library(data.table)
A = data.table(Col1 = 1:4, Col2 = 4:1, Col3 = letters[1:4])
# Col1 Col2 Col3
#1: 1 4 a
#2: 2 3 b
#3: 3 2 c
#4: 4 1 d
B = data.table(Col1 = c(1,3,5), Col2 = c(4,2,1))
# Col1 Col2
#1: 1 4
#2: 3 2
#3: 5 1
A[!B, on = c("Col1", "Col2")]
# Col1 Col2 Col3
#1: 2 3 b
#2: 4 1 d