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

NCT04487756 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: IOR-IISML420372020-000448-72
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

Brief 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

Conditions

Extensive-stage Small Cell Lung Cancer

Keywords

Small cell lung cancer; Atezolizumab; Dendritic cell vaccine; Safety; Efficacy

Outcome Measures

Primary Outcomes (2)

• Progression-Free Survival (PFS) rate at 6 months

  Calculated as the percentage of participants alive and without disease progression, as assessed by the Investigator using RECIST v1.1

  At 6 months after start of treatment

• Frequency and severity of AEs and SAEs (Safety)

  he number of patients with AEs and SAEs, changes in laboratory values, vital signs, ECGs, and results of physician examinations graded according to the CTCAE v 5.0.

  Throughout the study. Approximately 3 years

Secondary Outcomes (4)

• Duration of clinical benefit (DCB) as per RECIST 1.1

  Throughout the study. Approximately 3 years

• Overall Survival (OS)

  Throughout the study. Approximately 3 years

• Objective response rate (ORR1) as per RECIST 1.1

  Throughout the study. Approximately 3 years

• Objective response rate (ORR2) as per RECIST 1.1

  Throughout the study. Approximately 3 years

Study Arms (1)

Atezo+DCvac

EXPERIMENTAL

\- Induction (4 cycles, every 3 weeks): Carboplatin area under the curve (AUC) 5 (5 mg per milliliter per minute, administered intravenously on day 1 of each cycle) and etoposide (100 mg per square meter of body-surface area, administered intravenously on days 1 through 3 of each cycle) Atezolizumab, 1200 mg administered intravenously every 3 weeks on day 1 of each cycle) \- Maintenance (only patients without PD after 4 induction cycles, up to PD): Atezolizumab iv (1200 mg/IV on day 1 every 3 weeks) DCV intradermally (max. 6 doses) on weeks 1, 3, 6, 9, 21, 33.

Drug: Atezolizumab 1200 mg in 20 ML Injection; Biological: ADC Vaccine; Drug: Carboplatin

Interventions

Atezolizumab 1200 mg in 20 ML Injection DRUG

\- Induction (4 cycles, every 3 weeks): Atezolizumab, 1200 mg administered intravenously every 3 weeks on day 1 of each cycle) \- Maintenance (only patients without PD after 4 induction cycles, up to PD): Atezolizumab iv (1200 mg/IV on day 1 every 3 weeks)

Also known as: Tecentriq

Atezo+DCvac

ADC Vaccine BIOLOGICAL

\- Maintenance (only patients without PD after 4 induction cycles, up to PD): DCV intradermally (max. 6 doses) on weeks 1, 3, 6, 9, 21, 33.

Also known as: Autologous Dendritic cell (ADC) vaccine, Dendritic cell (DC) vaccine

Atezo+DCvac

Carboplatin DRUG

\- Induction (4 cycles, every 3 weeks): Carboplatin AUC 5 (5 mg per milliliter per minute, administered intravenously on day 1 of each cycle) and etoposide (100 mg per square meter of body-surface area, administered intravenously on days 1 through 3 of each cycle)

Also known as: Carboplatino (Teva/Accord/Pharmacia)

Atezo+DCvac

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological diagnosis of extensive-stage small cell lung cancer (ES-SCLC). Unequivocally confirmed diagnosis of SCLC by histology preferably including the presence of neuroendocrine features by immunohistochemistry.
• Centrally confirmed tumor tissue viability for vaccine preparation.
• No previous cancer treatment for advanced disease
• Life expectancy at least 16 weeks
• ECOG performance status 0 or 1.
• Adequate normal organ and marrow function as defined below:
• Absolute neutrophil count ≥ 1.5 x 109 cells/L Platelets ≥ 100 x 109/L Hemoglobin ≥ 9 g/dL Aspartate and alanine aminotransferases (AST, ALT) ≤ 2.5 x upper limit of normal (ULN) (≤ 5 x ULN, if documented liver metastases are present) Total bilirubin ≤ 2 x ULN (except patients with documented Gilbert's syndrome) Creatinine \< 2 mg/dl (or a glomerular filtration rate \> 60)
• Prior palliative radiotherapy must have been completed at least 2 weeks prior to start the study treatment (subjects may receive localized palliative radiotherapy while receiving study drug).
• Subjects with brain metastases are eligible if they are asymptomatic, are treated, or are neurological stable for at least 2 weeks without the use of steroids, or on a stable or decreasing dose of \< 10 mg daily prednisone or equivalent.
• Must be willing and able to accept one leukapheresis procedures
• Written informed consent of approved by the investigator's Institutional Review Board (IRB)/Independent Ethics Committee (IEC), prior to the performance of any trial activities.
• Male or female subjects aged ≥ 18 years.
• Measurable disease by RECIST.1.1 criteria.
• Highly effective contraception for both male and female subjects throughout the study and for at least 30 days after the last atezolizumab treatment administration if the risk of conception exists.
• Negative serum pregnancy test at screening for women of childbearing potential. Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: ≥60 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.

You may not qualify if:

• Prior chemotherapy for extensive-stage ES-SCLC
• Any prior anti-PD-1/PD-L1 antibody therapy
• History of, or significant evidence of risk for, severe chronic inflammatory or autoimmune disease
• Potential requirement for systemic corticosteroids or concurrent immunosuppressive drugs based on prior history or received systemic steroids within the last 2 weeks prior to enrollment (inhaled or topical steroids at standard doses are allowed)
• Human immunodeficiency virus (HIV) seropositivity, active Hepatitis B or C seropositivity
• Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol
• Pregnancy or breastfeeding; female patients must be surgically sterile or be postmenopausal for two years or must agree to use effective contraception during the period of treatment and 6 months after; all female patients with reproductive potential must have a negative pregnancy test (serum/urine) within 24 hours from starting the conditioning chemotherapy; the definition of effective contraception will be based on the judgment of the study investigators; patients who are breastfeeding are not allowed on study
• Any unresolved toxicity (CTCAE grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripheral neuropathy).
• Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. For phase I cohort, patients with autoimmune paraneoplastic syndromes will be also excluded.
• Any syndrome that requires systemic corticosteroid/immunosuppressive medication EXCEPT for syndromes which would not be expected to recur in the absence of an external trigger (vitiligo, autoimmune thyroiditis, or type 1 diabetes mellitus are permitted to enroll)
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
• History of primary immunodeficiency.
• History of allogeneic organ transplant. 14 History of hypersensitivity to atezolizumab / ADC vaccine or any excipient.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diathesis including any subject known to have evidence of acute or chronic hepatitis B or C or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
• Known history of active tuberculosis. 17- Subjects with previous malignancies (except for non-melanoma skin cancer, and cancer in situ of the bladder, gastric, colon, cervical/dysplasia, melanoma, breast) are excluded unless a complete remission was achieved at least 5 years prior to study entry and no additional therapy is required or anticipated to be required during the study period.

Sponsors & Collaborators

• Instituto Oncológico Dr Rosell: lead
• Roche Pharma AG: collaborator
• Fundacion Clinic per a la Recerca Biomédica: collaborator

Study Sites (3)

ICO Badalona

Badalona, Barcelona, 08916, Spain

Location

Quirón Dexeus

Barcelona, 08028, Spain

Location

Hospital Clínic Barcelona

Barcelona, 08036, Spain

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

atezolizumab; Injections; arginine decarboxylase; Vaccines; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Biological Products; Complex Mixtures; Coordination Complexes; Organic Chemicals

Study Officials

• María González Cao

  Hospital Quirón-Dexeus

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: single arm Phase Ib/II multicenter open label study, with translational sub-study

Study Record Dates

• First Submitted: July 22, 2020
• First Posted: July 27, 2020
• Study Start: March 17, 2021
• Primary Completion: August 1, 2024
• Study Completion: October 1, 2024
• Last Updated: April 3, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (3)