This Phase 1 single arm trial in patients with rGBM will characterize the safety, tolerability and initial efficacy of PVSRIPO intratumoral infusion followed by intravenous pembrolizumab 14 to 28 days later, and every 3 weeks, thereafter.
Objective response rate (comprised of patients meeting an objective radiographic response, ORR): Patients achieving a CR or PR. Duration of esponse (DOR): Time from first ORR observed (once confirmed) until rogressive Disease (PD) first observed (once confirmed) or death; whichever comes first. Durable radiographic response (DRR): An ORR that persists for ≥ 6 months.
Baptist MD Anderson Cancer Center
1.Greater or equal 18 years of age.
2.Histologically confirmed, recurrent, supratentorial glioblastoma; progression of primary glioblastoma or transformation from a lower grade to a higher grade acceptable.
3.Enhancing lesion greater than or equal to 1 cm shortest diameter to less than or equal to 5.5 cm longest diameter in all planes.
4.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:
a.Within the enhancing portion or in the vicinity of enhancement of target lesion (ie, infiltrative disease).
b.greater than or equal to 0.5 cm from ventricles.
c.greater than or equal to 1 cm deep into the brain.
d.greater than or equal to 0.5 cm from corpus callosum.
5.First or second relapse supported by MRI or CT scan; relapse is defined as progression following initial/prior therapy(ies).
6.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.
7.Karnofsky Performance Status greater than or equal to 70 at screening and baseline.
8.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.
9.Ability to safely discontinue anti-coagulant therapy(ies) prior to biopsy/catheter placement, as required per site/surgical guidelines.
10.Hemoglobin greater than or equal to 9 g/dL prior to biopsy/catheter placement.
11.Platelet count greater than or equal to 100,000mL (unsupported); greater than or equal to 125,000/mL (can be supported via platelet transfusion) at biopsy/catheter placement.
12.ANC greater than or equal to 1000 prior to biopsy/catheter placement.
13.Creatinine less than or equal to 1.2 x ULN prior to biopsy/catheter placement.
14.Total bilirubin, ALT, AST, ALP less than or equal to 2.5 x ULN prior to biopsy/catheter placement.
15.PT and aPTT less than or equal to 1.2 x ULN prior to biopsy/catheter placement.
16.If undetectable ATT IgG at screen, Tdap booster vaccine greater than or equal to 1 week prior to biopsy/catheter placement.
17.Patients must be willing and able to understand and provide written informed consent.
1.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 PVSRIPO infusion. Note: Patients who permanently discontinued any of the above therapies for severe or life-threatening immune-related reactions are excluded.
a.Neoplastic lesions in the brainstem, cerebellum, or spinal cord.
b.Radiological evidence of active/growing multifocal disease: no size increase > 0.5 cm in any direction on 2 consecutive MRI at least 3 months apart of any other enhancing nontarget lesions present at baseline.
c.Tumors with greater than or equal to 1cm of contrast-enhancing tumor component crossing the midline (crossing the corpus callosum).
d.Extensive subependymal disease: multiple lesions or lesions covering > 50% of subependymal space. Tumor touching subependymal space allowed.
e.Extensive leptomeningeal disease: multiple lesions or lesions covering > 50% of leptomeninges. Tumor touching leptomeninges allowed.