Background: Bruton tyrosine kinase (BTK) inhibition has shown clinical benefit in FL. Acalabrutinib is a highly selective, potent, covalent inhibitor of BTK. We evaluated acalabrutinib ± R in a Phase 1b study of patients (pts) with treatment-naive (TN) or relapsed/refractory (R/R) FL. Methods: Pts with R/R FL (≥1 prior treatment) were randomized to acalabrutinib (mono) or acalabrutinib + R (combo); TN pts received the combo. In 28-day cycles, R (375 mg/m² IV) was given weekly in Cycle 1 and on Day 1 of Cycles 2-6; acalabrutinib (100 mg PO bid [2 pts received 200 mg qd]) was given until progressive disease (PD) or intolerance. The primary endpoint was safety. Secondary endpoints included overall response rate (ORR), duration of response (DOR), pharmacokinetics (PK) and pharmacodynamics. Results: Thirteen TN and 27 R/R pts were treated. In all pts, the median age was 66 years (range 32-83), 98% of pts had ECOG PS ≤1, and 88% had stage III/IV disease. R/R pts received a median of 2 prior therapies (range 1-5). At a median follow-up of 22 and 7.6 months, 62% of TN and 26% of R/R pts, respectively, were still on treatment. Discontinuations were primarily due to PD (TN 15%; R/R 56%) and adverse events (AEs; TN 8%; R/R 11%). BTK occupancy and PK parameters were consistent with previous acalabrutinib studies. In all pts, common AEs (any grade) were fatigue (48%), headache (43%), diarrhea (40%), nausea (30%) and sinusitis (25%). Common Gr 3/4 AEs were hypertension (8%), increased alanine aminotransferase, increased aspartate aminotransferase, and cellulitis (all 5%), with no Gr 5 events. There were no cases of atrial fibrillation or Gr ≥3 hemorrhage. Efficacy outcomes are reported in the table. Conclusions: Acalabrutinib, alone and combined with R, was well-tolerated and yielded promising response rates in FL. These results support further evaluation of acalabrutinib in FL. Clinical trial information: NCT02180711

NR: not reached. ^a Pts dosed at 200 mg qd not included (1 SD, 1 PD). ^b Investigator assessed using Cheson 2014 criteria. ^c“+” indicates ongoing response.