Background: The current standard treatment for initially unresectable hepatocellular carcinoma (uHCC) is transarterial chemoembolization (TACE) or systemic treatments, but these approaches led to poor conversion resection rate. We aimed to investigate the clinical activity and safety of downstage conversion therapy with Sintilimab, a PD-1 inhibitor, Lenvatinib and TACE- HAIC (hepatic arterial infusion chemotherapy) in uHCC patients (PLATIC trial). Methods: This single-arm, Simon two-stage, phase 2 study was done at Sun Yat-sen University Cancer Center, Guangzhou, China. Patients received TACE-HAIC, followed by 200mg Sintilimab, Lenvatinib (8mg for BW < 60kg, 12mg for BW ≥ 60kg). The primary endpoint was the conversion to resection rate. Safety was analyzed in all patients who received at least one dose of treatment. This trial is closed to enrolment and is registered with ClinicalTrials.gov (NCT04814043). Results: Between May 19, 2021, and August 20, 2023, 57 patients were enrolled, and all were included in the efficacy and safety analysis set. The conversion to resection rate was 77.2% (44/57, 95% CI, 64.2 to 87.3) after a median 3 cycles of conversion therapy. Overall response rate was 77.2% per mRECIST and 42.1% per RECIST 1.1 criteria. The median duration of response (mDoR) was 11.5 months (95% CI, 9.8 to NA), and the median progression-free survival (mPFS) was 14.3 months (95% CI, 11.7 to 21.9). Treatment-related adverse events (TRAEs) of grade 3/4 were reported in 37 (64.9%) patients, with the most frequent being increased gamma-glutamyl transferase (36.8%), followed by abdominal pain (19.3%). Among 44 successful conversion patients, 29.5% (13/44) patients obtained a pathological complete response, with a mPFS of 15.3 months (95% CI, 11.9 to NA) and 12-month PFS rate of 59.4% (95% CI, 45.4 to 77.9). Conclusions: Sintilimab plus Lenvatinib and TACE-HAIC provided promising rate of conversion to resection in patients with initially unresectable HCC, with an acceptable TRAEs. Clinical trial information: NCT04814043.