Metastatic PD-1/PDL-1 refractory non-small-cell lung cancer MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: SOC Classification code 10029104 Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps) System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA vers
Conditions
Interventions
Product Name: BO-112
Product Code: BO-112
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Not available
CAS Number: 42424-50-0
Current Sponsor code: BO-112
Other descriptive name: P
Sponsors
Clínica Universidad Navarra
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - 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 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
Exclusion criteria
Exclusion criteria: - 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. - Evaluation of antitumoral and immunological effects in the TME of the treated and un-treated lesion. - 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
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Safety: number and proportion of subjects with study treatment-related TEAEs Grade =3 (NCI-CTCAE v. 5.0) evaluated by separate in the safety run-in cohorts. • Safety: number and proportion of subjects with TEAEs (any grade) in the global population and by cohorts. • Safety: number and proportion of subjects with related TEAEs (any grade). • Efficacy: progression-free survival (PFS), defined as the time from C1D1 to the first occurrence of disease progression or death from any cause (whichever occurs first) as determined by the investigator according to RECIST v. 1.1, in ITT population. • Tolerability: number of study discontinuations due to related TEAE. • Efficacy: PFS in ITT population based on iRECIST. • Efficacy: ORR based on the best overall response (BOR) using RECIST v. 1.1 in ITT population. • Efficacy: disease control rate (DCR = CR, PR and SD of at least 12 weeks duration) on the global tumor assessment by RECIST v. 1.1 in ITT population. • Efficacy: DCR = iCR, iPR + iSD of at least 12 weeks duration) using iRECIST in ITT population. • Efficacy: overall survival rate at 6 and 12 months;Timepoint(s) of evaluation of this end point: Several timepoints throughout the study and at the end of the study. | — |
Countries
Spain
Contacts
Public ContactClinical Research Information
HealthCo Trials, S.L.
Outcome results
None listed