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Exploratory Study of BO-112 in Adult Patients With Aggressive Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02828098
Recruitment Status : Terminated
First Posted : July 11, 2016
Last Update Posted : July 31, 2020
Sponsor:
Collaborator:
Pivotal S.L.
Information provided by (Responsible Party):
Highlight Therapeutics

Tracking Information
First Submitted Date  ICMJE June 23, 2016
First Posted Date  ICMJE July 11, 2016
Last Update Posted Date July 31, 2020
Study Start Date  ICMJE June 2016
Actual Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 12, 2017)
Number of subjects with adverse events [ Time Frame: 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
Original Primary Outcome Measures  ICMJE
 (submitted: July 6, 2016)
Number of subjects with adverse events [ Time Frame: Day 30 after administration of the last dose ]
To evaluate the safety and tolerability of B0-112 in terms of adverse events at every visit
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 12, 2017)
  • Circulating cytokines including type I IFNs, TNFalpha and IL6 (by ELISA) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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
Original Secondary Outcome Measures  ICMJE
 (submitted: July 6, 2016)
  • Circulating cytokines including type I IFNs, TNFalpha and IL6 (by ELISA) [ Time Frame: 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. ]
  • Plasma levels of BO-112 [ Time Frame: 0-15-30-240 minutes and 24 hours after administration of the drug ]
    To characterize the pharmacokinetics (PK) of BO-112 by measuring the amount in plasma at regular timepoints during the study
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Exploratory Study of BO-112 in Adult Patients With Aggressive Solid Tumors
Official Title  ICMJE An Exploratory First in Human Phase I Clinical and Pharmacokinetic Study of Intra-tumoral Administration of BO-112 in Adult Patients With Aggressive Solid Tumors, With an Extension Cohort in Combination With Anti-PD1 Treatment
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

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Cancer
Intervention  ICMJE
  • Drug: Part 1: BO-112
    Cohorts of three patients per dose level will be treated consecutively in the absence of Dose Limiting Toxicity (DLT).
  • Drug: Part 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.

    Other Name: anti-PD1 monoclonal antibody
Study Arms  ICMJE
  • Experimental: Part 1: BO-112 IT
    BO-112 dose 1 (starting dose) intratumoral injection. BO-112 dose 2, 3 and 4 are expected to be tested, upon confirmation of the safety profile of the starting dose.
    Intervention: Drug: Part 1: BO-112
  • Experimental: Part 2: BO-112 IT

    Combination treatment of BO-112 intratumoral injections with standard of care nivolumab intravenous treatment

    Or Combination treatment of BO-112 intratumoral injections with standard of care pembrolizumab intravenous treatment

    Intervention: Drug: Part 2: BO-112
Publications * Aznar MA, Planelles L, Perez-Olivares M, Molina C, Garasa S, Etxeberría I, Perez G, Rodriguez I, Bolaños E, Lopez-Casas P, Rodriguez-Ruiz ME, Perez-Gracia JL, Marquez-Rodas I, Teijeira A, Quintero M, Melero I. Immunotherapeutic effects of intratumoral nanoplexed poly I:C. J Immunother Cancer. 2019 May 2;7(1):116. doi: 10.1186/s40425-019-0568-2.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 30, 2020)
44
Original Estimated Enrollment  ICMJE
 (submitted: July 6, 2016)
24
Actual Study Completion Date  ICMJE July 2020
Actual Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 exclusion criteria for Part 2: Grade 3-4 toxicity due to anti-PD1 antibody or permanent discontinuation of anti-PD1 antibody due to immune related or other adverse reaction.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02828098
Other Study ID Numbers  ICMJE 112/2016-IT
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Highlight Therapeutics
Study Sponsor  ICMJE Highlight Therapeutics
Collaborators  ICMJE Pivotal S.L.
Investigators  ICMJE Not Provided
PRS Account Highlight Therapeutics
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP