Study of BO-112 With Radiotherapy and Nivolumab for Metastatic Refractory NSCLC

NCT05265650 | Unknown Phase 1 DMC

• 1 other identifier: BORT-112
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a study of repeated IT administrations of BO-112 in combination with ablative radiotherapy (SABR) and concurrent nivolumab in patients with metastatic PD-1/PD-L1-refractory NSCLC.

Conditions

Non-Small Cell Lung Cancer Metastatic

Keywords

BO112; Intratumoral; Immunotherapy; NSCLC

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse events and Serious Adverse Events

  Number and proportion of subjects with TEAEs with severity ≥ Grade 3 (NCI-CTCAE v. 5.0)

  Throughout study completion, an average of 1 year

Secondary Outcomes (4)

• Number and Proportion of Subjects with TEAEs Grade ≥3

  Throughout study completion, an average of 1 year

• Efficacy: Progression-free survival (PFS)

  Throughout study completion, an average of 1 year

• Efficacy: ORR, DCR

  Throughout study completion, an average of 1 year

• Tolerability: study discontinuations

  Throughout study completion, an average of 1 year

Study Arms (1)

Single Treatment Arm

EXPERIMENTAL

Treatment will consist of IT administrations of BO-112 in combination with ablative radiotherapy (SABR) and concurrent with systemic administration of nivolumab in patients with metastatic PD-1/PD-L1-refractory NSCLC. In the initial cohort A, BO-112 will be IT injected on a weekly basis during the first cycle on the accessible lesions, and every 2 weeks thereafter. The minimum dose to be injected per visit is 1 mg (unless injected lesion in case of response, if solitary, becomes smaller than 1.5 cm) and the maximum dose is 2 mg (3.4 mL), distributed in the different lesions. Stereotactic ablative radiotherapy (SABR) will be initiated on week 3. In the cohort B, BO-112 and SABR will be administered as described previously. Nivolumab will be administered at the dose of 240 mg every 2 weeks in both cohorts, starting at cycle 4 (week 7) in cohort A and at cycle 3 (week 5) in cohort B.

Drug: BO-112 in combination with ablative radiotherapy (SABR) and nivolumab; Procedure: Tissue Biopsies

Interventions

BO-112 in combination with ablative radiotherapy (SABR) and nivolumab DRUG

Study treatment will consist of BO-112 IT injections in combination with IV nivolumab infusions and SABR to accessible metastases.

Also known as: BO-112 with radiotherapy and nivolumab

Single Treatment Arm

Tissue Biopsies PROCEDURE

Four research biopsies will be taken from accessible injected lesions, at the time of the IT injection of BO-112.

Single Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent
• ≥18 years of age
• Diagnosis of histologically confirmed metastatic NSCLC (histologic confirmation of a NSCLC tumor is acceptable if accompanied by radiographic evidence of metastatic disease).
• At least 1 accessible metastasis of minimum 20 mm in diameter that is suitable for percutaneous IT injection of BO-112. For liver metastasis IT injection, the lesion to be treated cannot infiltrate the main hepatic vessels (including, but not limited to, absence of tumor infiltration into the main portal vein, hepatic vein, or vena cava) and must be amenable to be biopsied. The irradiated and injected site must be accessible to tumor biopsy.
• Presence of at least 1 measurable lesion according to RECIST v. 1.1. Note: this may be the metastasis selected for injection if it is the only measurable lesion present.
• Prior resection of metastatic disease is allowed if completed more than 6 months previous to study enrollment and at the time of study entry there is progressive disease.
• Patients must be refractory to anti-PD-1, or anti-PD-L1 inhibitors. Subjects who have received prior anti-PD-1/PD-L1 therapies must have received at least 4 months of treatment. Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided at least 2.5 half-lives (30 days) have elapsed from the last dose of anti-CTLA-4 to the first dose of nivolumab and there was no history of severe immune-mediated adverse effects from anti-CTLA-4 (NCI CTCAE Grade 3 and 4). Subjects with EGFR or ALK genomic tumor aberrations with progression on approved therapy for these aberrations are eligible.
• Participant must be candidate for SABR to at least 1 lesion with no more than 5 irradiated metastases in total. Maximum of 3 metastases to be irradiated in any one organ are allowed.
• Evaluation by a radiation oncologist within 21 days prior to study registration, including imaging workup to document metastases.
• Irradiation by SABR should not include metastases located within 3 cm of the previously irradiated structures:
• Spinal cord previously irradiated to \>40 Gy.
• Brachial plexus previously irradiated to \>50 Gy.
• Small intestine, large intestine, or stomach previously irradiated to \>45 Gy.
• Brainstem previously irradiated to \>50 Gy.
• Lung previously irradiated with prior V20 Gy \>30%.

You may not qualify if:

• Subjects are excluded from the study if any of the following criteria apply:
• Prior treatment with any Toll-like receptor (TLR) agonist or sting agonist.
• Chemotherapy, definitive (curative) radiation, or biological cancer therapy within 4 weeks prior to the first dose of study treatment. Note: Participants must have recovered from all adverse events (AEs) due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible. If the participants received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Palliative radiotherapy (≤2 weeks of radiotherapy) within 1 week of start of study treatment. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases. Patients with a history of treated CNS metastases are eligible, providing all of the following criteria are met:
• Measurable disease, per RECIST v. 1.1, must be present outside the CNS.
• The patient has no history of intracranial hemorrhage or spinal cord hemorrhage.
• Metastases are limited to the cerebellum or the supratentorial region (i.e., no metastases to the midbrain, pons, medulla, or spinal cord).
• There is no evidence of interim radiological progression for at least 4 weeks between completion of CNS-directed therapy and the screening brain scan.
• The patient has clinical stability from the neurological point of view and doesn´t require corticosteroids as therapy for CNS disease for at least 14 days. Anti-convulsant therapy at a stable dose is permitted.
• History of leptomeningeal disease.
• History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
• Life expectancy of \<12 weeks.
• Active infection requiring systemic therapy within 1 week of start of study treatment.
• Serious medical comorbidities precluding radiotherapy. These include, but are not limited to, the following:

Sponsors & Collaborators

• Clinica Universidad de Navarra, Universidad de Navarra: lead
• Highlight Therapeutics: collaborator

Study Sites (1)

Clínica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

RECRUITING

MeSH Terms

Interventions

BO-112; Radiosurgery; Nivolumab; Radiotherapy

Intervention Hierarchy (Ancestors)

Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Maria E Rodriguez, PhD

  Clinica Universidad de Navarra

  PRINCIPAL INVESTIGATOR

Central Study Contacts

María E Rodríguez Ruiz

CONTACT

948255400; mrruiz@unav.es

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phase Ib/II study with one single treatment arm (BO-112 in combination with SABR and nivolumab)

Study Record Dates

• First Submitted: February 22, 2022
• First Posted: March 3, 2022
• Study Start: June 13, 2022
• Primary Completion: March 1, 2024
• Study Completion: June 1, 2024
• Last Updated: July 19, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)