Atezolizumab combined with BDB001 and immunogenic radiotherapy in participants with advanced solid tumors.
- Conditions
- - pancreatic cancer- virus-associated tumors- non-small cell lung cancer- soft-tissue sarcoma- bladder cancer- Triple negative breast cancerMedDRA version: 20.0Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: LLTClassification code 10033605Term: Pancreatic cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10039494Term: Sarcoma NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: PTClassification code 10005012Term: Bladder cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-000850-78-FR
- Lead Sponsor
- Institut Bergonié
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 247
1. Histology: histologically confirmed pancreatic cancer (population 1), virus-associated tumors (population 2), non-small cell lung cancer (population 3), soft-tissue sarcomas (population 4), bladder cancer (population 5), triple negative breast cancer (population 6). For population 4, diagnosis must be confirmed by the RRePS Network as recommended by the French NCI,
2. Metastatic disease,
3. Age = 18 years,
4. ECOG, Performance status = 1,
5. At least two lesions: one 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 (outside any previously irradiated field, except if progressive as per RECIST v1.1 at inclusion). 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,
6. Life expectancy > 6 months,
7. At least one tumor site that can be biopsied for research purpose,
8. Availability of archived paraffin-embedded tumor tissue for research purpose,
9. 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,
10. Participants who received prior anti-PD-1/L1 therapy must fulfill the following requirements
- 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.
11. Adequate hematological, renal, metabolic and hepatic functions:
12. No prior or concurrent malignant disease needing an active treatment,
13. At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment and/or radiotherapy,
14. Recovery to grade = 1 from any adverse event (AE) derived from previous treatment, excluding alopecia of any grade and non-painful peripheral neuropathy grade = 2 (according to the National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE, version 5.0)),
15. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to inclusion. Note that serum pregnancy test must be repeated 72 hours prior to receiving the first dose of study medication,
16. Both women and men must agree to use an effective method of contraception throughout the treatment period and for five months after discontinuation of treatment. Acceptable methods for contraception include intrauterine device (IUD), oral contraceptive, subdermal implant and double barrier. Participants of childbearing potential are those who have not been surgically sterilized (e.g., vasectomy for males and hysterectomy for females) or have not been free from menses for = 1 year.
17. Voluntary signed and dated written informed consents prior to any specific study procedure,
18. Participants with a social security in compliance with the French law.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 164
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 83
1. Previous treatment with a TLR agonist
2. Evidence of progressive or symptomatic central nervous system (CNS) or leptomeningeal metastases,
3. Women who are pregnant or breast feeding,
4. Participation in a study involving a medical or therapeutic intervention in the last 30 days,
5. Previous enrolment in the present study,
6. Participant unable to follow and comply with the study procedures because of any geographical, familial, social or psychological reasons,
7. Known hypersensitivity to CHO cell products or to any involved study drug or of its formulation components,
8. History of severe allergic anaphylactic reactions to chimeric, human or humanized antibodies, or fusion proteins,
9. Treatment with systemic immunosuppressive medications including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF agents within 2 weeks prior to inclusion.
10. Major surgical procedure, open biopsy or significant traumatic injury within 28 days before inclusion,
11. Any of the following cardiac criteria:
- Congestive heart failure = New York Heart Association (NYHA) class 2,
- Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months),
- Myocardial infarction less than 6 months before inclusion
- Uncontrolled cardiac arrhythmias,
- Known left ventricular ejection fraction (LVEF) <50%
12. Individuals deprived of liberty or placed under legal guardianship,
13. Prior organ transplantation, including allogeneic stem cell transplantation,
14. Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver and inherited liver disease,
15. History of intra-abdominal inflammatory process within the last 12 months such as, but not limited to, diverticulitis, peptic ulcer disease or colitis.
16. 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.
17. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
18. Poorly controlled Type II diabetes mellitus defined as a screening fasting plasma glucose =160 mg/dL (or 8.8 mmol/L).
19. Severe infections within 2 weeks prior to inclusion, including but not limited to SARS-Cov-2 infection, hospitalization for complications of infection, bacteremia, or severe pneumonia.
20. Received therapeutic oral or IV antibiotics within 2 weeks prior to inclusion. Participants receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible.
21. Any contraindication to tumor biopsy,
22. Participant has spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease is clinically stable at least 14 daysprior to inclusion.
23. Administration of a live, attenuated vaccine within 4 weeks before the start of study medication or anticipation that such a liv
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method