GlioblastomaPhase 2NCT04479241
LUMINOS-101: Lerapolturev (PVSRIPO) and Pembrolizumab in Patients With Recurrent Glioblastoma
A Phase 2 study testing lerapolturev and pembrolizumab in people with Glioblastoma and Recurrent Glioblastoma, run by Istari Oncology, Inc. at 10 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Recurrent Glioblastoma, Supratentorial Glioblastoma
- What is being tested?
- lerapolturev and pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 10 sitesUnited States
- Study dates
- 21 Oct 2020to 21 Jun 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥ 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:
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- 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.
- Hemoglobin ≥ 9 g/dL prior to biopsy/catheter placement.
- Platelet count ≥ 100,000/μL (unsupported); ≥ 125,000/ μL (can be supported via platelet transfusion) at biopsy/catheter placement.
- Absolute Neutrophil Count (ANC) ≥ 1000/μL prior to biopsy/catheter placement.
- Creatinine ≤ 1.2 x Upper Limit of Normal (ULN) prior to biopsy/catheter placement.
- Total bilirubin, Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) ≤ 2.5 x ULN prior to biopsy/catheter placement.
- Prothrombin time (PT) and activated Partial Thromboplastin Time (aPTT) ≤ 1.2 x ULN prior to biopsy/catheter placement.
- If undetectable antitetanus toxin (ATT) Immunoglobulin G (IgG) at screen, Tdap booster vaccine ≥ 1 week prior to biopsy/catheter placement.
- Patients must be willing and able to understand and provide written informed consent.
Who cannot join
- 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.
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- 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
- Known active hepatitis B or C infection via positive viral DNA or RNA, respectively
- Unstable or severe intercurrent medical conditions such as severe heart disease (New York Heart Association Class 3 or 4)
- Known lung disease with forced expiratory volume in 1st second of expiration < 50%
- Uncontrolled diabetes mellitus (eg, hemoglobin A1C level > 7.0% with treatment)
- History of other malignancy requiring active treatment within 2 years of biopsy/catheter placement with the exception of those with a negligible risk of metastasis or death (eg, resected cutaneous basal cell carcinoma, or other cancers with 5-year overall survival (OS) of >90%)
- Known albumin allergy.
- Uncontrolled unexplained bleeding and/or hemoptysis within 4 weeks of planned lerapolturev infusion.
- Inability to undergo brain MRI with and without contrast. History of severe/anaphylactic reaction to gadolinium contrast agent is excluded. Mild allergy (eg, rash) acceptable with prophylactic acetaminophen and diphenhydramine.
- History of neurological complications due to PV infection.
- Not recovered from toxic side effects (alopecia acceptable) and/or no current or prior tumor treatments within the following timeframe relative to biopsy/catheter placement:
- Chemotherapy or bevacizumab ≤ 4 weeks (except for nitrosourea (6 weeks) or metronomic dosed chemotherapy/targeted therapies such as daily temozolomide, etoposide or cyclophosphamide (1 week)).
- Tumor treating fields ≤ 7 days.
- RT of brain ≤ 12 weeks, except for progressive disease outside of the radiation field or 2 progressive scans at least 4 weeks apart or histopathologic confirmation.
- History of agammaglobulinemia.
- Known hypersensitivity to pembrolizumab, or any components of pembrolizumab.
- Active autoimmune disease requiring systemic immunomodulatory treatment within the past 12 months; physiologic replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
- History of other malignancy requiring active treatment within 2 years of biopsy/catheter placement with the exception of those with a negligible risk of metastasis or death (eg, resected cutaneous basal cell carcinoma, or other cancers with 5-year OS of >90%)
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
The Ohio State University
Columbus, Ohio, 43210
Duke University Medical Center
Durham, North Carolina, 27710
UConn Health
Farmington, Connecticut, 06030
Baptist MD Anderson Cancer Center
Jacksonville, Florida, 32207
Oregon Health and Science University
Portland, Oregon, 97239
University of California San Francisco
San Francisco, California, 94143
About this study
Official title: A Phase 2, Open-label, Single-arm Study Evaluating the Efficacy, Safety and Tolerability of Lerapolturev (PVSRIPO) and the Immune Checkpoint Inhibitor Pembrolizumab in the Treatment of Patients With Recurrent Glioblastoma
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.
- Being tested
- lerapolturev, pembrolizumab
- Medical subject headings
- Glioblastoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lerapolturevBiological
Lerapolturev (5x10^7 TCID50) delivered intratumorally via convection enhanced delivery (CED).
pembrolizumabBiological
Pembrolizumab (200 mg IV) given every 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| lerapolturev + pembrolizumab | Experimental | Lerapolturev delivered once intratumorally via convection enhanced delivery. Pembrolizumab given intravenously every 3 weeks. Receives: Biological: lerapolturev; Biological: pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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.
Measured: 24 months
Durable Radiographic Response (DRR)
DRR: An ORR that persists for ≥ 6 months.
Measured: 24 months
Secondary outcomes (2)
Disease Control Rate (DCR)
Proportion of patients achieving stable disease (SD), CR or PR via protocol-specified response criteria
Measured: 24 months
Survival Assessed by Kaplan-Meier Methods
Overall survival (months) post-lerapolturev infusion estimated by Kaplan-Meier methods.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2020
- Study start21 Oct 2020
- Primary completion5 Jun 2024
- Study completion21 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istari Oncology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lisa Franklin, Study director, Istari Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04479241
- Sponsor's protocol ID
- LUMINOS-101
- Status last verified
- Apr 2025
- First submitted
- 16 Jul 2020
- Last updated
- 5 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Open-label, Single-arm Study Evaluating the Efficacy, Safety and Tolerability of Lerapolturev (PVSRIPO) and the Immune Checkpoint Inhibitor Pembrolizumab in the Treatment of Patients With Recurrent Glioblastoma
- ClinicalTrials.gov ID
- NCT04479241
- Acronym / sponsor ID
- LUMINOS-101
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Istari Oncology, Inc.Industry (pharma, biotech, devices)
- Study start
- 21 Oct 2020 (actual)
- Primary completion
- 5 Jun 2024 (actual)
- Study completion
- 21 Jun 2024 (actual)
- First posted
- 21 Jul 2020 (actual)
- Results
- Posted 25 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| lerapolturev + pembrolizumab | Experimental | Biological: lerapolturev, Biological: pembrolizumabLerapolturev delivered once intratumorally via convection enhanced delivery. Pembrolizumab given intravenously every 3 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- ≥ 18 years of age.
- Recurrent supratentorial glioblastoma (GBM) confirmed via prior histology by the site's neuropathologist or designate.
- 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:
- First or second relapse supported by MRI or CT scan; relapse is defined as progression following initial/prior therapy(ies).
Key exclusion criteria (32 listed)
- 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:
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| lerapolturevLerapolturev (5x10^7 TCID50) delivered intratumorally via convection enhanced delivery (CED). | Biological | lerapolturev + pembrolizumab |
| pembrolizumabPembrolizumab (200 mg IV) given every 3 weeks. | Biological | lerapolturev + pembrolizumab |
Primary outcome
Objective Response Rate (ORR)
Time frame: 24 months
Objective response rate (comprised of patients meeting an objective radiographic response or ORR): Patients achieving a complete response (CR) or partial response (PR).
Frequency and Severity of Treatment-emergent Adverse Events
Time frame: Up to 30 days after discontinuation of pembrolizumab
Count of participants experiencing a treatment-emergent adverse event is reported here. Detailed frequency and severity data are reported in the Adverse Event table.
Duration of Response (DOR)
Time frame: 24 months
DOR: Time from first ORR observed (once confirmed) until PD first observed (once confirmed) or death; whichever comes first.
Durable Radiographic Response (DRR)
Time frame: 24 months
DRR: An ORR that persists for ≥ 6 months.
2 secondary outcomes
Disease Control Rate (DCR)
Time frame: 24 months
Survival Assessed by Kaplan-Meier Methods
Time frame: 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lisa Franklin study director
Istari Oncology
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing lerapolturev and pembrolizumab in people with Glioblastoma and Recurrent Glioblastoma, run by Istari Oncology, Inc. at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: 24 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2025.