Combination of Atezolizumab With Dendritic Cell Vaccine in Patients With Lung Cancer

This is a single-arm Phase Ib/II multicenter open-label study, with translational sub-study, of atezolizumab plus autologous dendritic cell vaccine as maintenance treatment in extensive-stage small cell lung cancer (ES-SCLC). It is expected that three Spanish sites will include patients in this study.

Patients will receive standard treatment with carboplatin and etoposide, plus atezolizumab for four 21-day cycles (induction phase), followed by a maintenance phase during which they will receive atezolizumab and dendritic cell vaccine combination until they had unacceptable toxic effects, disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, or no additional clinical benefit. The two primary endpoints are the investigator-assessed toxicity and the 6 months PFS, both in the intention-to-treat population.

In the Phase Ib safety lead-in portion, up to 6 patients will be enrolled into and evaluated for dose-limiting toxicities (DLT) during the first 2 cycles of the maintenance therapy. If \<2 out of 6 patients present with limiting toxicities, the administration of the investigational products will be deemed safe in the Phase 1b lead-in, therefore enrollment will be expanded into the Phase 2 cohort. Inclusion and treatment of up to 20 patients (including those enrolled in the Phase Ib lead-in) with atezolizumab and dendritic cell vaccination as maintenance therapy is finally expected.

Safety assessments will be based on adverse event reports, results of clinical laboratory tests, immune safety tests, physical examinations, vital sign measurements, Eastern Cooperative Oncology Group (ECOG) performance status both during the study, and up to six months following the last study drug administration. Adverse events (AEs) will be assessed throughout the study period and evaluated by using National Cancer Institute (NCI) Common Technology Criteria version of Adverse Events version 5.0 (NCI CTCAE v 5.0).

Tumor measurements will be performed by computed tomography (CT) scan at baseline, at week 6 (W6), at week 12 (W12), and every 9 weeks thereafter, to evaluate 6m PFS and response to treatment. The response will be evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) and the immune-related response criteria (irRECIST) as a secondary endpoint. Brain magnetic resonance imaging (MRI) will be performed at baseline (mandatory as per clinical practice), and along with CT scan at each timepoint, if there are brain metastasis at baseline.

Patients with stable disease (SD), partial response (PR) or complete response (CR) after induction with chemotherapy plus atezolizumab (CT scan on W12) will continue during the maintenance phase with atezolizumab plus dendritic cell vaccine.