FDA Approves New Subcutaneous Atezolizumab Formulation

Tumor cell being attacked - Generated with Google Gemini AI

• The FDA has approved the subcutaneous formulation of atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza) for all adult indications of the intravenous (IV) version of the agent.
• These include non–small cell lung cancer (NSCLC), small cell lung cancer (SCLC), hepatocellular carcinoma (HCC), melanoma, and alveolar soft part sarcoma (ASPS).
• The approval is supported by the IMscin001 (NCT03735121) trial.

The subcutaneous formulation of atezolizumab has been approved by the FDA for all adult indications of the IV formulation, including in NSCLC, SCLC, HCC, melanoma, and ASPS, offering a more convenient method of administration for the immunotherapy agent.¹

The phase 3 IMscin001 study supported this approval. In the open-label, multicenter, international study, 371 patients with locally advanced or metastatic NSCLC were randomized 2:1 to receive subcutaneous or IV atezolizumab until disease progression or unacceptable toxicity were observed.

The study’s primary end point was atezolizumab exposure, and coprimary pharmacokinetic (PK) end points included of cycle 1_Ctrough and area under the curve (AUC)_0-21days. The geometric mean ratio (GMR; 90% CI) of subcutaneous atezolizumab and IV atezolizumab for cycle 1_Ctrough was 1.05 (range, 0.88-1.24) and AUC_0-21days was 0.87 (range, 0.83-0.92). This met the lower limit of the GMR above the prespecified threshold of 0.8 for comparability.

The overall response rate was 9% (95% CI, 5%-13%) in the subcutaneous arm vs 8% (95% CI, 4%-14%) in the IV arm. There were also no meaningful differences in progression-free survival or overall survival observed between the arms.

The most common adverse reactions of any grade (≥ 10%) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite.

“As the active ingredient of atezolizumab in the [subcutaneous] and IV formulations is identical, it is expected that noninferior systemic exposure would yield a comparable degree of target-site saturation, and thus similar efficacy for both routes of administration. This is supported by the early efficacy and safety findings in this study, showing similar clinical outcomes between treatment arms,” authors wrote in the study published in the Annals of Oncology.

REFERENCES:

1. FDA approves atezolizumab and hyaluronidase-tqjs for subcutaneous injection. News release. FDA. September 12, 2024. Accessed September 12, 2024. https://tinyurl.com/2ku4stnz

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. Published online May 31, 2023. doi:10.1016/j.annonc.2023.05.009