Pirtobrutinib (formerly LOXO-305)

[MovingForward4423]

I gave patients this drug at 25 mg who had had five prior therapies and I was seeing response, and I have worked with other agents that were similar and not had that same experience, so there was something really unique about this molecule early on.

patientpower.info/navigatin...

[CycleWonder]

Interesting that the dose the author described was 25 mg compared to 200 mg in one of the ongoing trials

[MovingForward4423 in reply to CycleWonder]

Some of these new treatment's seem to be almost side effect free. In trials there were no instances of AF

[CycleWonder in reply to MovingForward4423]

I’m on the 200 mg dose and no AF

[Nicebaps]

I'm also from the UK and have been on Pirto since Oct 2022 under compassionate use. Pretty much zero side effects but sadly after 10 months use I have stopped responding positively. Next step (hopefully) will be Epcoritamab under trial 🤞

[SeymourB]

MovingForward4423 -

I too, am on 200mg, no AF. In the BRUIN trial paper below, the Phase 2 dose was 200mg.

I am in a trial of pirtobrutinib, obinutuzumab, and venetoclax for treatment naive at M.D. Anderson.

clinicaltrials.gov/study/NC...

I and another 5 of the first 7 were U-MRD6 (<1 CLL cell in 1,000,000 WBCs) at end of Cycle 4. There are about 40 of us in the trial, with more coming into it weekly.

The thing to also look besides side effects for relapsed/refractory CLL is the PFS. The BRUIN trial of pirto, rituximab, and venetoclax is still in progress. PFS was 19.6 months in a paper in patients enrolled between from March 21, 2019, through July 29, 2022. It's paywalled, but you can create a free account to read 2 articles a month.

nejm.org/doi/10.1056/NEJMoa...

Pirtobrutinib after a Covalent BTK Inhibitor in Chronic Lymphocytic Leukemia

July 6, 2023 N Engl J Med 2023; 389:33-44

That paper is the one that convinced the FDA to approve pirtobrutinib (Jaypirca) for CLL, even though it was a combo drug trial. The FDA Prescribing Information says that the response rate is what did it. But I think safety was a big factor, too.

accessdata.fda.gov/drugsatf...

Jaypirca Prescribing Information

I think the cost is comparable to other BTKi's, too. But the current trend seems to be toward fixed duration combos instead of treatment for life because of effectiveness with less financial toxicity. But neither the FDA approval nor the NCCN say whether it's continuous or not in r/r.

I see 10 trials of Pirtobrutinib that are Active or Recruiting:

clinicaltrials.gov/search?c...

There are 5 trials in the UK:

clinicaltrials.gov/search?c...

=seymour=