Clinical trial NCT02828098: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: aggressive solid tumors
Lead sponsor: Highlight Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Pivotal S.L.
First posted: 2016-07-11
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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


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.

Primary outcomes:
measure: Number of subjects with adverse events
timeFrame: Part 1: Day 30 after administration of the last dose. Part 2: 12 weeks and for patients who continue up to 1 year
Secondary outcomes:
measure: Circulating cytokines including type I IFNs, TNFalpha and IL6 (by ELISA)
timeFrame: 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
measure: Plasma levels of BO-112
timeFrame: Part 1: 0-15-30-240 minutes and 24 hours after administration of the drug. Part 2: 1 day
measure: Anti-tumor activity
timeFrame: 12 weeks and for patients who continue up to 1 year
Other outcomes:
Locations:
city: Pamplona
country: Spain
facility: Clínica Universitaria Navarra
state: Navarra
city: Barcelona
country: Spain
facility: ICO Hospital Duran i Reynals
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Quiron Madrid
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
Study officials:
References:
citation: 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.