CTIM-35 - INB-400 Phase 1b/2 Drug Resistant Immunotherapy With Activated, Gene Modified Allogeneic or Autologous γδ T Cells  in Combination With Maintenance Temozolomide Recurrent or Newly Diagnosed Glioblastoma

Gamma delta (gd) T cells are innate immune cells that synergistically target cancer cells via NKG2D ligands (NKG2D-L) upregulated by chemotherapy. INB-200, a Phase 1 trial, demonstrated the safety and efficacy of autologously (auto) derived genetically modified drug resistant immunotherapy (DRI) gd T cells combined with maintenance temozolomide (TMZ) to treat newly diagnosed (ND) patients with GBM. Initiation of , a 3-arm phase 1b/2 study confirming the efficacy of the auto product in ND GBM and the safety and efficacy of an allogeneic (allo) product in both ND and relapsed GBM has begun. Arm A assesses the auto product in ND GBM patients with 1x10⁷ cells delivered on Day 1 of cycles 1-6 along with TMZ maintenance therapy per the Stupp regimen. In the Phase 1b arm, the haploidentical allo product, will be assessed for safety in 6 relapsed GBM patients who will receive 1x10⁷ cells in combination with 150mg/m² of TMZ on Day 1 of every six 28-day cycles. Arm B will continue enrollment of relapsed patients following the Phase 1b and Arm C will test the safety of the allo derived product in ND, GBM patients. In Arm C, patients will receive 1x10⁷ allo DeltEx DRI cells on Day 1 of cycles 1-6 in combination with TMZ maintenance. Cells are administered through a Rickham catheter in all arms. Primary endpoints for the Phase 1b define the RP2D and subject/ product characteristics to optimize manufacturing, while Phase 2 endpoints will determine the 12 mos OS rate for Arms A & C and 9 mos OS rate for Arm B. Eligible patients are adults with IDH-wt ND or relapsed GBM with no concurrent TTF or immunotherapy, willing to place an indwelling Rickham catheter. Allo arm patients must have a haploidentical donor. Fifteen US centers will conduct study.