FDA Approves Atezolizumab and Hyaluronidase-Tqjs for Subcutaneous Injection
On September 12, 2024, the U.S. Food and Drug Administration (FDA) approved (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-atezolizumab-and-hyaluronidase-tqjs-subcutaneous-injection) atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza) for subcutaneous injection for all the adult indications for the IV formulation of atezolizumab (Tecentriq®), including non-small cell lung cancer (NSCLC), small cell lung cancer, hepatocellular carcinoma, melanoma, and alveolar soft part sarcoma. See the prescribing information, which will be posted on will be posted on Drugs@FDA (https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm), for all of the indications.
The subcutaneous injection (https://voice.ons.org/news-and-views/07-2024/administration-considerations-amid-the-large-volume-subcutaneous-injection) formulation was evaluated in IMscin001 (NCT03735121), an open-label, multicenter, international, randomized trial in 371 adult patients with locally advanced or metastatic NSCLC who were not previously exposed to cancer immunotherapy and who had disease progression following treatment with platinum-based chemotherapy. Patients were randomized 2:1 to receive subcutaneous atezolizumab and hyaluronidase-tqjs or IV atezolizumab until they experienced disease progression or unacceptable toxicity.
The primary outcome measure was atezolizumab exposure, with coprimary pharmacokinetic (PK) endpoints of cycle 1Ctrough and AUC0–21days. Additional descriptive efficacy outcome measures were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). The geometric mean ratio (90% CI) of subcutaneous atezolizumab and IV atezolizumab for cycle 1Ctrough was 1.05 (0.88, 1.24) and AUC0–21days was 0.87 (0.83, 0.92), which met the lower limit of the geometric mean ratio (90% CI) above the prespecified threshold of 0.8 for comparability. The researchers did not observe any notable differences in ORR, PFS, or OS between the different formulations. They confirmed an ORR of 9% (95% CI = 5, 13) in the subcutaneous atezolizumab and hyaluronidase-tqjs arm and 8% (95% CI = 4, 14) in the IV atezolizumab arm.
The most common adverse reactions of any grade reported in at least 10% of patients were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite.
The recommended dosage is one 15 ml injection (containing 1,875 mg of atezolizumab and 30,000 units of hyaluronidase) administered subcutaneously in the thigh over approximately seven minutes once every three weeks. See the full prescribing information, which will be posted on Drugs@FDA (https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm), for all of the administration considerations. Additionally, check out ONS Voice’s “Make Subcutaneous Administration More Comfortable for Your Patients (https://voice.ons.org/news-and-views/01-2022/make-subcutaneous-administration-more-comfortable-for-your-patients)” for nursing-specific factors.
The applicant used the Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid) to facilitate the FDA’s review of the application.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.
For assistance with single-patient applications for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).