A Study to Investigate Atezolizumab Subcutaneous in Patients With Previously Treated Locally Advanced or Metastatic Non-Small Cell Lung Cancer

This study will evaluate the pharmacokinetics, safety, and efficacy of atezolizumab subcutaneous (SC) compared with atezolizumab intravenous (IV) in participants with locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) who have not been exposed to cancer immunotherapy (CIT) and for whom prior platinum-based therapy has failed. The study is comprised of two parts, as follows: A dose-finding part (Part 1, Phase Ib) will aim to identify the dose of atezolizumab SC to be tested in Part 2. A dose-confirmation part (Part 2, Phase III, randomized) will aim to confirm that the dose moved forward from Part 1 yields drug exposure that is comparable to that of atezolizumab IV.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Histologically or cytologically documented locally advanced or metastatic NSCLC
* Prior platinum-containing regimen or disease recurrence ≤ 6 months since prior platinum-based adjuvant/neoadjuvant regimen.
* Measurable disease as defined by RECIST v1.1
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Life expectancy ≥12 weeks
* Adequate hematologic and end-organ function

Additional Inclusion Criteria (Part 2 Only) • Availability of tissue and known epidermal growth factor receptor (EGFR) status

Exclusion Criteria:

* Symptomatic, untreated, or actively progressing central nervous system (CNS) 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 ≤ 4 weeks
* Treatment with therapeutic oral or IV antibiotics ≤ 2 weeks prior to study treatment
* Significant cardiovascular disease
* Prior allogeneic stem cell or solid organ transplantation
* Treatment with a live, attenuated vaccine ≤ 4 weeks
* Treatment with systemic immunostimulatory agents ≤ 4 weeks or 5 half-lives of the drug
* Treatment with systemic immunosuppressive medication ≤ 2 weeks

Additional Exclusion Criteria (Part 2 Only)

• Tested tumor programmed death-ligand-1 (PD-L1) expression status with an intention to treat the patient if positive

• DERIVEDBurotto M, Zvirbule Z, Alvarez R, Chewaskulyong B, Felip E, Majem M, Korbenfeld E, Kolb-Sielecki J, Isla D, Barata T, Bustillos A, Herraez-Baranda LA, Tosti N, Young F, Zanghi J, Cappuzzo F. Efficacy and safety of subcutaneous and intravenous administration of atezolizumab in patients with non-small cell lung cancer, including early-stage, locally advanced or metastatic disease: Updated results of the IMscin001 and IMscin002 randomized studies. Lung Cancer. 2026 Jul;217:109452. doi: 10.1016/j.lungcan.2026.109452. Epub 2026 May 12. PMID 42214243
• DERIVEDBurotto M, Zvirbule Z, Alvarez R, Chewaskulyong B, Herraez-Baranda LA, Shearer-Kang E, Liu X, Tosti N, Williams P, Castro Sanchez AY, Zanghi J, Felip E. 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 Oct;19(10):1460-1466. doi: 10.1016/j.jtho.2024.05.005. Epub 2024 May 9. PMID 38729426
• DERIVEDBurotto M, Zvirbule Z, Mochalova A, Runglodvatana Y, Herraez-Baranda L, Liu SN, Chan P, Shearer-Kang E, Liu X, Tosti N, Zanghi JA, Leutgeb B, Felip E. IMscin001 Part 2: a randomised phase III, open-label, multicentre study examining the pharmacokinetics, efficacy, immunogenicity, and safety of atezolizumab subcutaneous versus intravenous administration in previously treated locally advanced or metastatic non-small-cell lung cancer and pharmacokinetics comparison with other approved indications. Ann Oncol. 2023 Aug;34(8):693-702. doi: 10.1016/j.annonc.2023.05.009. Epub 2023 Jun 1. PMID 37268157
• DERIVEDFelip E, Burotto M, Zvirbule Z, Herraez-Baranda LA, Chanu P, Kshirsagar S, Maiya V, Chan P, Pozzi E, Marchand M, Monchalin M, Tanaka K, Tosti N, Wang B, Restuccia E. Results of a Dose-Finding Phase 1b Study of Subcutaneous Atezolizumab in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer. Clin Pharmacol Drug Dev. 2021 Oct;10(10):1142-1155. doi: 10.1002/cpdd.936. Epub 2021 Mar 31. PMID 33788415