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Primarily, it all comes down to Axiomantha's testimony at the very end of The Siege about Calcazar building a superweapon of unfathomable power, being connected to a tech-plague that she's not really convinced he actually understands (which if your character talked to the Farseer in Act 3 about, would probably be able to piece together the clear similarity between the tech-plague and the catastrophe that destroyed Crudarach), and that Theodora was a part of all this somehow. There's also the implication (if you found it in the environment) in Tervantias' lair and the direct claim in Heinrix's personal quest that Calacazar has been working with the Drukhari.
So I would say the character's motivation in pursuing Calcazar in Act 5 is... not necessarily to stop him, but to find out just what the hell he's up to, get answers as to his big plan and what it really is and how it has involved your family.
Not going to lie, it could definitely be explained and justified better. I think it really would have benefited from a scene between the RT and all the companions where the RT lays out the situation, the companions reply with their own motivations (for example, I think Yrliet would insist you go after Calcazar to learn about his connection to her Craftworld, Ulfar would insist you go after Calcazar to find out what he's been manipulating the Space Wolves for and getting his brothers killed for, Heinrix might based on your choices in his two personal quests up to this point either suggest that they need to find out what Calcazar is hiding because the potential consequences are incredible OR suggest that you leave Calcazar alone because the potential consequences of interfering are incredible, Abelard would probably suggest you leave Calcazar to his Inquisitorial business and focus on leading your Protectorate in this crisis but ultimately he'll support whatever decision you make, etc.), and ultimately the RT gives a decision and a reasoning. Maybe the RT is pursuing Calcazar to ensure the Expanse / Von Valancius Protectorate is protected from Calcazar's possible heresy / plans / unintended consequences, maybe the RT is pursuing Calcazar to get answers about their family and for their companions, maybe the RT wants to claim Calcazar's unfathomable weapon for the Von Valancius Dynasty... maybe even the RT decides that it is more important to stay with the Protectorate and not chase Calcazar into the unknown and we get an early ending similar to if you stubbornly refuse to become a Rogue Trader at the start of Act 1.
It's annoying because you're not the only person I've seen with some variation of this question. Though if you pay attention to what happens IN Act 5 it is very, very clear that pursuing Calcazar (regardless of your ultimate reason) is absolutely the RIGHT decision, so much of that seems to have been assumed retroactively by the writers and they really don't do enough to solidly justify (at least in a way that's clearly conveyed to the player) the RT taking the plunge in pursuing Calcazar.