Cancer
Conditions
Keywords
aggressive solid tumors
Brief summary
Part 1: 16 to 32 patients with aggressive solid tumors from whom biopsies can be obtained, will receive BO-112 through IT administration. Injected lesions must be palpable and biopsiable at the time of injection, and biopsied after 7-14 days. Patients will not receive an alternative therapy during the period comprising from first and second biopsy. BO-112 will be administered at a starting dose. Upon confirmation of the safety profile of the starting dose and evaluation of the pharmacokinetic (PK) profile, three additional dose levels are expected to be tested. During the course of the study, subjects will be examined for any side effects that may occur (safety and tolerability). Additionally this study will also study BO-112 biological activity, the innate and adaptive immune system response and signaling pathways, as well as signs of clinical relevance, will be studied. Part 2: An additional 30 patients with progressive disease while on anti-PD1 treatment for an approved indication, will receive BO-112 through IT administration in combination with the anti-PD1 treatment to evaluate the safety and tolerability of the combination. Injected lesions must be palpable and biopsiable at the time of injection. Patients will continue with their anti-PD1 treatment. During the course of the study, patients will be examined for any side effects that may occur (safety and tolerability). Additionally this part of the trial will also study BO-112 biological activity, the innate and adaptive immune system response and signaling pathways, as well as signs of clinical response
Interventions
DRUGPart 1: BO-112
Cohorts of three patients per dose level will be treated consecutively in the absence of Dose Limiting Toxicity (DLT).
DRUGPart 2: BO-112
BO-112 at a fixed dose will be administered as an intratumoral injection for up to 5 doses over 12 weeks and continue as long as there is benefit. Nivolumab will be administered as an intravenous infusion every 2 weeks at a dose of 3 mg/kg for up to a total period of one year. OR Pembrolizumab will be administered as an intravenous infusion every 3 weeks at either 200 mg or at 2 mg/kg depending on the indication, for up to a total period of one year.
Sponsors
Pivotal S.L.
Highlight Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients age 18 years or more on the day of signing informed consent form. 2. Histologically or cytologically confirmed aggressive solid tumors 3. Patients must have: * Biopsy-accessible tumors * No prior anticancer treatment during the last 14 days Additional inclusion criteria for Part 2: disease progression on treatment with anti-PD1 antibody for an approved indication
Exclusion criteria
Other relevant and clinically significant concomitant diseases or adverse clinical conditions which may jeopardize patient safety: * Increased cardiac risk: congestive heart failure; or unstable angina pectoris; or arrhythmia requiring treatment or uncontrolled arterial hypertension; or myocardial infarction within 12 months before inclusion in the study. * Patients with active central nervous system (CNS) lesions (including carcinomatous meningitis) will be excluded. However, patients will be eligible if: * All known CNS lesions have been treated with stereotactic therapy or surgery, AND * There has been no evidence of clinical and radiographic disease progression in the CNS for ≥ 4 weeks after radiotherapy or surgery, and has not required to increase in the last 4 weeks their steroids use or has not started a new course of steroids * Whole brain radiotherapy is not allowed, with the exception of patients who have had definitive resection or stereotactic therapy of all radiologically detectable parenchymal brain lesions. * Active infection. * Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic hepatitis B or C). * Any clinically significant abnormality on history or examination including diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication (physiologic doses of corticosteroids may be approved after consultation with the Sponsor). Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects with adverse events | Part 1: Day 30 after administration of the last dose. Part 2: 12 weeks and for patients who continue up to 1 year | To evaluate the safety and tolerability of B0-112 in terms of adverse events at every visit |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Circulating cytokines including type I IFNs, TNFalpha and IL6 (by ELISA) | Part 1: At three independent points during the study. Day 7-1 prior to administration, 24 hours after administration and 7-14 days after administration of the agent. Part 2: 12 weeks | — |
| Plasma levels of BO-112 | Part 1: 0-15-30-240 minutes and 24 hours after administration of the drug. Part 2: 1 day | To characterize the pharmacokinetics (PK) of BO-112 by measuring the amount in plasma at regular timepoints during the study |
| Anti-tumor activity | 12 weeks and for patients who continue up to 1 year | Part 2 only: To evaluate the antitumor activity of the combination of BO-112 and anti-PD1 treatment |
Countries
Spain
Outcome results
None listed