Combination of Atezolizumab With Dendritic Cell Vaccine in Patients With Lung Cancer — VENEZO-LUNG  

Extensive-stage Small Cell Lung Cancer Clinical Trial

Official title: Phase Ib/II Trial of the Combination of Atezolizumab With Dendritic Cell Vaccination as Maintenance Treatment in Patients With Extensive Stage Small Cell Lung Cancer (ES-SCLC) After Induction Treatment

Status Active, not recruiting

Clinical Trial Summary

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 the dendritic cell vaccine (6 doses maximum) in combination with atezolizumab 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. Secondary Outcome Measures include: Duration of clinical benefit (DCB), Overall survival (OS) and Overall response rate (ORR)

The translational substudy will include:

Analysis of tumor tissue samples will consist of PD-L1 Immunohistochemistry testing, RNA expression, Work Environmental Scale (WES) analysis, and flow cytometry in pretreatment fresh tumor tissue.

The analysis will consist of T cell immunophenotyping, DC immunophenotyping, Tumoral RNA analysis by nanostring and tumoral cell-free DNA analysis by WES and cytokine analysis

Clinical Trial Description

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.

Treatment with atezolizumab will continue until disease progression (PD), significant clinical deterioration, unacceptable toxicity, or if any criteria for withdrawal from the trial is fulfilled.

Treatment with dendritic cell vaccines will continue for a maximum of 6 doses until PD, significant clinical deterioration, unacceptable toxicity, or if any criteria for withdrawal from the trial are fulfilled (whichever occurs first).

Treatment may continue after the initial determination of PD per RECIST 1.1 if the subject's performance status remains stable, and if the opinion of the principal investigator, the subject will benefit from continued treatment and if other criteria are fulfilled as outlined in the protocol.

For patients who have a confirmed CR or PR, it should be considered prophylactic cranial irradiation (PCI) after completion of chemotherapy (i.e., induction) based on the investigator's judgment. Following the completion of the induction part, PCI may be administered concurrently with atezolizumab and dendritic cell vaccination during the maintenance part. For those patients who have not progressed at the time of study drug discontinuation, the tumor assessments (including all disease locations) will be assessed radiologically by CT or MRI, as performed at screening, every 9 weeks (approximately 63 ± 7 days), until the occurrence of PD or study completion. The same method of assessment (CT or MRI) should be used to characterize tumors at screening and at all follow-up assessments. If positron emission tomography (PET) is used, it should also be accompanied by spiral CT or MRI.

Safety will be defined based on the rate of serious adverse events (SAEs) comparing with historic controls of atezolizumab in monotherapy as a maintenance treatment.

Kaplan Meier method will be used to estimate the survival function. Translational study

Tumor samples: All patients will undergo baseline tumor tissue acquisition prior to enrollment. The only mandatory tissue biopsy is pretreatment. Tissue samples:

Pre induction treatment fresh and paraffin-embedded tumor sample (If obtaining a fresh biopsy is not feasible, the case should be discussed with Coordinating Investigators) Pre maintenance phase (for those that rebiopsy is feasible) After 24 weeks on maintenance phase (for those patents that continue on treatment after w24 on maintenance and rebiopsy is feasible) At tumor progression (for those patients who progressed and rebiopsy is feasible).

Analysis of tumor tissue samples will consist of PD-L1 Immunohistochemistry testing, RNA expression, WES analysis, and flow cytometry in pretreatment fresh tumor tissue.

Peripheral blood samples: Peripheral blood samples will be collected:

Pre induction treatment Pre maintenance phase After 9 weeks of the first vaccination At progression of the disease The analysis will consist of T cell immunophenotyping, DC immunophenotyping, Tumoral RNA analysis by nanostring and tumoral cell-free DNA analysis by WES and cytokine analysis ;

Related Conditions & MeSH terms

• Extensive-stage Small Cell Lung Cancer
• Lung Neoplasms
• Small Cell Lung Carcinoma

• NCT number: NCT04487756
• Study type: Interventional
• Source: Instituto Oncológico Dr Rosell
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: March 17, 2021
• Completion date: October 2024