Atezolizumab Combined With BDB001 AnD Immunogenic Radiotherapy in Patients With Advanced Solid Tumors

NCT03915678 | Recruiting Phase 2 DMC

• 2 other identifiers: IB 2019-012019-000850-78
• Study Type: interventional
• Target: 247
• Locations: 1 country
• Sites: 11

Brief Summary

Basket trial concept to independently and simultaneously assess the effects of the association of atezolizumab + BDB001 + radiotherapy in multiple solid tumors.

Conditions

Solid Tumor, Adult; Pancreatic Cancer; Virus-associated Tumors; Non Small Cell Lung Cancer; Melanoma; Bladder Cancer; Triple Negative Breast Cancer

Keywords

Immunotherapy; Radiotherapy; Oncology; Metastatic

Outcome Measures

Primary Outcomes (6)

• Assessment of the antitumor activity of atezolizumab combined with BDB001 and radiotherapy in patients with pancreatic cancer.

  Antitumor activity will be assessed in terms of disease control rate within 24 weeks of treatment onset and is defined as the proportion of patients with complete response (CR), partial response (PR) or stable disease (SD) observed within 24 weeks of treatment onset (while treated with the investigational product), based on RECIST 1.1 criteria.

  Within 6 months of treatment onset

• Assessment of the antitumor activity of atezolizumab combined with BDB001 and radiotherapy in patients with virus associated tumors.

  Antitumor activity will be assessed in terms of disease control rate within 24 weeks of treatment onset and is defined as the proportion of patients with complete response (CR), partial response (PR) or stable disease (SD) observed within 24 weeks of treatment onset (while treated with the investigational product), based on RECIST 1.1 criteria.

  Within 6 months of treatment onset

• Assessment of the antitumor activity of atezolizumab combined with BDB001 and radiotherapy in patients with non-small cell lung cancer.

  Antitumor activity will be assessed in terms of disease control rate within 24 weeks of treatment onset and is defined as the proportion of patients with complete response (CR), partial response (PR) or stable disease (SD) observed within 24 weeks of treatment onset (while treated with the investigational product), based on RECIST 1.1 criteria.

  Within 6 months of treatment onset

• Assessment of the antitumor activity of atezolizumab combined with BDB001 and radiotherapy in patients with soft-tissue sarcoma.

  Antitumor activity will be assessed in terms of 6-month progression-free rat (PFR) and is defined as the proportion of patients with complete response (CR), partial response (PR) or stable disease (SD) observed at 6 months following treatment onset and more than 24 weeks, based on RECIST 1.1 criteria.

  6 months of treatment onset

• Assessment of the antitumor activity of atezolizumab combined with BDB001 and radiotherapy in patients with bladder cancer.

  Antitumor activity will be assessed in terms of disease control rate within 24 weeks of treatment onset and is defined as the proportion of patients with complete response (CR), partial response (PR) or stable disease (SD) observed within 24 weeks of treatment onset (while treated with the investigational product), based on RECIST 1.1 criteria.

  Within 6 months of treatment onset

• Assessment of the antitumor activity of atezolizumab combined with BDB001 and radiotherapy in patients with triple negative breast cancer.

  Antitumor activity will be assessed in terms of disease control rate within 24 weeks of treatment onset and is defined as the proportion of patients with complete response (CR), partial response (PR) or stable disease (SD) observed within 24 weeks of treatment onset (while treated with the investigational product), based on RECIST 1.1 criteria.

  Within 6 months of treatment onset

Secondary Outcomes (17)

• 6-month Progression-free rate (PFR) in patients with pancreatic cancer.

  6 months

• 6-month Progression-free rate (PFR) in patients with virus-associated tumor.

  6 months

• 6-month Progression-free rate (PFR) in patients with non-small cell lung cancer.

  6 months

• 6-month Progression-free rate (PFR) in patients with bladder cancer.

  6 months

• 6-month Progression-free rate (PFR) in patients with triple negative breast cancer.

  6 months

Study Arms (6)

Population 1: Pancreatic cancer

EXPERIMENTAL

Participants with pancreatic cancer will be treated with Atezolizumab combined with BDB001 and radiotherapy.

Drug: Association atezolizumab + BDB001 + RT

Population 2: Virus-associated tumors

EXPERIMENTAL

Participants with virus-associated tumors will be treated with Atezolizumab combined with BDB001 and radiotherapy.

Drug: Association atezolizumab + BDB001+ RT

Population 3: anti-PD-1/L1 refractory non-small lung cancer

EXPERIMENTAL

Participants with anti-PD-1/L1 refractory non-small lung cancer will be treated with Atezolizumab combined with BDB001 and radiotherapy.

Drug: Association atezolizumab + BDB001+ RT

Population 4: Soft-tissue sarcoma

EXPERIMENTAL

Participants with soft-tissue sarcoma will be treated with Atezolizumab combined with BDB001 and radiotherapy.

Drug: Association atezolizumab + BDB001 + RT

Population 5: anti-PD-1/L1 refractory bladder cancer

EXPERIMENTAL

Participants with anti-PD-1/L1 refractory bladder cancer will be treated with Atezolizumab combined with BDB001 and radiotherapy.

Drug: Association atezolizumab + BDB001 + RT

Population 6: Triple negative breast cancer

EXPERIMENTAL

Participants with triple negative breast cancer will be treated with Atezolizumab combined with BDB001 and radiotherapy.

Drug: Association atezolizumab + BDB001 + RT

Interventions

Association atezolizumab + BDB001 + RT DRUG

A treatment cycle consits of 3 weeks. Atezolizumab will be administered as a 1-hour infusion on day 1 every 3 weeks (1200 mg). BDB001 will be administered by a 30-minute intravenous infusion before atezolizumab, on Days 1, 8, and 15 of cycles 1, 2, and 3. Then from cycle 4 BDB001 will be administered on Day 1 every 3 weeks. Radiotherapy will start at least one week after the first administration of atezolizumab and at the latest before the 2nd administration. All participants will be treated by high dose irradiation in stereotactic conditions on non-injected metastasis: 3 to 5 fractions for a total dose between 27 Gy and 60 Gy.

Population 1: Pancreatic cancer

Eligibility Criteria

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

You may qualify if:

• histologically confirmed pancreatic cancer, virus-associated tumors \[including papillomaviruses-related cancers (cervical, head and neck, and nasal), Epstein-Barr virus (nasopharyngeal carcinoma) and Kaposi's sarcoma-associated herpes virus), non-small cell lung cancer, soft-tissue sarcomas, bladder cancer, triple negative breast cancer. For population 4, diagnosis must be confirmed by the RRePS Network as recommended by the French NCI. For population 2, papillomavirus-related cancers must be eligible whatever the genotype but in case of viral genotype is not available, IHC p16 positive must be provided, hepatocellular carcinoma must be confirmed by Hepatite B or C infection, HHV-8 and Epstein-Barr virus related cancers must be confirmed by molecular analysis,
• Metastatic disease,
• Age ≥ 18 years,
• ECOG ≤ 1,
• At least two lesions: one extra cerebral lesion that can be treated by radiotherapy and one site of disease that must be uni-dimensionally ≥ 10 mm considered as measurable according to RECIST v1.1. This lesion will not be treated by radiotherapy, however, note that lesion(s) that will be treated by radiotherapy will also be considered as measurable. Note that the largest size of the metastases to be irradiated will be 3cm and at that previous irradiation of these lesions is not allowed,
• Life expectancy \> 6 months,
• At least one tumor site that can be biopsied for research purpose. Tumor lesion in close proximity to vascular structures such as large vessels, aneurysm or pulmonary arteriovenous malformation will not be considered for biopsy,
• Availability of archived paraffin-embedded tumor tissue for research purpose,
• Participant must have advanced disease and must not be a candidate for other approved therapeutic regimen known to provide significant clinical benefit based on investigator judgement,
• Participants who received prior anti-PD-1/L1 therapy must fulfill the following requirements - population 3 and population 5 only
• Have achieved a complete response, partial response or stable disease and subsequently had disease progression while still on anti-PD-1/L1 therapy
• Have received at least two doses of an approved anti-PD-1/L1 therapy (by any regulatory authority)
• Have demonstrated disease progression as defined by RECIST v1.1 within 18 weeks from the last dose of the anti- PD-1/L1 therapy.
• Adequate hematological, renal, metabolic and hepatic functions
• No prior or concurrent malignant disease needing an active treatment,

You may not qualify if:

• Previous treatment with a TLR agonist
• Evidence of progressive or symptomatic central nervous system (CNS) or leptomeningeal metastases,
• Women who are pregnant or breast feeding,
• Participation in a study involving a medical or therapeutic intervention in the last 30 days,
• Known hypersensitivity to CHO cell products or to any involved study drug or of its formulation components,
• History of severe allergic anaphylactic reactions to chimeric, human or humanized antibodies, or fusion proteins,
• Individuals deprived of liberty or placed under legal guardianship,
• Prior organ transplantation, including allogeneic stem cell transplantation,
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver and inherited liver disease,
• History of intra-abdominal inflammatory process within the last 12 months such as, but not limited to, diverticulitis, peptic ulcer disease or colitis.
• History of autoimmune disease including, but not limited to systemic lupus erythematosus (SLE), Sjögren's syndrome, glomerulonephritis, multiple sclerosis, rheumatoid arthritis, vasculitis, systemic immune activation, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Guillain-Barré syndrome, Bell's palsy.
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
• Poorly controlled Type II diabetes mellitus defined as a screening fasting plasma glucose ≥160 mg/dL (or 8.8 mmol/L).
• Administration of a live, attenuated vaccine within 4 weeks before the start of study medication .
• Has known active hepatitis B or hepatitis C,known history of Human Immunodeficiency or known acquired immunodeficiency syndrome, known history of tuberculosis

Sponsors & Collaborators

• Institut Bergonié: lead
• Roche Pharma AG: collaborator
• National Cancer Institute, France: collaborator
• Eikon Therapeutics: collaborator

Study Sites (11)

Institut Bergonié

Bordeaux, 33076, France

RECRUITING

Chu Brest

Brest, 29200, France

RECRUITING

Centre François Baclesse

Caen, 14076, France

RECRUITING

Centre Georges François Leclerc

Dijon, 21079, France

RECRUITING

Centre Oscar Lambret

Lille, 59020, France

RECRUITING

Hôpital La Timone

Marseille, 13005, France

NOT YET RECRUITING

Institut Paoli Calmettes

Marseille, 13273, France

RECRUITING

Institut Curie

Paris, 75005, France

NOT YET RECRUITING

CHU Poitiers

Poitiers, 86000, France

RECRUITING

Centre Eugène Marquis

Rennes, 35042, France

RECRUITING

IUCT Oncopôle

Toulouse, 31052, France

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms; Carcinoma, Non-Small-Cell Lung; Melanoma; Urinary Bladder Neoplasms; Triple Negative Breast Neoplasms; Neoplasms; Neoplasm Metastasis

Interventions

BDB001

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Breast Neoplasms; Breast Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Antoine ITALIANO, MD, PhD

CONTACT

+33 5.56.33.33.33; a.italiano@bordeaux.unicancer.fr

Simone MATHOULIN-PELISSIER, MD, PhD

CONTACT

s.mathoulin@bordeaux.unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 6 independent single-arm, multicenter, phase II trials, based on 2-stage Simon's optimal design (Simon R, Controlled Clinical Trials 1989): * Population 1: pancreatic cancer * Population 2: virus-associated tumors * Population 3: non-small lung cancer * Population 4: soft-tissue sarcoma * Population 5: bladder cancer * Population 6: triple negative breast cancer

Study Record Dates

• First Submitted: April 8, 2019
• First Posted: April 16, 2019
• Study Start: March 31, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: October 6, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (11)