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

• ClinicalTrials.gov Identifier: NCT02828098
• Recruitment Status: Terminated
• First Posted: July 11, 2016
• Last Update Posted: July 31, 2020
• Sponsor: Highlight Therapeutics
• Collaborator: Pivotal S.L.
• Information provided by (Responsible Party): Highlight Therapeutics

Tracking Information

• First Submitted Date: June 23, 2016
• First Posted Date: July 11, 2016
• Last Update Posted Date: July 31, 2020
• Study Start Date: June 2016
• Actual Primary Completion Date: July 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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

Current Secondary Outcome Measures (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 (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: Exploratory Study of BO-112 in Adult Patients With Aggressive Solid Tumors
• Official Title: 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: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Other
• Condition: Cancer

Intervention

• 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

• 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: July 30, 2020): 44
• Original Estimated Enrollment (submitted: July 6, 2016): 24
• Actual Study Completion Date: July 2020
• Actual Primary Completion Date: July 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT02828098
• Other Study ID Numbers: 112/2016-IT
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Highlight Therapeutics
• Study Sponsor: Highlight Therapeutics
• Collaborators: Pivotal S.L.
• Investigators: Not Provided
• PRS Account: Highlight Therapeutics
• Verification Date: July 2020