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

NCT ID: NCT02828098

Last Updated: 2024-01-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2020-07-31

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

Conditions

Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Part 1: BO-112

Intervention Type: DRUG

Cohorts of three patients per dose level will be treated consecutively in the absence of Dose Limiting Toxicity (DLT).

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

Group Type: EXPERIMENTAL

Part 2: BO-112

Intervention Type: DRUG

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.

Interventions

Part 1: BO-112

Cohorts of three patients per dose level will be treated consecutively in the absence of Dose Limiting Toxicity (DLT).

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

anti-PD1 monoclonal antibody

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

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pivotal S.L.

INDUSTRY

Sponsor Role: collaborator

Highlight Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Clínica Universitaria Navarra

Pamplona, Navarre, Spain

ICO Hospital Duran i Reynals

Barcelona, , Spain

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario Quiron Madrid

Madrid, , Spain

Hospital Universitario Virgen de la Victoria

Málaga, , Spain

Countries

Spain

References

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.

Reference Type: DERIVED

PMID: 31046839 (View on PubMed)

Other Identifiers

112/2016-IT

Identifier Type: -

Identifier Source: org_study_id