Not sure about ampullary, but this ASCO 2024 poster found CLDN18.2 IHC 2+/3+ in 35% of small bowel adenocarcinomas (including 49% duodenal)
doi.org/10.1200/JCO.2024.42.16_suppl.4176

31/31 #TumorBoardTuesday
🏫Mini Tutorial 27🏫
Choice of CLDN18.2 BiTE vs CAR-T?
BiTE: off the shelf, continuous therapy
CAR-T: autologous (takes time), one infusion
doi.org/10.1186/s13045-021-01067-5

30/31 #TumorBoardTuesday
🏫Mini Tutorial 26🏫
3) BiTE+OV
Oncolytic virus -> tumor lysis -> T cell response
SQ model of KPC w/ human CLDN18.2 in CD3ε humanized mice:
OV-BiTE improved tumor control and survival compared to OV-GFP or PBS ctrl
doi.org/10.1016/j.omto.2023.08.011

29/31 #TumorBoardTuesday
🏫Mini Tutorial 25🏫
2) BiTE+ICI
BiTEs -> inhibitory checkpoints upregulated
KPC orthotopic model:
CLDN18.2 x CD3 BiTE + αPD1 -> decreased tumor growth compared to BiTE or αPD1 alone
doi.org/10.1053/j.gastro.2023.06.037

24/31 #TumorBoardTuesday
🏫Mini Tutorial 21🏫
Pooled analysis of CT041 in met panc (NCT03874897, NCT04581473)
24 pts with advanced panc
ORR 16.7%, DCR 70.8%
mPFS 3.3 mos, mOS 10 mos
mDOR 9.5 mos, DOR 50% at 12 mos
AEs: CRS, GI
doi.org/10.1200/JCO.23.02314

22/31 #TumorBoardTuesday
🏫Mini Tutorial 19🏫
ORR 38.8%, DCR 91.8%, mDOR 6.4 mos
Among 10 pts with PDAC: 2 PR, 7 SD, 1 PD
doi.org/10.1038/s41591-024-03037-z

19/31 #TumorBoardTuesday
Mini Tutorial 16
4) Phase 1/2, PM1032 (CLDN18.2 x 41BB bispecific) in adv solid tumors (NCT05839106)
Activates T and NK cells
30 patients, no DLTs, 66.7% CLDN18.2+
14 gastric/GEJ, 10 panc, 5 other GI
17 CLDN18.2+ pts at ≥5 mg/kg: 2 PR, 7 SD

18/31 #TumorBoardTuesday
🏫Mini Tutorial 15🏫
Efficacy for 600 µg/kg in CLDN18.2 IHC 2+/3+ ≥10%:
27 pts, 8 PRs, 11 SDs, ORR 39.6%, DCR 70.4%
DOR and PFS not reached

16/31 #TumorBoardTuesday
🏫Mini Tutorial 13🏫
2) Phase 1, ASP2138 (CD3 x CLDN18.2 BiTE) ± chemo in CLDN18.2+ adv gastric/GEJ or PC (NCT05365581)
2+1: 2 CLDN18.2 binding sites, 1 CD3 binding site

14/31 #TumorBoardTuesday
🏫Mini Tutorial 11🏫
CLDN18.2 IHC 1+/2+/3+ ≥40%: ORR 28% (all PRs: 5 PDAC, 2 BTC), DCR 80%
CLDN18.2 ≥60%: ORR 38.5% (all PRs: 4 PDAC, 1 BTC), DCR 84.6%
25.7% G3+ TRAEs: anemia, neutropenia, elevated AST
Dose interruption 20%, discontinuation 2.9%

13/31 #TumorBoardTuesday
🏫Mini Tutorial 10🏫
2) Phase 1, IBI343 (CLDN18.2 ADC w/ exatecan) in PDAC or BTC (NCT05458219)
35 patients enrolled: 28 PDAC, 7 BTC (all pretreated)
Dose expansion: CLDN18.2 IHC 1+/2+/3+ ≥40%
doi.org/10.1200/JCO.2024.42.16_suppl.3037

11/31 #TumorBoardTuesday
🏫Mini Tutorial 8🏫
2) Phase 1b, 1L FG-M108 + gem/abraxane for advPC w/ CLDN18.2 IHC 1+/2+/3+ ≥10% (NCT04894825)
FG-M108: afucosylated human CLDN18.2 mAb w/ enhanced ADCC
ORR 50%, DCR 100% among 14 pts
SEs: nausea, emesis, neutropenia, anemia

8/31 #TumorBoardTuesday
🏫Mini Tutorial 5🏫
Ventana CLDN18 43-14A RxDx assay
FDA approved for zolbetuximab in gastric/GEJ adeno
43-14A binds intracellular domain, does not distinguish CLDN18.2 vs CLDN18.1
doi.org/10.1038/s41571-024-00874-2

5/31 #TumorBoardTuesday
🏫Mini Tutorial 2🏫
CLDN18.2 ectopically expressed in PanIN (97%), IPMNs (95), MCNs (80%), PDAC (70%), but not normal pancreatic duct (doi.org/10.1369/0022155411420569)

🏫Mini Tutorial 1🏫
CLDN18.2
In normal gastric mucosa: part of tight junctions, not accessible
In gastric cancer: becomes exposed -> targetable
doi.org/10.1038/s41571-024-00874-2

1/31 #TumorBoardTuesday
73yo M w/ PDAC met to abd wall, R pelvis, and b/l inguinal canals
S/p Whipple + 6 mos adj FOLFIRINOX 3 yrs ago for T2N1 disease
1L gem/abraxane -> PD after 4 mos w/ slight growth of abd wall met (2.8 -> 3.2 cm)
ECOG PS 1