FDA Approves Genentech's Tecentriq Hybreza, First Subcutaneous Anti-PD-(L)1 Immunotherapy
核心洞察
The FDA has approved Tecentriq Hybreza, a subcutaneous formulation of atezolizumab, marking the first subcutaneous anti-PD-(L)1 cancer immunotherapy in the U.S.
Tecentriq Hybreza reduces treatment time to approximately 7 minutes via subcutaneous injection, compared to 30-60 minutes for intravenous infusion.
Approval was based on the IMscin001 study, demonstrating comparable efficacy, safety, and blood concentration levels to intravenous Tecentriq.
Genentech, a member of the Roche Group, has received FDA approval for Tecentriq Hybreza (atezolizumab and hyaluronidase-tqjs), the first and only PD-(L)1 inhibitor administered via subcutaneous injection for cancer patients in the United States. This new formulation offers a significantly shorter treatment time of approximately seven minutes, compared to the 30-60 minutes required for the standard intravenous (IV) infusion of Tecentriq (atezolizumab). Tecentriq Hybreza is approved for all IV indications of Tecentriq in adults, covering certain types of lung, liver, skin, and soft tissue cancers.
Clinical Data Supporting Approval
The FDA approval was primarily based on data from the Phase IB/III IMscin001 study. This global, multicenter, randomized trial evaluated the pharmacokinetics, safety, and efficacy of Tecentriq Hybreza compared to IV Tecentriq in patients with previously treated locally advanced or metastatic non-small cell lung cancer (搜索) (NSCLC) whose prior platinum therapy had failed. The study, involving 371 patients, met its primary endpoints by demonstrating comparable levels of Tecentriq in the blood during a given dosing interval, based on established pharmacokinetic measurements, including observed serum Ctrough and model-predicted area under the curve. Efficacy, measured by overall response rate, progression-free survival, overall survival, and duration of response, was similar between the subcutaneous and IV treatment arms, consistent with the known profile of IV Tecentriq. The safety profile of Tecentriq Hybreza was also consistent with that of IV Tecentriq.
Patient Preference and Experience
Further supporting the approval was the Phase II IMscin002 study, a global crossover trial evaluating patient preference between the subcutaneous and IV formulations of Tecentriq. This study enrolled 179 patients, including those with PD-L1 (搜索)-positive resected Stage II-IIIB NSCLC who had completed adjuvant platinum-based chemotherapy without disease recurrence, and untreated patients with PD-L1-high Stage IV NSCLC. The study met its primary endpoint, with 71% of participants preferring the subcutaneous formulation. The most common reasons cited were less time in the clinic, increased comfort during treatment, and reduced emotional distress. Furthermore, 79% of patients chose Tecentriq Hybreza to complete their treatment after experiencing both formulations, and the study confirmed that switching between Tecentriq Hybreza and IV Tecentriq was well-tolerated, with no new safety signals.
Expert Commentary
Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development, stated, "By enabling subcutaneous administration for a cancer immunotherapy, Tecentriq Hybreza now offers patients with multiple cancer types and their physicians greater flexibility and choice of treatment administration. We are pleased to introduce this new subcutaneous formulation that builds on the established safety and efficacy profile of intravenous Tecentriq and can treat patients faster and in more accessible settings."
Ann Fish-Steagall, RN, senior vice president of Patient Services at the LUNGevity Foundation, added, "This approval represents a significant option to improve the patient experience. When patients have options, they feel empowered to be vital participants in their own care and choose their preferred treatment option."
Mechanism of Action
Tecentriq Hybreza combines Tecentriq with Halozyme Therapeutics’ Enhanze drug delivery technology. Tecentriq is a monoclonal antibody designed to bind with the protein PD-L1 (搜索), expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 (搜索) and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the re-activation of T cells. The Enhanze drug delivery technology is based on a proprietary recombinant human hyaluronidase PH20 (rHuPH20), an enzyme that locally and temporarily degrades hyaluronan in the subcutaneous space, increasing tissue permeability and allowing Tecentriq to be rapidly dispersed and absorbed into the bloodstream.
Broader Implications
The approval of Tecentriq Hybreza marks a significant advancement in cancer immunotherapy, offering a more convenient and patient-friendly administration option without compromising efficacy or safety. This subcutaneous formulation has already been approved in over 50 countries outside the U.S. and is expected to streamline treatment processes and improve the overall experience for cancer patients.