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

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

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

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Drug: Part 1: BO-112; Drug: Part 2: BO-112

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08908
    • ICO Hospital Duran i Reynals
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de octubre
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon
  • Madrid, Spain, 28223
    • Hospital Universitario Quiron Madrid
  • Malaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clínica Universitaria Navarra

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: Part 1: BO-112; Cohorts of three patients per dose level will be treated consecutively in the absence of Dose Limiting Toxicity (DLT).
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	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 Names: anti-PD1 monoclonal antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with adverse events	To evaluate the safety and tolerability of B0-112 in terms of adverse events at every visit	Part 1: Day 30 after administration of the last dose. Part 2: 12 weeks and for patients who continue up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	To characterize the pharmacokinetics (PK) of BO-112 by measuring the amount in plasma at regular timepoints during the study	Part 1: 0-15-30-240 minutes and 24 hours after administration of the drug. Part 2: 1 day
Anti-tumor activity	Part 2 only: To evaluate the antitumor activity of the combination of BO-112 and anti-PD1 treatment	12 weeks and for patients who continue up to 1 year

Collaborators and Investigators

• Sponsor: Highlight Therapeutics
• Collaborators: Pivotal S.L.

Publications and helpful links

General Publications

• Aznar MA, Planelles L, Perez-Olivares M, Molina C, Garasa S, Etxeberria I, Perez G, Rodriguez I, Bolanos 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Actual): July 1, 2020
• Study Completion (Actual): July 1, 2020

Study Registration Dates

• First Submitted: June 23, 2016
• First Submitted That Met QC Criteria: July 6, 2016
• First Posted (Estimated): July 11, 2016

Study Record Updates

• Last Update Posted (Estimated): January 29, 2024
• Last Update Submitted That Met QC Criteria: January 26, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: aggressive solid tumors
• Additional Relevant MeSH Terms: Behavioral Symptoms; Aggression
• Other Study ID Numbers: 112/2016-IT