Nicholas Hornstein, Assistant Professor at Northwell Health, shared a post on X:
“One of the coolest abstract I’ve seen so far isn’t GI, and its a rapid oral most people have missed.
ARCHER: Prophylactic peptide targeting ALK resistance mutations in advanced ALK+ NSCLC
Abstract 8517
Presentation: Rapid Orals Lung, May 30
The usual cancer playbook is: Develop therapy – give therapy – resistance emerges – next therapy – repeat.
ARCHER presents alternative pathway:
What if we could short-circuit resistance before it happens? This is a new playbook altogether. In oncology, that usually runs into the brick wall of cumulative toxicity. But immune interception against predictable resistance mutations may be a way around that.
Also, can we please stop calling these ‘vaccines’? Yes, I know they technically are vaccines. But I also know how many patients hear that word and immediately shut down.
Quick hits:
- Phase 1b, first-in-human
- 15 patients with advanced ALK+ NSCLC
- All without progression on standard ALK TKI
Targeted 7 common ALK resistance mutations
Patients continued their ALK TKI
- Alectinib: 47%
- Lorlatinib: 33%
- Brigatinib: 20%
Immune response seen
- T cell responses in 10/14 evaluable patients
- Median 12-fold increase
- Responses included key resistance mutations
Safety was as excpted – Mostly grade 1 TRAEs
Disease control – 93% at median follow-up 11.5 months.
One fascinating detail: the single patient with oligoprogression after robust immune response developed KRAS G12D without a detectable ALK resistance mutation. This is not a normal mutation pattern in ALK+ disease.
That is exactly the kind of biologic signal that makes this so interesting. Similar efforts are ongoing in CRC and Panc (IE Elicio Therapeutics) Early with a tiny N. BUT, this is such a important idea and worth highlighting. Don’t wait for resistance. Anticipate it. Intercept it. Force the tumor down a different path. If I had millions of dollars in development money, I’d be throwing it at this idea.”
Other articles featuring Nicholas Hornstein on OncoDaily.