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

Primary Purpose

Cancer

Status

Terminated

Phase

Phase 1

Locations

Spain

Study Type

Interventional

Intervention

Part 1: BO-112

Part 2: BO-112

About this trial

This is an interventional other trial for Cancer focused on measuring aggressive solid tumors

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients age 18 years or more on the day of signing informed consent form.
Histologically or cytologically confirmed aggressive solid tumors
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.

Sites / Locations

Clínica Universitaria Navarra
ICO Hospital Duran i Reynals
Hospital General Universitario Gregorio Marañón
Hospital Universitario Ramon y Cajal
Hospital Universitario 12 de Octubre
Hospital Universitario Quiron Madrid
Hospital Universitario Virgen de la Victoria

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Part 1: BO-112 IT

Part 2: BO-112 IT

Arm Description

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.

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

Outcomes

Primary Outcome Measures

Number of subjects with adverse events

To evaluate the safety and tolerability of B0-112 in terms of adverse events at every visit

Secondary Outcome Measures

Circulating cytokines including type I IFNs, TNFalpha and IL6 (by ELISA)

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

Anti-tumor activity

Part 2 only: To evaluate the antitumor activity of the combination of BO-112 and anti-PD1 treatment

Full Information

NCT ID

NCT02828098

First Posted

June 23, 2016

Last Updated

July 30, 2020

Sponsor

Highlight Therapeutics

Collaborators

Pivotal S.L.

1. Study Identification

Unique Protocol Identification Number

NCT02828098

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Terminated

Study Start Date

June 2016 (undefined)

Primary Completion Date

July 2020 (Actual)

Study Completion Date

July 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Highlight Therapeutics

Collaborators

Pivotal S.L.

4. Oversight

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cancer

Keywords

aggressive solid tumors

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

44 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1: BO-112 IT

Arm Type

Experimental

Arm Description

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.

Arm Title

Part 2: BO-112 IT

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Part 1: BO-112

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Part 2: BO-112

Other Intervention Name(s)

anti-PD1 monoclonal antibody

Intervention Description

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.

Primary Outcome Measure Information:

Title

Number of subjects with adverse events

Description

To evaluate the safety and tolerability of B0-112 in terms of adverse events at every visit

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

Secondary Outcome Measure Information:

Title

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

Title

Plasma levels of BO-112

Description

To characterize the pharmacokinetics (PK) of BO-112 by measuring the amount in plasma at regular timepoints during the study

Time Frame

Part 1: 0-15-30-240 minutes and 24 hours after administration of the drug. Part 2: 1 day

Title

Anti-tumor activity

Description

Part 2 only: To evaluate the antitumor activity of the combination of BO-112 and anti-PD1 treatment

Time Frame

12 weeks and for patients who continue up to 1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients age 18 years or more on the day of signing informed consent form. Histologically or cytologically confirmed aggressive solid tumors 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.

Facility Information:

Facility Name

Clínica Universitaria Navarra

City

Pamplona

State/Province

Navarra

ZIP/Postal Code

31008

Country

Spain

Facility Name

ICO Hospital Duran i Reynals

City

Barcelona

ZIP/Postal Code

08908

Country

Spain

Facility Name

Hospital General Universitario Gregorio Marañón

City

Madrid

ZIP/Postal Code

28007

Country

Spain

Facility Name

Hospital Universitario Ramon y Cajal

City

Madrid

ZIP/Postal Code

28034

Country

Spain

Facility Name

Hospital Universitario 12 de Octubre

City

Madrid

ZIP/Postal Code

28041

Country

Spain

Facility Name

Hospital Universitario Quiron Madrid

City

Madrid

ZIP/Postal Code

28223

Country

Spain

Facility Name

Hospital Universitario Virgen de la Victoria

City

Malaga

ZIP/Postal Code

29010

Country

Spain

12. IPD Sharing Statement

Citations:

PubMed Identifier

31046839

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.

Results Reference

derived

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

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