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

  • STATUS
    Recruiting
  • End date
    Mar 30, 2023
  • participants needed
    30
  • sponsor
    Istari Oncology, Inc.
Updated on 30 June 2021
platelet count
karnofsky performance status
MRI
pembrolizumab
blood transfusion
aptt
glioblastoma multiforme
recurrent glioblastoma
supratentorial glioblastoma multiforme
methylated

Summary

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

Details
Condition Glioblastoma Multiforme, Malignant neoplasm of brain, Brain Tumor (Pediatric), Recurrent Glioblastoma, Supratentorial Glioblastoma, Brain Cancer, Brain Tumor, glioblastoma, supratentorial glioblastoma multiforme, brain tumors
Treatment Pembrolizumab, PVSRIPO
Clinical Study IdentifierNCT04479241
SponsorIstari Oncology, Inc.
Last Modified on30 June 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

18 years of age
Recurrent supratentorial glioblastoma confirmed via prior histology by the site's neuropathologist or designate
Histologically confirmed recurrent glioblastoma within 6 weeks of PVSRIPO infusion will not require a biopsy to confirm active tumor prior to catheter placement
Enhancing lesion 1 cm shortest diameter to 5.5 cm longest diameter in all planes
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
Within the enhancing portion or in the vicinity of enhancement of target lesion (ie, infiltrative disease)
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
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 PVSRIPO. 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/L (unsupported); 125,000/ L (can be supported via platelet transfusion) at biopsy/catheter placement
ANC 1000/L prior to biopsy/catheter placement
Creatinine 1.2 x ULN prior to biopsy/catheter placement
Total bilirubin, ALT, AST, ALP 2.5 x ULN prior to biopsy/catheter placement
PT and aPTT 1.2 x ULN prior to biopsy/catheter placement
If undetectable ATT 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

Exclusion Criteria

Excluded are
Received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or antiCTLA -4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) 12 weeks prior to PVSRIPO infusion (Note: does not apply for patients treated with pembrolizumab under this protocol who are eligible for PVSRIPO retreatment). Note: patients who had previously permanently discontinued any anti-PD-1 or PD-L1 therapy due to severe or life-threatening immune-related AE are excluded
Neoplastic lesions in the brainstem, cerebellum, or spinal cord
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
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
Extensive leptomeningeal disease: multiple lesions or lesions covering > 50% of leptomeninges. Tumor touching leptomeninges allowed
Requires treatment with high dose systemic corticosteroids, defined as dexamethasone > 4 mg/day or equivalent, within 2 weeks of PVSRIPO infusion
Has received systemic immunosuppressive treatments other than systemic corticosteroids (eg, methotrexate, chloroquine, azathioprine) within six months of PVSRIPO infusion
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
Prior interstitial brachytherapy, implanted chemotherapy, stereotactic radiosurgery or therapeutics delivered by local injection or CED, including PVSRIPO (except for qualifying patients being retreated with PVSRIPO within this trial)
Impending/life-threatening cerebral herniation syndrome, per neurosurgeon/designate
Severe, active co-morbidity, defined as follows
Infection requiring IV treatment/unexplained febrile illness (Tmax > 99.5F/37.5C)
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)
Known albumin allergy
Uncontrolled unexplained bleeding and/or hemoptysis within 4 weeks of planned PVSRIPO infusion
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%)
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%)
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