Neoadjuvant Immunotherapy for Hepatocellular Carcinoma

Figures & data

Table 1 Neoadjuvant Immunotherapy Trials Underway in HCC

Trial Name/NCT Identifier	Design	Key Inclusion Criteria	Intervention(s)	Key Primary Endpoint(s)	N
PRIMER-1/NCT05185739	Multicenter randomized 3-arm trial	HCC by histology or radiology and low surgical risk	6 weeks of neoadjuvant therapy, randomization 1:1:1 to one of 3 groups: ● Pembrolizumab, ● Lenvatinib ● Pembrolizumab/Lenvatinib	Major pathologic response rate, proportion of patients with less than 10% viable tumor at resection	60
DYNAMIC/NCT04954339	Single-arm, single institution	Potentially resectable BCLC stage B/C or high-risk resectable HCC	● 2 cycles neoadjuvant atezolizumab/bevacizumab prior to resection ● 4 cycles of adjuvant atezolizumab/bevacizumab	Rate of pathologic complete response (pCR) defined by the absence of viable tumor cells in any nodule	45
NCT04658147	2 arm, randomized, single institution	Resectable HCC	Randomization to 10 months of one of 2 groups: ● Nivolumab ● Nivolumab/Relatlimab	Number of patients who complete neoadjuvant treatment and proceed to surgery within 4 years	20
NCT03510871	Multicenter, single-arm, open-label trial	HCC, potentially eligible for curative surgery	● Neoadjuvant ipilimumab/nivolumab for 2 or 4 cycles ● Eligible patients will undergo surgery	Percentage of subjects with tumor shrinkage (> 10% of decrease of the sum of the target lesions according to RECIST 1.1)	40
NCT04123379	Single center, multiple arms	HCC or NSCLC, surgical candidate for resection of tumor	HCC subgroup with 3 possible cohorts: ● Neoadjuvant nivolumab 2 cycles prior to surgery/adjuvant nivolumab 3 times following surgery ● Same regimen with CCR2/5-inhibitor twice daily for 28 days prior to surgery ● Nivolumab with anti-IL-8 dosed once prior to surgery	- Major pathologic response (MPR) within 2 years, MPR is defined as <10% viable tumor within resection - Significant tumor necrosis (STN) - necrosis of >70% of tumor base on pathologic analysis of gross tumor resection	50
NCT03867370	Open-Label, Multi-Center	Resectable HCC with histological or cytological confirmation	Randomization to one of 3 cohorts: ● Single dose of neoadjvuant toripalimab prior to resection, after resection adjuvant toripalimab wil be given every 3 weeks for up to 48 weeks. ● Single dose of neoadjvuant toripalimab given with levnatinib prior to resection, after resection adjuvant toripalimab with lenvatinib for up to 48 weeks ● Single dose of neoadjvuant toripalimab given with lenvatinib prior to resection, after resection adjuvant toripalimab alone for up to 48 weeks	Pathologicresponse rate	40
NCT04850040	Prospective, single-arm, single-center clinical trial	Locally advanced, potentially resectable HCC, including tumor thrombus	Neoadjuvant camrelizumab in combination with apatinib mesylate and oxaliplatin	Major pathologic response (MPR) defined as ≤10% of tumor at time of surgery	15
MEDI4736/NCT05194293	Prospective, multicenter, single arm trial.	HCC, clinical stage T1b/T2 or T3	Regorafenib in combination with durvalumab given until surgery or for up to 2 years post registration unless discontinuation criteria met.	Objective response rate (ORR) at 16 weeks	27
NCT04888546	Single center, single arm trial	Resectable HCC, Child Pugh A or B	Neoadjvuant anlotinib hydrochloride oral tablets in combination with TQB2450 (novel anti-PD-L1 monoclonal antibody) prior to hepatic resection.	Pathologic complete response rate (pCR) and overall response rate (ORR)	20
NCT04224480	Single center, single arm study	Resectable HCC, Child-Pugh <6	Neoadjuvant pembrolizumab 4 weeks prior to resection, adjvuant pembrolizumab starting 4 week after surgical resection for up to 12 months.	HCC recurrence within 2 years after hepatic resection, correlates including phenotype of immune cells in the tumor microenvironment after tumor resection	20
CAPT/NCT04930315	Prospective, single arm, randomized trial	Resectable HCC, BCLC B or C if technically resectable, Child-Pugh A	Randomization to one of 2 arms: ● Neoadjuvant and adjuvant group - 4 cycles of neoadjuvant camrelizumab in combination with apatinib for 3 cycles, with adjuvant camrelizumab for up to 8 cycles ● Adjuvant group - camrelizumab given for up to 12 cycles after resection	1-year tumor recurrence-free rate	78