Calvin is interested in a lot of things, such as dinosaurs, philosophy, and making up stories. All of these things have something to do with one of the four core subjects (except math), which means that it would be very possible, if anyone took the effort, to adjust a lesson to be more interesting to Calvin. Part of the reason Calvin acts out so much is because he wants control over his learning environment, and relating lessons to his interests would likely make him feel like he has some control over his learning.
Calvin does make attempts to actually learn things, particularly about how the world works, but he doesn’t seem to get the opportunities to pursue these curiosities at school, and when he asks Dad questions, Dad gives him absolute (and often incorrect) answers instead of encouraging or helping Calvin look for an explanation. This prevents Calvin from digging deeper into this area of interest.
When lessons do apply to Calvin’s interests, he can get carried away in researching or engaging with his interests and miss the point of the actual lesson. The solution to that would be to encourage Calvin to a specific discovery outcome and provide reminders or guidance as necessary.
Another motivational pattern that Calvin has is that when he gets something wrong, rather than being allowed to make mistakes, he is often treated poorly for doing badly on tests or turning homework in late. By teaching mistakes and allowing them as part of learning and then shifting focus to the areas he is struggling with, it may actually motivate him to do better, especially if he is getting the attention he needs rather than being yelled at for being wrong.
Finally, in the majority of the comics, while Calvin is in the classroom, he doesn't get very much hands on learning. When building his own machines and being able to use his hands to learn, he learns quicker and is more motivated to try to make changes and fix his personal projects. By finding more classroom projects that allow him to dive in and use his hands, he may actually have more motivation to learn about the things they are doing in class by having an activity he enjoys, allowing his understanding of a topic to grow. Mrs.Wormwood tends to just hand out worksheets which causes Calvin's interest in the topic to take a nose dive for the worst.
With some extra adult guidance and attention, Calvin could be very motivated and eventually quite independent in his learning.