T cells and pembrolizumab for recurrent and newly diagnosed glioblastoma

Two investigational products are being tested in this study as a combination immunotherapy strategy. The first product is allogeneic cytomegalovirus (CMV)-specific T cells. This product has previously been generated in a cell therapy manufacturing facility from the peripheral blood of healthy donors recruited via the Australian Bone Marrow Donor Registry or Australian Red Cross Lifeblood. Batches of product will be selected for participants based on human leukocyte antigen matching. The second product is pembrolizumab (Keytruda ®), supplied by MSD Australia. In phase I of the trial, the safety of escalating doses of the allogeneic CMV-specific T cells in combination with a fixed dose of pembrolizumab will be tested in 9–18 participants with recurrent glioblastoma multiforme/astrocytoma grade 4. Participants will be recruited from the Newro Foundation/Briz Brain & Spine. Each participant will receive four intravenous infusions of allogeneic CMV-specific T cells (at a dose of either 2 × 10^7 , 4 × 10^7 or 8 × 10^7 cells) suspended in normal saline. One infusion will be given per week. The Investigational Product will be administered intravenously over 5–10 min by a qualified person (e.g. nurse or clinician). This will be followed by a saline flush, which will take an additional 5–10 min. One week after the final infusion, participants will start receiving intravenous infusions of pembrolizumab (400 mg), which will continue every 6 weeks for up to 18 infusions. These infusions will be administered by a qualified person and will take 30 minutes, followed by a 5–10 min saline flush. The dose of allogeneic CMV-specific T cells for further exploration, in combination with pembrolizumab, will be determined in this phase, based on safety data. In phase II of the trial, the efficacy of allogeneic CMV-specific T cells in combination with pembrolizumab will be tested in 20 participants with recurrent glioblastoma multiforme/astrocytoma grade 4 and 20 participants with newly diagnosed glioblastoma multiforme/astrocytoma grade 4. These participants will be recruited from the Newro Foundation/Briz Brain & Spine, Royal Brisbane and Women’s Hospital, Princess Alexandra Hospital and The Austin Hospital. The infusion procedures from phase I, described above, will be followed for phase II, with the dose of T cells will be based on phase I data. Participants will attend clinic visits to receive the interventional treatment. All procedures will be recorded in the electronic database and monitored according to requirements. Participants from Phase I will not be eligible to participate in Phase II. It is anticipated that safety data from phase I will be reviewed within 3 months of the last participant completing their treatment on study, enrolment for Phase II will then begin after this review takes place. The dosing schedule for both Phase I and Phase II of Pembrolizumab (400mg), is every 6 weeks for up to 18 infusions.' - Participant duration is approximately 26 months.