Subcutaneous Atezolizumab Produces Noninferior Pharmacokinetics Vs IV Atezolizumab in NSCLC

The subcutaneous administration of atezolizumab produced non-inferior levels of the agent in the blood compared with intravenous atezolizumab in immunotherapy-naïve patients with locally advanced or metastatic non–small cell lung cancer who failed platinum-based chemotherapy.

The subcutaneous administration of atezolizumab (Tecentriq) produced non-inferior levels of the agent in the blood compared with intravenous (IV) atezolizumab in immunotherapy-naïve patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) who failed platinum-based chemotherapy, according to data from the phase 3 IMscin001 trial (NCT03735121).1

When given subcutaneously, atezolizumab can be administered in 3-8 minutes per injection vs the 30-60 minutes required for an IV dose. Detailed findings from the study will be presented at an upcoming medical meeting.

“By reducing the administration time, this new [atezolizumab] formulation could help save time for patients and healthcare systems,” Levi Garraway, MD, PhD, the chief medical officer and head of Global Product Development at Roche, stated in a press release. “We are excited by the potential of bringing a subcutaneous cancer immunotherapy to patients globally, delivering on our commitment to improve the treatment experience for patients.”

IV atezolizumab has been FDA approved in multiple indications for the treatment of patients with NSCLC, including for use in combination with bevacizumab (Avastin), carboplatin, and paclitaxel (ABCP) for the first-line treatment of patients with metastatic nonsquamous NSCLC in December 20182, and for use as an adjuvant treatment following resection and platinum-based chemotherapy in patients with stage II to IIIA NSCLC whose tumors have PD-L1 expression on 1% or more of tumor cells in October 2021.3

The investigational subcutaneous formulation of atezolizumab combines the agent with Halozyme Therapeutics’ Enhanze® drug delivery technology. The phase 1b/3 global, multi-center, randomized IMscin001 study evaluated the pharmacokinetics, safety, and efficacy of the subcutaneous formulation of atezolizumab compared with the IV formulation.

The trial enrolled adult patients aged 18 years or older with histologically or cytologically documented locally advanced or metastatic NSCLC with measurable disease per RECIST v1.1 criteria who had a prior platinum-containing regimen or disease recurrence within 6 months since a prior platinum-based adjuvant/neoadjuvant regimen (n = 371).4 Patients were also required to have an ECOG performance status of 0 or 1, a life expectancy of at least 12 weeks, and adequate hematologic and end-organ function.

Key exclusion criteria included symptomatic, untreated, or actively progressing central nervous system metastases; uncontrolled or symptomatic hypercalcemia; pregnancy or breastfeeding; active or history of autoimmune disease or immune deficiency; history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis; severe infection within 4 weeks of study treatment; treatment with therapeutic oral or IV antibiotics within 2 weeks of the start of study treatment; significant cardiovascular disease; or prior allogeneic stem cell or solid organ transplantation.

The co-primary end points of the study were minimum levels of atezolizumab in the blood during a given dosing interval based on established pharmacokinetic measurements and area under the concentration-time curve from 0 to 21 days. Secondary end points included safety, immunogenicity, patient-reported outcomes, overall response rate, overall survival, progression-free survival, and duration of response.

The press release noted that the safety profile of the subcutaneous formulation of atezolizumab was consistent with the known safety of the IV formulation.

References

  1. Roche’s subcutaneous formulation of Tecentriq demonstrates positive phase III results. News release. Roche. August 2, 2022. Accessed August 2, 2022. https://bit.ly/3zR5w05
  2. FDA approves atezolizumab with chemotherapy and bevacizumab for first-line treatment of metastatic non-squamous NSCLC. News release. FDA. December 6, 2018. Accessed August 2, 2022. https://bit.ly/3bpeZSV
  3. FDA approves atezolizumab as adjuvant treatment for non-small cell lung cancer. News release. FDA. October 15, 2021. Accessed August 2, 2022. https://bit.ly/3lHUgvQ
  4. A study to investigate atezolizumab subcutaneous in patients with previously treated locally advanced or metastatic non-small cell lung cancer. ClinicalTrials.gov. Updated June 10, 2022. Accessed August 2, 2022. https://clinicaltrials.gov/ct2/show/NCT03735121