Peter R. Galle, MD of University Medical Center Mainz discusses his ESMO 2020 abstract – Updated results of a phase Ib study of regorafenib (REG) plus pembrolizumab (PEMBRO) for first-line treatment of advanced hepatocellular carcinoma (HCC).
Background
REG is an inhibitor of tyrosine kinase with immunomodulatory activity and PEMBRO is a monoclonal anti-PD-1 antibody. We have planned a phase Ib analysis of REG plus PEMBRO for first-line treatment of advanced HCC, based on possible synergistic effects.
Methodology
This is a dose-finding, continuing research of patients (pts) who have not had previous systemic therapy. In the first cohort, for 3 weeks on/1 week off plus PEMBRO 200 mg IV q 3 weeks, pts obtained REG 120 mg/day orally. The REG dose could be elevated (160 mg) or decreased (80 mg) in later cohorts; the PEMBRO dose is set. The key target is safety and tolerability. The secondary objective is to identify the maximum tolerated dose (MTD) and the prescribed dose of phase II and to determine the activity of the antitumor.
Outcomes
By April 29, 2020, a total of 36 pts of REG 120 mg had been treated. The median age was 66 years ( range 29-81); BCLC stage B / C was 31% /69% of pts; 100% Child-Pugh A; ECOG status 0/1 was 72% /28%. In 4/18 assessable pts, dose-limiting toxicities occurred: grade (Gr) 3 ALT / AST increased with Gr 2 bilirubin increased (n=2); Gr 3 rash (n=2). The MTD of the REG was 120 mg. Gr 3 or 4 treatment-31/36 pts (86 percent) of emergent adverse events (TEAEs) occurred; the most common are shown in the table below. The incidence of Gr 3 hand-foot skin reaction was 8%, 6% Gr 3 maculopapular rash, and 3% Gr 3 rash; no cases of Gr 4 rash were recorded. There have been one Gr 5 TEAE documented (not drug-related). TEAEs in 72 percent of pts contributed to a REG dose reduction or interruption and in 53 percent to a PEMBRO dose interruption. The median period of treatment (range) including pts ongoing for REG was 2.5 months (0.2-15.9) and PEMBRO was 3.5 months (0.03-19.2). 9 (28 percent) had a partial response and 20 (63 percent) had stable disease (RECIST 1.1) out of 32 evaluable pts; the rate of disease control was 91 percent.
Findings
For the first-line treatment of advanced HCC, the combination of REG plus PEMBRO showed no unexpected safety signals and promoted antitumor operation. The REG 80 mg plus PEMBRO assessment is ongoing. Table: 990P Table:
TEAEs (Gr 3/4 in pts of about 10 percent), n (percent) Gr 3 Gr 4
Increased AST 7(19)0 0
Increased ALT 5 (14) 2 (6)
Hypertension 5 (14) 0 Hypertension
Elevated bilirubin 5 (14) 0 0
Elevated lipase 4 (11) 1 (3)
MedDRA v22.0; grade CTCAE v4.03.ALT, aminotransferase alanine; AST, aminotransferase aspartate; TEAE, treatment-emergent adverse event.
Identification of Clinical Trial NCT’s03347292.