Background: BR101801, a triple inhibitor of PI3Kγ/δ and DNA PK, inhibits not only the signal affecting cell growth caused by PI3Kγ/δ but also efficiently induces cell cycle arrest and apoptosis through inhibition of DNA-PK activation, and finally decreases the stability of oncogenic protein, c-Myc(AACR2020 abstract #655). We initiated a first-in-human study to investigate BR101801 across advanced hematologic malignancies that had relapsed or was refractory to the standard therapies. Methods: This is a phase 1, open-label, multi-center, dose escalation (1a), and expansion (1b) study of BR101801 in adult patients with advanced hematologic malignancies including relapsed/refractory(R/R) B-cell lymphoma, CLL/SLL, and PTCL (NCT04018248). Dose was escalated at 50, 100, 200 and 325 mg QD. PTCL-NOS, AITL, FTCL and Nodal PTCL with TFH phenotype were included for dose expansion study at 200mg as RP2D. Results: 12 patients with advanced hematologic malignancies were enrolled in phase 1a study and treated with 50-325mg of BR101801. The median age was 63 years (range 30-76 years). Histological subtypes include AITL (n = 5, 41.7%), PTCL-NOS (n = 3, 25.0%), DLBCL (n = 2, 16.7%), MZL (n = 1, 8.3%) and MF (n = 1, 8.3%). Of 7 evaluable patients with PTCL (PTCL-NOS and AITL), ORR was 42.9% (95% CI, 9.9-81.6) and CBR was 85.7% (95% CI, 42.1-99.6). In median follow-up duration of 22.5 months, mPFS was 22.2 months (95% CI, 3.6-22.2) and mOS has not yet reached. Duration of response of the 3 responders were 9.2, 14.1+ and 20.7+ months, respectively. Safety was analyzed in 12 patients. 10 patients (83.3%) experienced ≥1 ADRs. The most common (≥ 10%) ADRs were Rash (33.3%), ALT increased (33.3%), AST increased (25.0%), and Diarrhea (16.7%). Grade 3 ADRs occurred in 6 patients (50.0%) and those were ALT increased (25.0%), AST increased (16.7%), Rash (16.7%), erythema multiforme (8.3%), and neutropenia (8.3%). All ADRs were manageable and has recovered. There were no Grade 4 or 5 ADRs and no treatment related death observed. DLTs were occurred at 325mg; thus, 200mg QD was determined as the MTD and RP2D. The pharmacokinetics data showed an ideal profile in general. The PK results did not remarkably deviate from the non-clinical studies, and a more thorough interpretation will be performed in phase Ib. In phase 1b study, 7 PTCL patients were enrolled and it is ongoing till enrollment of total 12 patients. Conclusions: The results for the phase 1a study evaluated the safety, efficacy results and pharmacokinetic characteristics, 200 mg QD was shown to provide target exposure for clinical efficacy with the tolerable and safe profile. BR101801 showed of antitumor activity, especially in R/R PTCL patients. Hence, the phase 1b study of BR101801 is warranted in R/R PTCL patients and we expect BR101801 would become a promising therapeutic option for these patients. Clinical trial information: NCT04018248.