On September 12, 2024, the Food and Drug Administration sanctioned atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza, Genentech, Inc.) for subcutaneous administration for all adult indications corresponding to the intravenous formulation of atezolizumab (Tecentriq, Genentech, Inc.), encompassing non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), hepatocellular carcinoma (HCC), melanoma, and alveolar soft part sarcoma (ASPS). Refer to the prescribed information for the particular indications.
Effectiveness and Safety
The subcutaneous administration of atezolizumab and hyaluronidase-tqjs was assessed in IMscin001 (NCT03735121), an open-label, multicenter, international, randomized trial involving adult patients with locally advanced or metastatic NSCLC who had not previously received cancer immunotherapy and exhibited disease progression after platinum-based chemotherapy. A total of 371 patients were randomized in a 2:1 ratio to receive subcutaneous atezolizumab with hyaluronidase-tqjs or intravenous atezolizumab until disease progression or intolerable toxicity occurred.
The principal outcome measure was atezolizumab exposure, accompanied by coprimary pharmacokinetic (PK) endpoints of Cycle 1 Ctrough and AUC0-21days. Supplementary descriptive efficacy outcome metrics were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). The geometric mean ratio (GMR) (90% CI) of subcutaneous atezolizumab to intravenous atezolizumab for Cycle 1 Ctrough was 1.05 (0.88, 1.24), and for AUC0-21days it was 0.87 (0.83, 0.92), both of which exceeded the pre-specified criterion of 0.8 for comparability, hence satisfying the lower limit of the GMR (90% CI).
No significant variations in overall response rate, progression-free survival, or overall survival were detected across the various formulations. The confirmed overall response rate (ORR) was 9% (95% confidence interval: 5, 13) in the subcutaneous atezolizumab and hyaluronidase-tqjs group, and 8% (95% confidence interval: 4, 14) in the intravenous atezolizumab group.
The predominant adverse effects of any severity (≥ 10%) included fatigue, musculoskeletal pain, cough, dyspnea, and diminished appetite.
The advised dosage is a single 15 mL injection (comprising 1,875 mg of atezolizumab and 30,000 units of hyaluronidase) delivered subcutaneously in the thigh over about 7 minutes every 3 weeks.
Dr. Nishant Mittal is a highly accomplished researcher with over 13 years of experience in the fields of cardiovascular biology and cancer research. His career is marked by significant contributions to stem cell biology, developmental biology, and innovative research techniques.
Research Highlights
Dr. Mittal's research has focused on several key areas:
1) Cardiovascular Development and Regeneration: He studied coronary vessel development and regeneration using zebrafish models1.
2) Cancer Biology: At Dartmouth College, he developed zebrafish models for studying tumor heterogeneity and clonal evolution in pancreatic cancer.
3) Developmental Biology: His doctoral work at Keio University involved identifying and characterizing medaka fish mutants with cardiovascular defects.
4) Stem Cell Research: He investigated the effects of folic acid on mouse embryonic stem cells and worked on cryopreservation techniques for hematopoietic stem cells.
Publications and Presentations
Dr. Mittal has authored several peer-reviewed publications in reputable journals such as Scientific Reports, Cardiovascular Research, and Disease Models & Mechanisms1. He has also presented his research at numerous international conferences, including the Stanford-Weill Cornell Cardiovascular Research Symposium and the Weinstein Cardiovascular Development Conference.
In summary, Dr. Nishant Mittal is a dedicated and accomplished researcher with a strong track record in cardiovascular and cancer biology, demonstrating expertise in various model systems and a commitment to advancing scientific knowledge through innovative research approaches.
