The Comparison of Kte-X19 to Current Standards of Care: A Pre-Specified Synthetic Control Study Utilizing Individual Patient Level Data from Historic Clinical Trials (SCHOLAR-3)

Background: The ZUMA-3 trial of KTE-X19 in relapsed/refractory (r/r) adult B-cell precursor acute lymphoblastic leukaemia (B-ALL) utilizes a single arm design. To contextualize these results, a synthetic control (SC) study derived from individual patient-level data (IPD) sampled from historical clinical trials (CTs) was constructed. Aims: To compare the overall survival (OS) and objective complete response rate at week 24 (OCR24) results of the ZUMA-3 pivitol study using a matched (SC) derived from IPD from CTs. Methods: This study had two distinct phases: firstly, CTs from which patients were sampled were identified using the medidata enterprise data store (MEDS). The second phase of this study constructed SCs to the ZUMA-3 population, one SC for patients naïve to blinatumomab (blin) or inotuzuamab (ino) therapy (SCA-1) and one in blin or ino pre-treated patients (SCA-2). All analysis were pre-specified and conducted by an external third party to Kite Pharma. For the trial identification phase, the MEDS database was searched to identify CTs that had inclusion and exlusion criteria congruent with ZUMA-3 and treatment assignments representative of current standards of care inclusive of blin, ino or chemotherapy regimens. Once appropriate CTs had been identified the endpoints were re-engineerd to match the same defintions as the ZUMA-3 trial. For the SC construction phase, propensity score (PS) matching was used. The PS was derived as a function of the number of previous lines of therapy, prior allo-SCT, age, sex, ECOG, Philadelphia chromosome status, percentage bone marrow blasts and extramedullary disease. For outcomes analysis, time-to-event endpoints of interest were analyzed using the Kaplan-Meier method and compared using a Cox proportional hazard regression model. OCR rate was described through crude incidence rates and corresponding 95% CI. ln addition, an odds ratio together with associated 95% CI and 2-sided p-value were estimated from a logistic regression model. Results A total of 20 SCA-1 patients were matched to 20 patients from ZUMA-3 and a total 20 SCA-2 patients were matched to 29 patients from ZUMA-3. Analysis of the SCA-1 cohort shows an OCR24 of 85% (95% CI 62.1%, 96.8%) in the Zuma-3 patients and 35.0% (95% CI 15.4, 59.2) among propensity matched controls. This corresponds to an OR of 10.5 (95% CI 2.3, 48.7; p-value 0.0031). No OCR24 data was available for SCA-2. A post hoc analysis was conducted in order to further contextualize the OCR