What third line treatment do you consider for a patient with metastatic pancreatic cancer with good functional status and no targetable mutations after progression on FOLFIRINOX and gemcitabine/nab-paclitaxel?

Sadly, there is absolutely no "standard" option in this space, as no trials have demonstrated any meaningful benefit.

I personally would not just "try" a therapy - and I would especially not just "try" an immune checkpoint inhibitor, as these, as single agents have shown no benefit at all (if the tumor is MSS).

Sometimes, there are any mitigating details from the prior therapy. Just as one example, if the patient had prolonged control on FOLFIRINOX (e.g. 12 months or more), but had to stop the oxaliplatin due to neurotoxicity after only 4-6 months, then that could be a reason to try FOLFOX.

One other consideration is the breadth of the molecular profiling panel used for testing. A small percentage of pancreatic cancer patients have tumors...

Agree with a thorough look for an actionable alteration and/or a phase I trial if possible.

There may be a very modest benefit of nal-Iri in PC after FOLFIRINOX according to a recent retrospective study, so previous irinotecan may not always mean there is no benefit from Nal-Iri based therapy. Would certainly try that rather than erlotinib+gem.

Napoli-1 trial.

Consider Liposomal Irinotecan with 5FU, Leucovorin.