Table 3.

Ongoing Clinical Trials with Regorafenib-Based Combination Treatments (www.clinicaltrials.gov)

Clinical Trials Identifier	Official Title	Phase	Therapy Line	Intervention/Treatment	Status
NCT04183088	Regorafenib Plus Tislelizumab as First-line Systemic Therapy for Patients With Advanced Hepatocellular Carcinoma	II	First	Tislelizumab+regorafenib for part 1. Tislelizumab+regorafenib for group 1 of part 2. Placebo+regorafenib for group 2 of part 2.	Not yet recruiting
NCT04170556	The GOING Study: Regorafenib Followed by Nivolumab in Patients With Hepatocellular Carcinoma Progressing Under Sorafenib	I/IIa	Second^	Regorafenib 160 mg/day 3 weeks on and 1 week off. Nivolumab at the dose of 1.5 mg/kg, 3 mg/kg or 240 mg/infusion every 2 weeks. Dose will be adjusted depending on the incidence of adverse events.	Recruiting
NCT04310709	Phase II Study of Regorafenib-nivolumab Combination Therapy for Chemotherapy-naïve Patients With Unresectable or Metastatic Hepatocellular (RENOBATE)	II	First	Nivolumab 480 mg IV on Day 1, every 4 weeks. Regorafenib 80 mg per oral once daily for 21 consecutive days starting on Day 1, every 4 weeks.	Recruiting
NCT04777851	Phase III, Multicenter, Randomized, Open-Label Trial to Evaluate Efficacy and Safety of Regorafenib in Combination With Nivolumab Versus TACE for First-Line Treatment of Intermediate-Stage HCC With Beyond Up-to-7 Criteria	III	First	Investigational arm: regorafenib at a dose of 90 mg orally once per day (on days 1 to 21 of a 28-day cycle), in combination with nivolumab 480 mg using 30-minutes intravenous infusion (on day 1 of a 28-day cycle, every 4 weeks). Control arm: Patients will be treated with transarterial chemoembolization (TACE) “on-demand” according to the clinical site’s standards, with the goal of controlling all known liver lesions. Either conventional TACE (cTACE) or drug-eluting bead transarterial chemoembolization (DEB-TACE) may be used (as long as it is consistently applied for all patients at a given clinical site).	Not yet recruiting
NCT04718909	Regorafenib Combined With Sintilimab Versus Regorafenib Alone as the Second-line Treatment for Unresectable Hepatocellular Carcinoma	II	Second	Experimental Arm: Regorafenib: 160 mg p.o. qd for 3 weeks of every 4 week cycle (ie, 3 weeks on, 1 week off). Sintilimab: 200mg i.v. q3w. Active Comparator: Regorafenib: 160 mg p.o. qd for 3 weeks of every 4 week cycle (ie, 3 weeks on, 1 week off).	Recruiting
NCT03475953	A Phase I/II Study of Regorafenib Plus Avelumab in Solid Tumors	I/II	≥ 1 previous line (s) of systemic therapy	3 dose levels of Regorafenib given in combination with Avelumab followed by 7 phase II trials to evaluate the association of Regorafenib at the RP2D§ with Avelumab in 7 distinct settings (advanced or metastatic tumors).	Recruiting
NCT04696055	An Open-Label Study of Regorafenib in Combination With Pembrolizumab in Patients With Advanced or Metastatic Hepatocellular Carcinoma (HCC) After PD1/PD-L1 Immune Checkpoint Inhibitors	II	Prior 1L immunotherapy with a PD-1/PD-L1 checkpoint inhibitor administered either as monotherapy or in combination with other therapies	Pembrolizumab 400 mg to be administered as an intravenous (IV) infusion every 6 weeks (Q6W). Regorafenib will be given orally (p.o.) at a starting dose of 90 mg QD for 3 weeks of every 4 weeks (ie, 3 weeks on, 1 week off). If the starting dose of 90 mg daily is well tolerated the dose should be escalated to 120 mg starting after the first 4-week cycle of regorafenib.	Recruiting
NCT03347292	A Multicenter, Non-randomized, Open-label Dose Escalation Phase Ib Study of Regorafenib in Combination With Pembrolizumab in Patients With Advanced Hepatocellular Carcinoma (HCC) With no Prior Systemic Therapy	I	First	Dose escalation: The regorafenib starting dose will be 120 mg q.d. (once daily) 3 weeks on/1 week off in combination with the recommended dose of pembrolizumab (200 mg Q3W). Pembrolizumab dose will not be escalated or de-escalated. Dose expansion: Dose expansion cohorts will continue to be expanded until the sample size of 30–35 patients per cohort is reached.	Active, not recruiting

Note: ^Patients progressing under first-line sorafenib.

Abbreviation: ^§RP2D, recommended phase II dose.