Abstract Disclosure: M. Fleseriu: Consulting Fee; Self; Amryt (fka Chiasma), Ipsen, Ionis Pharmaceuticals Inc., Recordati, Pfizer, Inc. Research Investigator; Self; Amryt(fka Chiasma), Crinetics, Ionis Pharmaceuticals Inc., Recordati. Other; Self; Deputy Editor at EJE. A. Dreval: Research Investigator; Self; Research Investigator: Amryt(fka Chiasma). Y. Pokramovich: Research Investigator; Self; Research Investigator: Amryt(fka Chiasma). I. Bondar: Research Investigator; Self; Amryt(fka Chiasma). E. Isaeva: Research Investigator; Self; Chiasma. D.P. Macut: Research Investigator; Self; Principle Investigator: Amryt(fka Chiasma). Speaker; Self; Novartis Pharmaceuticals, Novo Nordisk, Sanofi, Pfizer, Inc., (spouse) Novo Nordisk. Other; Self; member of the Executive Committee of the European Society of Endocrinology (ESE). M.E. Molitch: Consulting Fee; Self; Corcept, Janssen Research & Development Company, Merck, Novo Nordisk, Pfizer, Inc., Novartis Pharmaceuticals. Grant Recipient; Self; Amryt(fka Chiasma), Crinetics, Ionis Pharmaceuticals Inc. Research Investigator; Self; Bayer, Inc. N.V. Leonova: Research Investigator; Self; Chiasma. G. Raverot: Consulting Fee; Self; Pfizer, Inc., Recordati Rare Diseases, Ipsen. Research Investigator; Self; Chiasma, Pfizer, Inc., Novartis Pharmaceuticals. Speaker; Self; Ipsen, Pfizer, Inc., Recordati Rare Diseases. A. Haviv: Employee; Self; Amryt(fka Chiasma). N. Biermasz: Advisory Board Member; Self; Recordati, Pfizer, Inc., Macro Registry. Grant Recipient; Self; Amryt(fka Chiasma). C.J. Strasburger: Advisory Board Member; Self; Sandoz, Ipsen, Recordati. Consulting Fee; Self; Ascendis, Amryt(fka Chiasma), Novo Nordisk, Merck, Sandoz, Recordati. Speaker; Self; Ipsen, Novo Nordisk, HRA Pharmaceuticals. S. Melmed: Advisory Board Member; Self; Ionis Pharmaceuticals Inc., Crinetics. Consulting Fee; Self; Ipsen. Grant Recipient; Self; Pfizer, Inc. Background: Oral octreotide capsules (OOC) are a treatment option for patients with acromegaly in several countries. Global MPOWERED trial (NCT02685709; Fleseriu et al, Lancet Diabetes Endocrinol. 2022; 10: 102-111)1 showed that OOC were noninferior to injectable somatostatin receptor ligands (iSRLs; octreotide or lanreotide) in maintenance of biochemical response in those previously responding to both OOC and iSRLs. Clinical characteristics predictive of response are useful to devise and implement personalized acromegaly treatment. Objective To identify patient and disease characteristics to predict the likelihood of OOC responsiveness. Methods Eligibility criteria included adults aged 18-75 years, acromegaly diagnosis at screening, and ≥6 months iSRL treatment (≥4 months responding to stable dose). All patients received OOC during the 26-week run-in phase. Responders at week 24 (IGF-I <1.3 × ULN and mean integrated GH <2.5 ng/mL) were randomized to receive OOC or iSRLs during the subsequent randomized controlled treatment (RCT) phase.1 Multivariate logistic regression analyses were performed to assess the relationship of baseline characteristics with OOC response during the run-in phase by comparing the group randomized to the RCT phase (those responding at end of run-in who opted to continue, n=92) to the group not randomized (n=54). Results One hundred forty-six patients enrolled in the run-in phase; 116 patients completed, 94 OOC responders, 92 randomized to RCT phase. IGF-I level prior to initiating OOC was the only predictor of response in the run-in phase for randomization into the RCT phase; randomized mean (SD) 0.8 × ULN (0.25), not randomized 1.0 × ULN (0.25), adjusted P<.0001. Other acromegaly characteristics, including duration of acromegaly, history of surgery and/or radiation, baseline pituitary adenoma size, residual postoperative pituitary adenoma size, GH level (randomized mean [SD] 0.78 ng/mL [0.644]; not randomized 1.06 ng/mL [1.010]), and signs/symptoms of GH excess (eg, joint pain, fatigue, sweating, swelling of extremities, snoring, sleep apnea, carpal tunnel syndrome, headache, and others) were not associated with subsequent OOC response (adjusted P=.11-P=1.0). Prior iSRL dose received was not a predictor of OOC response (adjusted P=1.0); randomized n (%): low dose 19 (20.7), middle 33 (35.9), high 40 (43.5); not randomized: low 11 (20.4), middle 22 (40.7), high 21 (38.9). Conclusions Baseline IGF-I level on iSRLs, but not other acromegaly baseline characteristics, were the sole predictor of subsequent OOC response. This IGF-I-value association may be expected, as response at end of run-in was determined by a strictly defined IGF-I cutoff. These results may guide clinicians considering transitioning patients with acromegaly from iSRLs to OOC. Presentation: Thursday, June 15, 2023