 European Lung Cancer Congress; Match 20-23, 2024. Prague, Czech Republic.

Felip E, Burotto M, Zvirbule Z, et al. Results of a dose-finding phase 1b study of subcutaneous atezolizumab in patients with locally advanced or metastatic non-small cell lung cancer. Clin Pharmacol Drug Dev. Published online March 31, 2021. doi:10.1002/cpdd.936

Burotto M, Zvirbule Z, Mochalova A, et al. IMscin001 Part 2: A randomised phase III, open-label, multicentre study examining the pharmacokinetic, 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.

Burotto M, Zvirbule Z, Alvarez R, et al. Brief report: Updated data from IMscin001 part 2, a randomized phase III study of subcutaneous versus intravenous atezolizumab in patients with locally advanced or metastatic NSCLC. J Thorac Oncol. Published online: May 8, 2024. doi:10.1016/j.jtho.2024.05.005