Background: In a phase Ib study, REG 120 mg/day plus PEMBRO for first-line treatment of advanced HCC showed no unexpected safety signals and encouraging anti-tumor activity. At the maximum tolerated dose (MTD) of REG (120 mg/day), approximately three-quarters of patients (pts) had a REG dose reduction or interruption due to a treatment-emergent adverse event (TEAE). Here, we present preliminary data for the REG 80 mg/day cohort. Methods: This is an ongoing, dose-finding study in pts who had no prior systemic therapy. In the first cohort, pts received REG 120 mg/day orally for 3 weeks on/1 week off plus PEMBRO 200 mg intravenously q 3 weeks. In later cohorts, the REG dose could be escalated (160 mg/day) or reduced (80 mg/day); the PEMBRO dose is fixed. The primary objective is safety and tolerability. Secondary objectives are to define the MTD and recommended phase II dose and assess anti-tumor activity. Results: By July 24, 2020, 16 pts were treated with REG 80 mg/day. Median age was 67 years (range 56–79), 25%/75% were Barcelona Clinic Liver Cancer stage B/C, 100% Child–Pugh A, and 69%/31% had Eastern Cooperative Oncology Group performance status 0/1. Grade (Gr) 3 TEAEs occurred in 8/16 pts (50%) and there were no Gr 4 TEAEs (Table); one pt experienced Gr 5 pneumonitis (not drug related). There were no reports of Gr 3 hand–foot skin reaction or Gr 3 maculopapular rash, and one report (6%) of Gr 3 rash. TEAEs led to a REG dose reduction or interruption in 50% of pts and to a PEMBRO dose interruption in 25% of pts. Median treatment duration (range) including pts ongoing was 4.1 months (0.4–7.1) for REG and 3.8 months (0.03–7.2) for PEMBRO. Of 13 evaluable pts, 2 (15%) had a partial response and 9 (69%) had stable disease (Response Evaluation Criteria in Solid Tumors v1.1); disease control rate was 85%. Conclusions: These preliminary results for the combination of REG 80 mg/day plus PEMBRO for first-line treatment of advanced HCC were consistent with the REG 120 mg/day cohort. The combination showed no unexpected safety signals and encouraging anti-tumor activity. Assessment of REG 80 mg/day plus PEMBRO is ongoing. Clinical trial information: NCT03347292

*Modification: Reductions or interruptions of REG; interruptions of PEMBRO.

Medical Dictionary for Regulatory Activities v23.0; Common Terminology Criteria for Adverse Events v4.03 grade.