Background: InO, a CD22-directed antibody-drug conjugate, is approved to treat adults with R/R ALL. Historically, patients (pts) with Ph+ ALL (~20–30%) have had poor prognoses compared with Ph− pts. Methods: Pts with R/R ALL received InO in a phase 1 dose-finding/phase 2 study (1010; DeAngelo et al, Blood Adv 2017) and a phase 3 trial (1022; Kantarjian et al, NEJM 2016) comparing InO vs standard chemotherapy (SC). We analyzed outcomes in Ph+ pts (Ph chromosome or BCR-ABL gene by FISH) treated with InO (InO-1010 or InO-1022) or SC based on final data from each study. Results: In 1010 and 1022, respectively, 16 and 22 Ph+ pts received InO; 27 Ph+ pts were randomized to SC in 1022 (22 received SC). Pts in 1010 were heavily pretreated. Among Ph+ pts in 1022, 19 (86%) InO pts and 26 (96%) SC pts had previous tyrosine kinase inhibitors (TKIs). Prior stem cell transplants (SCT) were 8 (50%) for InO-1010, 7 (32%) for InO-1022, and 9 (33%) for SC. Also, 15 (94%), 10 (45%), and 15 (56%) pts were treated in ≥2nd salvage for InO-1010, InO-1022, and SC, respectively. Efficacy outcomes are shown (Table). A total of 3 (19%) InO-1010 pts, 9 (41%) InO-1022 pts, and 5 (19%) SC pts proceeded to SCT after treatment. The most common nonhematologic grade 3-4 adverse events with InO in Ph+ pts were gastrointestinal disorders (31%) in 1010 and multi-organ laboratory abnormalities (41%) in 1022; 2 Ph+ pts in each InO study had veno-occlusive liver disease. Among SC pts, infections (55%) were the most common grade 3-4 nonhematologic events. Clinical trial information: NCT01363297Conclusions: In Ph+ pts with R/R ALL who failed prior TKIs +/- SCT, InO-treated pts had higher rates of CR/CRi, MRD negativity, and subsequent SCT. However, overall outcomes in 1022 InO vs SC were still inferior to those reported in Ph– pts; thus additional treatment combinations should be explored.