LUMINOS-101: Lerapolturev (PVSRIPO) and Pembrolizumab in Patients With Recurrent Glioblastoma

NCT04479241 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: LUMINOS-101
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 10

Brief Summary

This Phase 2 single arm trial in patients with rGBM will characterize the efficacy, safety, tolerability and initial efficacy of lerapolturev intratumoral infusion followed by intravenous pembrolizumab 14 to 28 days later, and every 3 weeks, thereafter.

Conditions

Glioblastoma; Recurrent Glioblastoma; Supratentorial Glioblastoma; Brain Tumor

Outcome Measures

Primary Outcomes (4)

• Objective Response Rate (ORR)

  Objective response rate (comprised of patients meeting an objective radiographic response or ORR): Patients achieving a complete response (CR) or partial response (PR).

  24 months

• Frequency and Severity of Treatment-emergent Adverse Events

  Count of participants experiencing a treatment-emergent adverse event is reported here. Detailed frequency and severity data are reported in the Adverse Event table.

  Up to 30 days after discontinuation of pembrolizumab

• Duration of Response (DOR)

  DOR: Time from first ORR observed (once confirmed) until PD first observed (once confirmed) or death; whichever comes first.

  24 months

• Durable Radiographic Response (DRR)

  DRR: An ORR that persists for ≥ 6 months.

  24 months

Secondary Outcomes (2)

• Disease Control Rate (DCR)

  24 months

• Survival Assessed by Kaplan-Meier Methods

  24 months

Study Arms (1)

lerapolturev + pembrolizumab

EXPERIMENTAL

Lerapolturev delivered once intratumorally via convection enhanced delivery. Pembrolizumab given intravenously every 3 weeks.

Biological: lerapolturev; Biological: pembrolizumab

Interventions

lerapolturev BIOLOGICAL

Lerapolturev (5x10\^7 TCID50) delivered intratumorally via convection enhanced delivery (CED).

lerapolturev + pembrolizumab

pembrolizumab BIOLOGICAL

Pembrolizumab (200 mg IV) given every 3 weeks.

lerapolturev + pembrolizumab

Eligibility Criteria

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

You may qualify if:

• ≥ 18 years of age.
• Recurrent supratentorial glioblastoma (GBM) confirmed via prior histology by the site's neuropathologist or designate.
• Histologically confirmed recurrent glioblastoma (rGBM) within 6 weeks of Lerapolturev infusion will not require a biopsy to confirm active tumor prior to catheter placement
• Progression of primary glioblastoma or transformation from a lower grade to a higher grade is acceptable for recurrence and as for primary glioblastoma, must be confirmed via prior histology by site pathologist
• Enhancing lesion ≥1 cm shortest diameter to ≤ 5.5 cm longest diameter in all planes.
• Before catheter placement based on screening MRI and at the time of catheter placement via CT prior to infusion, neurosurgical investigator must confirm placement of infusion catheter within or through the progressive enhancing tumor is feasible and at a safe distance relative to eloquent brain function, with the tip of the catheter being placed:
• Within the enhancing portion or in the vicinity of enhancement of target lesion (ie, infiltrative disease).
• ≥ 0.5 cm from ventricles.
• ≥ 1 cm deep into the brain.
• ≥ 0.5 cm from corpus callosum.
• First or second relapse supported by MRI or CT scan; relapse is defined as progression following initial/prior therapy(ies).
• Failed previous first line therapy: maximum surgical resection and radiotherapy (RT) (plus concomitant chemotherapy followed by maintenance chemotherapy if unknown or methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter). Patients who begin but do not complete chemotherapy/RT may still be considered for eligibility at the discretion of Sponsor.
• Karnofsky Performance Status ≥ 70 at screening and baseline.
• Undergone prior vaccination against PV and received a boost immunization with trivalent inactivated poliovirus vaccine (IPOL®) at least 1 week, but less than 6 weeks, prior to administration of Lerapolturev. Note: Patients who are unsure of their prior vaccination status/who have not been vaccinated must provide proof of vaccination and/or evidence of anti-PV immunity prior to enrollment, as applicable.
• Ability to safely discontinue anti-coagulant therapy(ies) prior to biopsy/catheter placement, as required per site/surgical guidelines.

You may not qualify if:

• Received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti- CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) ≤ 12 weeks prior to lerapolturev infusion (Note: does not apply for patients treated with pembrolizumab under this protocol who are eligible for lerapolturev retreatment). Note: patients who had previously permanently discontinued any anti-PD-1 or PD-L1 therapy due to severe or life-threatening immune-related adverse events are excluded.
• Excluded are:
• Neoplastic lesions in the brainstem, cerebellum, or spinal cord.
• Radiological evidence of active/growing multifocal disease: no size increase \> 0.5 cm in any direction of any other enhancing non-target lesions present at baseline confirmed via most recent, prior, consecutive MRIs at least 3 months apart.
• Tumors with ≥ 1cm of contrast-enhancing tumor component crossing the midline (crossing the corpus callosum).
• Extensive subependymal disease: multiple lesions or lesions covering \> 50% of subependymal space. Tumor touching subependymal space allowed.
• Extensive leptomeningeal disease: multiple lesions or lesions covering \> 50% of leptomeninges. Tumor touching leptomeninges allowed.
• Has received systemic immunosuppressive treatments other than systemic corticosteroids (eg, methotrexate, chloroquine, azathioprine) within six months of Lerapolturev infusion.
• Requires treatment with high dose systemic corticosteroids, defined as dexamethasone \> 4 mg/day or equivalent, within 2 weeks of Lerapolturev infusion.
• Prior interstitial brachytherapy, implanted chemotherapy, stereotactic radiosurgery or therapeutics delivered by local injection or CED, including Lerapolturev (except for qualifying patients being retreated with Lerapolturev within this trial).
• Pregnant and/or breast feeding female; patient/female partner of childbearing potential who is unwilling to utilize protocol-defined acceptable form of contraception for duration of study.
• Impending/life-threatening cerebral herniation syndrome, per neurosurgeon/designate.
• Severe, active co-morbidity, defined as follows:
• Infection requiring IV treatment/unexplained febrile illness (Tmax \> 99.5°F/37.5°C)
• Known immunosuppressive disease/human immunodeficiency virus infection

Sponsors & Collaborators

• Istari Oncology, Inc.: lead

Study Sites (10)

University of California San Francisco

San Francisco, California, 94143, United States

Location

UConn Health

Farmington, Connecticut, 06030, United States

Location

Baptist MD Anderson Cancer Center

Jacksonville, Florida, 32207, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Head of Clinical Operations
• Organization: Istari Oncology

info@istarioncology.com

919-245-7662

Study Officials

• Lisa Franklin

  Istari Oncology

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2020
• First Posted: July 21, 2020
• Study Start: October 21, 2020
• Primary Completion: June 5, 2024
• Study Completion: June 21, 2024
• Last Updated: June 5, 2025
• Results First Posted: March 25, 2025

Record last verified: 2025-04

Locations

US (10)