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Reposted by Katherine Zhou

Nick DeVito @ndevitomd.bsky.social · Feb 5

Really cool study, not limited by the hematologic toxicity we have seen with other CD47 agents

Katherine Zhou @katherinezhoumd.bsky.social · Feb 5

20/31 #TumorBoardTuesday
🏫Mini Tutorial 17🏫
5) Phase 1/2, PT886 (CD47 x CLDN18.2 bispecific) in adv gastric/GEJ or PC (TWINPEAK, NCT05482893)
Promotes ADCC by NK cells, phagocytosis by macrophages
Part C, cohort 2: 1L adv PDAC w/ CLDN18.2 ≥2+ ≥10%, PT886 + chemo
Results pending

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Reposted by Katherine Zhou

Nick DeVito @ndevitomd.bsky.social · Feb 5

This was not an easy study to execute, in patients who have few other (if any) treatment options.

Here we can appreciate the monotherapy activity with a BiTE over a mAb.

Katherine Zhou @katherinezhoumd.bsky.social · Feb 5

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

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Reposted by Katherine Zhou

Nick DeVito @ndevitomd.bsky.social · Feb 5

Bispecifics are so in right now.

Learn more about them in this recent review: www.nature.com/articles/s41...

But now we need to understand a drug 🎯 and the immune system’s complex response modulation in its proximity

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Katherine Zhou @katherinezhoumd.bsky.social · Feb 5

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

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Katherine Zhou @katherinezhoumd.bsky.social · Feb 5

#PostTest Q2️⃣ #TumorBoardTuesday
👉🏽 Free CME 🔗 integrityce.com/TBT2024

🧐 Which of the following would you select for a 78-year-old man w/ mPDAC (CLDN18.2, 45%; MSS; gBRCA WT) and disease progression after gemcitabine/abraxane❓
1) FOLFIRINOX
2) Regorafenib trial
3) CLDN18.2 BiTe trial
4) Pembrolizumab

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Katherine Zhou @katherinezhoumd.bsky.social · Feb 5

#PostTest Q1️⃣ #TumorBoardTuesday
👉🏽#CME Eval 🔗 integrityce.com/TBTeval24
👉🏽ALL CME🔗 integrityce.com/TBT2024

🤔What percentage of pancreatic adenocarcinoma cases typically express Claudin 18.2?
1) 30%
2) 50%
3) 70%
4) 90%

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Katherine Zhou @katherinezhoumd.bsky.social · Feb 5

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

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Katherine Zhou @katherinezhoumd.bsky.social · Feb 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

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Katherine Zhou @katherinezhoumd.bsky.social · Feb 5

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

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Katherine Zhou @katherinezhoumd.bsky.social · Feb 5

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

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Katherine Zhou @katherinezhoumd.bsky.social · Feb 5

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)

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Katherine Zhou @katherinezhoumd.bsky.social · Feb 5

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

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Katherine Zhou @katherinezhoumd.bsky.social · Feb 5

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

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Katherine Zhou @katherinezhoumd.bsky.social · Feb 5

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

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Katherine Zhou @katherinezhoumd.bsky.social · Feb 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

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Katherine Zhou @katherinezhoumd.bsky.social · Feb 5

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

Waterfall plot for CT041 (CLDN18.2 CAR-T)

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Katherine Zhou @katherinezhoumd.bsky.social · Feb 5

21/31 #TumorBoardTuesday
🏫Mini Tutorial 18🏫
CLDN18.2 CAR-T Trials:
1) Phase 1, CT041 (CLDN18.2 CAR-T) in CLDN18.2+ adv GI cancers (NCT03874897)
AKA satricabtagene autoleucel (satri-cel)
98 pts got CT041: 75% gastric/GEJ, 10% panc, 8% intestinal, 4% BTC

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Katherine Zhou @katherinezhoumd.bsky.social · Feb 5

20/31 #TumorBoardTuesday
🏫Mini Tutorial 17🏫
5) Phase 1/2, PT886 (CD47 x CLDN18.2 bispecific) in adv gastric/GEJ or PC (TWINPEAK, NCT05482893)
Promotes ADCC by NK cells, phagocytosis by macrophages
Part C, cohort 2: 1L adv PDAC w/ CLDN18.2 ≥2+ ≥10%, PT886 + chemo
Results pending

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Katherine Zhou @katherinezhoumd.bsky.social · Feb 5

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

PM1032 (bispecific targeting CLDN18.2 and 41BB) in advanced solid tumors

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Katherine Zhou @katherinezhoumd.bsky.social · Feb 5

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

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Katherine Zhou @katherinezhoumd.bsky.social · Feb 5

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%

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Katherine Zhou @katherinezhoumd.bsky.social · Feb 5

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

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Katherine Zhou @katherinezhoumd.bsky.social · Feb 5

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

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Katherine Zhou @katherinezhoumd.bsky.social · Feb 5

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%

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Katherine Zhou @katherinezhoumd.bsky.social · Feb 5

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

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