FDA Approves Subcutaneous Atezolizumab (Tecentriq Hybreza) for Multiple Cancer Types
核心洞察
The FDA has approved a subcutaneous formulation of atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza) for all indications of intravenous atezolizumab.
This includes non-small cell lung cancer (搜索), small cell lung cancer (搜索), hepatocellular carcinoma (搜索), melanoma (搜索), and alveolar soft part sarcoma (搜索).
The approval was based on the IMscin001 trial, which demonstrated comparable drug levels and similar safety and efficacy profiles to IV administration.
The FDA has approved atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza) for subcutaneous injection, covering all adult indications previously approved for the intravenous formulation of atezolizumab (Tecentriq). This includes non-small cell lung cancer (搜索) (NSCLC), small cell lung cancer (搜索) (SCLC), hepatocellular carcinoma (搜索) (HCC), melanoma (搜索), and alveolar soft part sarcoma (搜索) (ASPS).
The approval is based on data from the phase 3 IMscin001 trial (NCT03735121), a randomized, open-label, multicenter study. The trial evaluated the pharmacokinetics, efficacy, immunogenicity, and safety of subcutaneous versus intravenous administration of atezolizumab in patients with previously treated locally advanced or metastatic NSCLC who were naive to cancer immunotherapy and who had disease progression after platinum-based chemotherapy. A total of 371 patients were randomized 2:1 to receive either subcutaneous atezolizumab and hyaluronidase-tqjs or intravenous atezolizumab until disease progression or unacceptable toxicity.
The study's primary endpoint was atezolizumab exposure, with co-primary pharmacokinetic endpoints of cycle 1 Ctrough and area under the curve (AUC) from 0 to 21 days. The geometric mean ratio (GMR) of subcutaneous to intravenous atezolizumab for cycle 1 Ctrough was 1.05 (90% CI, 0.88-1.24), and the AUC0-21days was 0.87 (90% CI, 0.83-0.92), meeting the pre-specified comparability threshold.
Efficacy and Safety
Efficacy endpoints including overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were similar between the subcutaneous and intravenous formulations. The confirmed ORR was 9% (95% CI: 5%-13%) in the subcutaneous arm and 8% (95% CI: 4%-14%) in the intravenous arm.
The most common adverse reactions (≥ 10%) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite. No new safety signals were identified with the subcutaneous formulation.
Dosing and Administration
The recommended dosage is a 15 mL injection (containing 1875 mg of atezolizumab and 30,000 units of hyaluronidase) administered subcutaneously in the thigh over approximately 7 minutes every 3 weeks. This compares favorably to the 30-60 minutes required for intravenous infusions, offering a more convenient option for patients.
Patient Preference
Phase 2 data from the IMscin002 study indicated that 71% of patients preferred the subcutaneous formulation over intravenous administration, citing increased comfort, reduced emotional stress, and less time spent in the clinic. After experiencing both formulations, 79% of patients chose the subcutaneous option.
Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Genentech, stated that the subcutaneous formulation offers patients and physicians greater flexibility and choice of treatment administration, building on the established safety and efficacy profile of intravenous Tecentriq.