An Analysis of Subcutaneous Versus Intravenous Atezolizumab in NSCLC

The ongoing search for more efficient and patient-friendly delivery of cancer immunotherapies has led to growing interest in subcutaneous (SC) formulations of established treatments. Atezolizumab, a PD-L1 inhibitor, is approved for intravenous (IV) administration across multiple solid tumors, but its potential may be expanding with results from the IMscin001 trial, which was designed to compare SC versus IV atezolizumab in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). Here’s what the trial found on the safety, efficacy, and clinical applications of these two options.

Design and Timeline of the IMscin001 Study

IMscin001 enrolled 371 immunotherapy-naïve NSCLC patients who had progressed on platinum-based chemotherapy. Patients were randomized 2:1 to receive either SC atezolizumab (1875 mg, n = 247) or IV atezolizumab (1200 mg, n = 124) every three weeks.

This two-part trial consisting of phase Ib and phase III studies was completed in November 2024, with earlier data releases providing key updates along the way.

Updated results from the phase III portion were published in May of 2024 based on data collected through January of 2023, offering insights into the comparative efficacy, safety, and practicality of SC versus IV atezolizumab. With mature overall survival data, these findings confirmed previous pharmacokinetic equivalence while also providing new perspectives from patient-reported outcomes and healthcare provider assessments. The results led to FDA approval of SC atezolizumab in September 2024.

Despite these findings, the complete trial data have yet to be published, and the final results are highly anticipated as they may further clarify SC atezolizumab’s long-term role in clinical practice.

Key Findings of the Study

Regarding the results, efficacy outcomes were comparable between SC and IV atezolizumab, with a median follow-up of 9.5 months. This confirms that SC delivery maintained treatment efficacy and could potentially serve as a practical alternative to IV therapy. The findings showed that:

• Median overall survival was 10.7 months with SC treatment compared to 10.1 months with IV treatment (HR: 0.88; 95 percent CI: 0.67–1.16).
• Median progression-free survival was 2.8 months with SC treatment compared to 2.9 months with IV treatment (HR: 1.05; 95 percent CI: 0.83–1.33).
• Objective response rate was 11.0 percent with SC treatment compared to 10.5 percent with IV treatment.

Safety and Immunogenicity Considerations

Looking at safety, SC atezolizumab demonstrated a similar safety profile to IV administration, with potential advantages in tolerability. The study found that:

• Grade three to four adverse events occurred in 20.6 percent of patients receiving SC atezolizumab versus 31.5 percent of patients receiving IV atezolizumab.
• Serious adverse events occurred in 19.4 percent of patients receiving SC atezolizumab versus 27.4 percent of patients receiving IV atezolizumab.

Notably, no infusion-related reactions occurred in the SC arm, compared to 3.2 percent in the IV group. Injection-site reactions were minimal at 4.5 percent and mostly Grade 1 in the SC arm, whereas none were reported in the IV arm.

The immunogenicity profile showed a slightly higher occurrence of anti-drug antibodies in the SC arm (20.6 percent versus 14.3 percent), but this had no observed impact on pharmacokinetics, efficacy, or safety.

Practical Advantages

When considering the applications of this research, one of the benefits of SC administration was its reduced treatment time. The median administration time for SC atezolizumab was 7.1 minutes, compared to 40 minutes for IV infusion. Most patients received their SC injections within four to eight minutes, a major efficiency gain for both patients and clinics.

Additionally, a survey of 44 healthcare professionals revealed strong support for SC administration of atezolizumab. The majority of them found it a convenient and easy-to-administer option, with most expressing satisfaction with the treatment. Many also noted the time difference between SC administration and IV infusion, highlighting SC treatment’s potential to improve workflow efficiency in clinical settings.

The Future of SC Atezolizumab

With the final IMscin001 trial data yet to be published, oncologists and treatment centers are awaiting further insights on the role of SC atezolizumab for patients with NSCLC, especially after it showed promising safety and efficacy results in the data from early 2024. As oncology treatments advance toward more efficient and patient-centered approaches, the forthcoming results from the full trial analysis will provide a clearer picture of SC administration’s long-term impact and potential advantages in clinical settings.

References:

1. Burotto M, Zvirbule Z, Alvarez R, et al. b=Brief report: updated data from IMscin001 part 2, a randomized phase III study of subcutaneous versus intravenous atezolizumab in patients with locally advanced or metastatic NSCLC. J Thorac Oncol. 2024;19(10):1460-1466. doi:10.1016/j.jtho.2024.05.005
2. FDA approves atezolizumab and hyaluronidase-tqjs for subcutaneous injection. Food and Drug Administration. September 12, 2024. Accessed March 10, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-atezolizumab-and-hyaluronidase-tqjs-subcutaneous-injection
3. Hoffman-La Roche. A Study to Investigate Atezolizumab Subcutaneous in Patients With Previously Treated Locally Advanced or Metastatic Non-Small Cell Lung Cancer. ClinicalTrials.gov identifier: NCT03735121. Updated January 24, 2025. Accessed March 10, 2025. https://clinicaltrials.gov/study/NCT03735121