In issue #4, Cassandra states that she has jumped back 12 years from this time period to late 1963 or early 1964, implying that this issue takes place in late 1975 or early 1976. This aligns very well with Ruth MacRae's apparent age in this issue.
Cassandra Locke's previous chronological appearance was in issue #9, her next chronological appearance is in issue #4. Her log entry in this issue is 125-4-27.
Doctor Strange's appearance here is explained in the letters pages of issues #12 and #5: He spent years in Asia, learning his craft at the side of the Ancient One, before returning to America to become a practicing mystic master. In fact, in his very first appearance (Strange Tales #110), it was revealed that the name of Doctor Strange was already "spoken in whispers". According to Roger Stern, it's quite possible that the Doctor Strange stories up through Strange Tales #122 actually took place before Fantastic Four #1.