Subcutaneous Atezolizumab Non-Inferior to IV Formulation in Locally Advanced or Metastatic NSCLC

In the phase 3 IMscin001 clinical trial, the use of subcutaneous atezolizumab demonstrated similar efficacy, safety, and pharmacokinetics compared with intravenous atezolizumab in patients with immunotherapy-naïve locally advanced or metastatic non—small cell lung cancer.

A study of subcutaneous formulation of atezolizumab (Tecentriq) vs intravenous (IV) atezolizumab infusion in patients with immunotherapy-naïve patients with locally advanced or metastatic non—small cell lung cancer (NSCLC) for whom prior platinum therapy has failed has achieved its coprimary end points, according to a press release by Roche.1

Results from the study will be presented during an upcoming medical meeting and shared with regulatory authorities.

The key goal of the randomized, multicenter, phase 1b/3 study (IMscin001, NCT03735121) is to investigate the pharmacokinetics, efficacy, and safety of the subcutaneous formulation of atezolizumab compared with the IV formulation. The study is conducted in 2 parts with part 1 of IMscin001 as the dose-finding portion, and part 2 as the dose confirmation portion.2

The study includes approximately 427 patients who were assessed for the coprimary end points of observed concentration of atezolizumab in serum at cycle 1 in part 1, observed concentration of atezolizumab in serum at cycle part 2, and area under the concentration-time curve from time 0 to 21 days of atezolizumab in part 2. The secondary end points of the study are safety, immunogenicity, patient-reported outcomes, and efficacy determined by overall survival, objective response rate, and duration of response.

Patients were required to have histologically or cytologically documented locally advanced or metastatic NSCLC to be eligible for inclusion in the study. In addition, patients must have had prior treatment with a platinum-containing regimen or disease recurrence ≤ 6 months since prior platinum-based adjuvant/neoadjuvant regimen, measurable disease per RECIST v1.1, an ECOG performance status of 0 or 1, a life expectancy ≥ 12 weeks, adequate hematologic and end-organ function, and available tissue to test EGFR status during part 2.

Those excluded from the IMscin001 study were patients with conditions like symptomatic, untreated, or actively progressing central nervous system metastases, uncontrolled or symptomatic hypercalcemia, active or history of autoimmune disease or immune deficiency, severe infection ≤ 4 weeks, significant cardiovascular disease, or history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis. Patients who were treated with a live, attenuated vaccine ≤ 4 weeks, systemic immunostimulatory agents ≤ 4 weeks or 5 half-lives of the drug, systemic immunosuppressive medication ≤ 2 weeks, or therapeutic oral or IV antibiotics ≤ 2 weeks prior to study treatment, were not eligible to receive treatment in the study. Further, patients who underwent prior allogeneic stem cell or solid organ transplantation were not permitted to enroll in the study.

According to Roche, the subcutaneous administration of atezolizumab can reduce the treatment time to 3-8 minutes per injection vs a 30- to 60-minuted IV infusion with the standard formulation of the drug. In multiple studies, it has been shown that subcutaneous injection is the preferred treatment formulation of patients with care. Subcutaneous administration of treatment can also limit pain and discomfort vs standard IV treatment.1

“By reducing the administration time, this new Tecentriq formulation could help save time for patients and healthcare systems,” said Levi Garraway, MD, PhD, chief medical officer and head of global product development at Roche, 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.”

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/3oQqHJw

2. 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