Clinical study of intratumoral administration of BO-112 combined with radiotherapy and nivolumab in patients with metastatic resistant non-small cell lung cancer
- Conditions
- Metastatic PD-1/PDL-1 refractory non-small-cell lung cancerMedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA 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: 20.0Level: HLGTClassification code 10038666Term: Respiratory and mediastinal neoplasms malignant and unspecifiedSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: HLTClassification code 10029664Term: Non-small cell neoplasms malignant of the respiratory tract cell type specifiedSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-006410-36-ES
- Lead Sponsor
- Clínica Universidad Navarra
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 30
- Willing and able to give written informed consent for the study
- =18 years of age
- Diagnosis of histologically confirmed metastatic NSCLC
- Participant must have either recurrence after, or progression on or lack of response to established standard of care anticancer therapies (including platine treatment) in the recurrent setting or subject refuses such available therapy.
- At least one accessible metastasis of minimum 20 mm in diameter that is suitable for percutaneous IT injection of BO-112. The irradiated and injected site must be accessible to tumor biopsy
- At least one measurable lesion according to RECIST v. 1.1
- Prior resection of metastatic disease is allowed if completed more than 6 months previous to study enrollment and at the time of study entry there is progressive disease
- Patients must be refractory to anti-PD-1, or anti-PD-L1 inhibitors in any prior treatment line
- Participant must be candidate for SABR to at least one lesion with no more than five irradiated metastases in total. Maximum of three metastases in any one organ are allowed
- Evaluation by a radiation oncologist within 21 days prior to study registration, including imaging workup to document metastases.
- Irradiation by SABR should not include metastases located within 3 cm of the previously irradiated structures:
• Spinal cord previously irradiated to >40 Gy
• Brachial plexus previously irradiated to >50 Gy.
• Small intestine, large intestine, or stomach previously irradiated to >45 Gy.
• Brainstem previously irradiated to >50 Gy.
• Lung previously irradiated with prior V20 Gy >30%.
- ECOG performance status of 0 or 1
- Adequate hematologic and end-organ function defined by the following laboratory results obtained at screening and Visit 1 prior to the first dose of study treatment:
• ANC =1.5 × 109/L.
• Platelet count =100 × 109/L.
• Hemoglobin =9.0 g/dL.
• AST and ALT =2.5x ULN (5 × ULN if presence of liver metastases).
• Serum total bilirubin <2 × ULN (if known Gilbert’s syndrome, serum bilirubin level <3 × ULN).
• Prothrombin time (PT) (or international normalized ratio [INR]) within normal limits and activated partial prothrombin time (aPTT) within normal limits
• Serum creatinine <1.5 × ULN or creatinine clearance =30 mL/min (Cockroft-Gault formula).
- Female participants of childbearing potential: negative urine or serum pregnancy test within 10 days of initiating study treatment.
- Female participants of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 6 months after the last dose of study medication.
- Male participant should agree to use an adequate method of contraception and refrain from sperm donation starting with the first dose of study therapy through 6 months after the last dose of study therapy.
- HIV infected participants must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease defined as:
•Participants on ART must have a CD4+ T-cell count >350 cells/mm3 at time of screening.
•Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification for at least 12 weeks prior to screening
•Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to study entry (Day 1).
•Participants who are HBsAg positive
- Prior treatment with any Toll-like receptor agonist or sting agonist
- Chemotherapy, definitive (curative) radiation, or biological cancer therapy within 4 weeks prior to the first dose of study treatment
- Palliative radiotherapy (= 2 weeks of radiotherapy) within 1 week of start of study treatment
- Symptomatic, untreated, or actively progressing central nervous system metastases. Patients with a history of treated CNS metastases are eligible, provided that all of the following criteria are met:
*Measurable disease, per RECIST v1.1, must be present outside the CNS
*Patient has no history of intracranial hemorrhage or spinal cord hemorrhage
*Metastases are limited to the cerebellum or the supratentorial region
*No evidence of interim radiological progression for at least 4 weeks between completion of CNS-directed therapy and the screening brain scan
*Patient has clinical stability from the neurological point of view and doesn´t require corticosteroids as therapy for CNS disease for at least 14 day. Anti-convulsant therapy at a stable dose is permitted
- History of leptomeningeal disease.
- History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
- Life expectancy <12 weeks.
- Active infection requiring systemic therapy within 1 week of start of study treatment
- Serious medical comorbidities precluding radiotherapy, including but not limited to:
*Interstitial lung disease in patients requiring thoracic radiation
*Crohn’s disease in patients where the GI tract will receive radiotherapy, or ulcerative colitis where the bowel will receive radiotherapy
* Connective tissue disorders such as lupus or scleroderma
* Known genetic disorders associated with increased toxicity to radiation therapy
- For patients with liver metastases:
*Moderate/severe liver dysfunction (Child Pugh B or C).
*Liver metastasis(es) with macroscopic tumor infiltration into the main portal vein, hepatic vein, or vena cava.
- Substantial overlap with a previously treated radiation volume:
*Prior radiotherapy in general is allowed, as long as the composite plan meets dose constraints herein.
*For patients treated with radiation previously, biological effective dose calculations should be used to equate previous doses to the tolerance doses listed in the technical radiotherapy manual
*Lesions that have been treated with radiotherapy within the last 6 months should not be radiated
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
- Active autoimmune disease that required systemic treatment in past 2 years. Replacement therapy is not considered a form of systemic treatment and is allowed
- Receiving systemic immunosuppressive therapy within 28 days before enrolment with the exceptions of intranasal, topical, and inhaled corticosteroids or oral corticosteroids at physiological doses not exceeding 10 mg/day of prednisone or equivalent
- HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease
- For WOCBP: pregnancy or a positive urine pregnancy test (eg within 72 hours) prior to treatment; or breastfeeding
- Any other medical condition which would impact the safety of
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Safety of repeated IT administrations of BO-112 in metastatic lesions in combination with IV nivolumab and radiotherapy.;Secondary Objective: - Further characterization of safety and of clinical activity of the combination as well as determination of systemic exposure of BO 112 and radiotherapy.<br>- Evaluation of antitumoral and immunological effects in the TME of the treated and un-treated lesion.<br>- Evaluate preliminary efficacy as defined by tumor response rate of the treated and non-treated lesion(s). To assess imaging response biomarkers.;Primary end point(s): Safety: number and proportion of subjects with study treatment-related TEAEs with severity = Grade 3 (NCI-CTCAE v 5.0) in the global population;Timepoint(s) of evaluation of this end point: In all study visits
- Secondary Outcome Measures
Name Time Method