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98 Background: P-PSMA-101 is an autologous CAR-T therapy targeting PSMA, with a high percentage of stem cell memory T cells (TSCM) associated with efficacy, safety, and bone homing (particularly relevant to prostate cancer). It is manufactured using a novel non-viral transposon system (piggyBac) that creates high TSCM products. Genes are inserted encoding a PSMA-targeted Centyrin CAR, iCasp9-based safety switch, and DHFR to purify CAR-T cells. P-PSMA-101 completely eliminated tumors in intractable murine models of prostate cancer, providing rationale for this phase 1 trial (NCT04249947). Methods: Patients with mCRPC treated with or not eligible for a CYP17 inhibitor or second-generation antiandrogen, and a taxane were enrolled. P-PSMA-101 was manufactured from apheresed T cells and administered IV following a standard 3-day cy/flu lymphodepletion regimen. Dose escalation from 0.25-15 x 106 cells/kg is planned. Results: As of September 30, 2021, P-PSMA-101 had been administered to 10 heavily pretreated patients (median 7 prior regimens; range 3-15). Single infusions of 0.25 (n=5) to 0.75 (n=5) x 106 cells/kg have been assessed, with dose escalation continuing. P-PSMA-101 cells were shown to expand in blood via qPCR assay, peaking 2-3 weeks after infusion, consistent with the high percentage of TSCM. Significant antitumor responses were seen in this preliminary data set. Declines in PSA were seen in 7 patients (>50% in 3 and >99% in 1). Of 4 patients who had pre- and post-treatment FDG and PSMA-PET imaging, 3 demonstrated marked to complete resolution of abnormal uptake at known metastatic disease sites, with concordance in bone and CT scans, and/or circulating tumor cells (CTC). In 1 case, post-treatment tumor biopsy demonstrated infiltration by P-PSMA-101 CAR-T cells and elimination of tumor cells (pathologic complete response). Safety was consistent with expectations for a CAR-T product. CRS was seen in 60% (10% Gr ≥3) of patients. DLT was seen in 1 patient with macrophage activation syndrome/uveitis, and was the only Gr ≥3 CRS event. Immune effector cell-associated neurotoxicity syndrome (ICANS) has not occurred. CRS marker elevations were modest (max IL-6: 642.6 pg/mL). The most common AEs were cytopenias, infections, and constitutional symptoms (Gr ≥3 60%, 10%, and 0%), as expected with lymphodepletion. Treatable related ocular AEs were noted in 3 patients. Conclusions: These results parallel preclinical findings that P-PSMA-101 can produce marked efficacy in mCRPC, and very low doses are highly efficacious, consistent with unique product attributes such as the TSCM phenotype and bone tropism. This is the first report demonstrating profound antitumor effects of a novel PSMA-directed CAR-T-cell platform with concordant biochemical, radiographic, and pathologic parameters, demonstrating that therapeutic benefit of unarmored CAR-T cells in a major solid tumor is possible. Clinical trial information: NCT04249947.

we compared the results and utility in clinical testing. Methods: Sixty eight retrospective Lung NSCLC FFPE samples were used for both DNA and RNA assays by clinically validated and/or FDA approved NGS panels Thermofisher Oncomine TM Focus assay / Oncomine comprehensive V3 Fusion (52 genes and 51 fusions drivers) and the AmoyDx R Pan Lung Cancer PCR Panel multiplex PCR assay (11 genes). Optimization of the PCR panel was done by the laboratory. Only gene targets present in both the NGS and PCR panel were used to show concordance. Other parameters for quality control including assay quality control and practical considerations were reviewed. Results: Preliminary analysis showed 93% (63/68) concordance for the DNA assay and 87% (59/68) concordance for the RNA assay. Up to 35% (21/68) of the samples showed suboptimal library quality control for the NGS assay but performed optimally on the PCR panel. There were differences in the requirements for input material, turn around time and costs. Conclusion: There was high concordance rate of the results between the assays. RNA quality in FFPE may show some limitations and performed better on the PCR panel. Both assays have their own advantages. Further evaluation and consideration in the clinical treatment roles will depend on practical evaluation in the laboratory and in the broader clinical testing environment.