#tumorboardtuesday 🤔Hmmm....much more rapid disease progression on the CDK4/6🚫+AI - does this portend for a worse prognosis in subsequent lines of therapy❓

#tumorboardtuesday Any subtle differences in outcomes based on the specific mutation identified AKT vs. PTEN vs. PIK3CA❓

#TumorBoardTuesday 📢Join us Tuesday, 10-21-25 at 8PM ET as @drgattimays.bsky.social & @KennaKoehler 🗣️ Tx options after CDK4/6⛔️: What to consider in the 2nd line for HR+/HER2– mBC❓ RT and bring others into the discussion‼️

Tune in tomorrow 10/21/25 at 8pm EST for discussion about the ever changing landscape of 2L metastatic ER+ breast cancer #TBT #BCSM @tumorboardtuesday.bsky.social @osuwexmed.bsky.social #BreastCancer

Margaret Gatti-Mays, MD MPH@drgattimays.bsky.social · 10mo ago

🎙️Looking forward to a great #TBT discussion on Oct 21, 2025 on 2L ER+/HER2- #metastaticbreast cancer #BCSM @osuwexmed.bsky.social

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

25/31 #TumorBoardTuesday 🏫Mini Tutorial 22🏫 2) Phase 1b/2, CT041 in CLDN18.2+ adv gastric or panc (ELIMYN18.2, NCT04404595) 19 patients: 7 gastric/GEJ cancer, 12 pancreatic cancer doi.org/10.1200/JCO.2024.42.3_suppl.356

26/31 #TumorBoardTuesday 🏫Mini Tutorial 23🏫 58% panc pts had ≥3 prior lines PC: ORR 16.7%, mDOR 3.4 mos, CBR 33.3% At dose level 3, 2/5 PR in panc pts CRS mostly grade 1-2, 2 cases grade 3 ICANS grade 1 in 2 pts

27/31 #TumorBoardTuesday Back to our case🔎 Enrolled in CD3 x CLDN18.2 BiTE trial At 1 month, SD by CT but rising CA19-9 (206 -> 791)

28/31 #TumorBoardTuesday 🏫Mini Tutorial 24🏫 How about CLDN18.2 BiTE+X combos? 1) BiTE+chemo Chemo increases immunogenicity, depletes immunosuppressive Tregs (CD3-targeting BiTEs recruit polyclonal T cells, including Tregs) NCT05365581: ASP2138 (CD3 x CLDN18.2) ± chemo

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

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

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

23/31 #TumorBoardTuesday 🏫Mini Tutorial 20🏫 96.9% CRS, all grade 1-2 8% gastric mucosal injury, 1 pt w/ grade 3 No DLTs, treatment related deaths, ICANS

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

15/31 #TumorBoardTuesday 🏫Mini Tutorial 12🏫 CLDN18.2 bispecific trials: 1) Phase 1, Q-1802 (PD-L1 x CLDN18.2) (NCT04856150) 17 pts w/ adv gastric, PC, or BTC, mostly ≥3 prior lines 2/9 PRs, 4/9 SDs AEs: n/v, abd pain, GERD 24.1% G3 TRAEs doi.org/10.1200/JCO.2023.41.4_suppl.382

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

17/31 #TumorBoardTuesday 🏫Mini Tutorial 14🏫 3) Phase 1, IBI389 (CLDN18.2 x CD3) in adv PDAC (NCT05164458) 64 patients, median 2 prior lines 54.7% G3+ TRAEs: GGT increased, lymphs decreased, nausea 51.6% CRS, no grade 3+ TEAEs -> dose interruption 37.5%, discontinuation 4.7%

#TumorBoardTuesday Wow - that was worth the anticipation This is as a single agent (ADC)❓ This is as promising as all the (well deserved) hype with KRAS⛔

a man in a suit and tie is sitting at a desk and says " yes please "

ALT: a man in a suit and tie is sitting at a desk and says " yes please "

media.tenor.com

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

12/31 #TumorBoardTuesday Mini Tutorial 9 Trials of CLDN18.2 ADCs: 1) Phase 1, SYSA1802/EO3021 (CLDN18.2 ADC w/ MMAE) in adv solid tumors (NCT05980416) Promising results in gastric/GEJ, panc results pending TEAEs: nausea, anorexia, fatigue, diarrhea

#TumorBoardTuesday So - it seems like there is higher Claudin 18.2 expression in more advanced #PancreaticCancer - but interesting that its expression is not associated with survival🤔

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

10/31 #TumorBoardTuesday 🏫Mini Tutorial 7🏫 Trials of CLDN18.2 antibodies: 1) Phase 2, mPC w/ mod-strong CLDN18.2 IHC >75% randomized to 1L gem/abraxane ± zolbetuximab (NCT03816163) - results pending (rb.gy/yhczya)

9/31 #TumorBoardTuesday 🏫Mini Tutorial 6🏫 CLDN18.1 isoform is expressed in lung CLDN18.2 is dominant in gastric/pancreatic cancer (rb.gy/uwykch) % CLDN18.2+ seems to matter more than staining intensity (unlike HER2)

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

7/31 #TumorBoardTuesday 🏫Mini Tutorial 4🏫 More CLDN18.2+ if N+ (64% vs 40%) or M1 (79% vs 44%) CLDN18.2 not associated w/ survival (doi.org/10.4251/wjgo.v14.i7.1252) LN and liver mets also express CLDN18.2 (>60%) (doi.org/10.1002/ijc.28400)

6/31 #TumorBoardTuesday 🏫Mini Tutorial 3🏫 Transcription regulated by PKC signaling and CpG methylation Higher CLDN18.2 in gastric-type IPMN (vs intestinal-type), well-diff PDAC (vs poor-diff) doi.org/10.1002/jcb.23095