Background: Our experience of B7H3 chimeric antigen receptor T cells (CAR-T) revealed modest engraftment (max 4.9 cells/uL) and no objective responses on first infusion. Previous CD19 CAR T cell trials have revealed that host B Cell CD19 can drive robust engraftment and persistence even in the absence of malignant CD19 expression. We therefore developed a bispecific B7H3xCD19 CAR T cell with the intent of using host CD19 expression to drive better engraftment of the B7H3-targeting CAR. Methods: Young patients with relapsed/refractory solid tumors (R/RST) were enrolled onto a Phase 1 trial (NCT04483778) to examine the safety of autologous T cells lentivirally transduced to express either or both scFV-IgG4hinge-CD28tm-4-1BB-zeta B7H3-specific and CD19-specific CARs. The B7H3 CAR construct contained the methotrexate resistance/selection cassette DHFRdm and the tracking/suicide construct EGFRt and the CD19 CAR construct containing the tracking/suicide construct HER2tg, allowing for differential CAR tracking. CAR T cells were cultured in low-dose methotrexate to select for B7H3 containing CAR T cells and limit exposure to monospecific CD19 CAR T cells. All patients received lymphodepleting fludarabine and cyclophosphamide prior to infusion of cryopreserved CAR-T at the prescribed dose level. The maximal tolerated dose or biologically effective dose (BED) was determined based upon observed toxicity through day 28 from initial CAR-T infusion and using a 3+3 statistical design. Results: 11 subjects (age 5-23, median 18 years) enrolled and received dose level (DL) 0B (0.5 x 10⁶ TOTAL CAR-T/kg, n = 7) or DL1B (1 x 10⁶ TOTAL CAR-T cells/kg, n = 4). One subject experienced dose limiting toxicities at DL1 of transaminitis, hyponatremia, worsening of a pericardial effusion and hypoxia. Most common toxicities were cytokine release syndrome (CRS) (n = 4, maximum CTCAE grade 2).No occurrence of ICANS was noted. Maximum total circulating CAR-T expansion on first infusion was 796.3 cells/uL and max B7H3 expansion was 374.2 cells/uL with 7/11 continuing with ongoing detection of CAR T cells in the peripheral blood at time of last follow up (21 days to 8 months). CAR engraftment was predominated by the B7H3 CAR single expressing CAR T cells in all subjects. All subjects developed B cell aplasia which is ongoing in 10/11 subjects at time of last check (range of 21 days to 8 months). Best overall response of Stable Disease was observed in 2 of the 11 subjects infused. Conclusions: B7H3xCD19 CAR T cells robustly engraft and expand in patients with R/RST and are safe, but despite ongoing detection of the CAR T cells, no objective responses were observed. It is likely that additional measures will be required to enhance the activity of CAR-T cells to achieve objective responses. STRIvE-02 Arm C will explore the addition of pembrolizumab post bispecific CAR infusion to evaluate the effect of PD1 blockade on anti-tumor activity. Clinical trial information: NCT04483778.