7/18 #TumorBoardTuesday 👩🏻‍🏫Mini Tweetorial 4🏫 💊Several FDA👍PIK3CA-inhibitors: Capivasertib or Alpelisib or Inalvosalib 🤔 When and how do you PIK one of the PIK3CA of the 3 available? ☝️Inavolisib+Fulvestrant+Palbo is approved for 1st line mER+ BC after recurrence on/after adjuvant ET therapy

7/18 #TumorBoardTuesday 👩🏻‍🏫Mini Tweetorial 4🏫 💊Several FDA👍PIK3CA-inhibitors: Capivasertib or Alpelisib or Inalvosalib 🤔 When and how do you PIK one of the PIK3CA of the 3 available? ✌️Alpelisib & Capivasertib are approved in 2nd line mER+ BC combined with fulvestrant 🔎 NGS results, Baseline A1C

7/18 #TumorBoardTuesday 👩🏻‍🏫Mini Tweetorial 4🏫 💊Several FDA approved PIK3CA-inhibitors: Capivasertib or Alpelisib or Inalvosalib 🤔 When and how do you PIK one of the PIK3CA of the 3 available? 📎 pubmed.ncbi.nlm.nih.gov/33246021/

8/18 #TumorBoardTuesday Back to our case🔎 👩‍🦳 Patient received Capivasertib + Fulvestrant due to PIK3CA mutation. 👉 Not yet considered endocrine resistant so would not move onto capecitabine, sacituzumab 👉 Tumor is HER2 negative so no role for trastuzumab deruxtecan

8/18 #TumorBoardTuesday Back to our case🔎 👉 Everolimus + fulvestrant is not favored given the more targeted approach with Capivasterib for the PIK3CA mutation ✅ Tolerated therapy well with mild rash at start of treatment that resolved with antihistamines

9/18 #TumorBoardTuesday ⏭️ Case 2 #TumorBoardTuesday #OncTwitter Case 2 👩‍🦳 62 y.o. postmenopausal female 💉 mBC to the🫁, ER 70%, PR 85%, HER2⛔[IHC 1] 🩻 confirmed⬆️Dz on 1L ribo/letrozole at C7 🏃‍♀️ ECOG PS 1. No co-morbidities. ⛔ Normal vital signs, labs 🩸Liquid Biopsy shows ESR1 mutation, TMB-High

10/18 #TumorBoardTuesday 👩🏻‍🏫Mini Tweetorial 5🏫 🤔When is a patient considered to be “endocrine resistant”? Per Advanced Breast Cancer International Consensus Guidelines, Link to Guidelines: www.thebreastonline.com/article/S096...

10/18 #TumorBoardTuesday 👩🏻‍🏫Mini Tweetorial 5🏫 👉 Recurred on adjuvant endocrine tx 👉 Recurred <2y after adjuvant endocrine tx 👉 ⬆️Dz<6mos of starting 1L mBC tx 👉 ⬆️Dz after any duration of >=2nd line of ET-based therapy 👉 Known ESR1 mutation [now have 2 Rx for ESR1m → elacestrant or imlunestrant]

11/18 #TumorBoardTuesday 👩🏻‍🏫Mini Tweetorial 6🏫 EMERALD 👩‍🦳 2L metastatic HR+/HER2- received 💊 Elacestrant, an oral selective ER Degrader (SERD) ✅ 1-2 prior ET including CDK4/6i and < 1 chemo 💊 Elacestrant 400mg daily vs 💉fulvestrant or 💊AI ⬆️⬆️ PFS for prior💊 CDK4/6i > 12 mon with ESR1 mutated tumors

11/18 #TumorBoardTuesday 👩🏻‍🏫Mini Tweetorial 6🏫 ⬆️ Elacestrant benefited all subgroups including: 🦴only, 🫁 visceral mets, > 3 mets ⬆️ Elacestrant benefited all🧬subgroups: ✔️ESR1+PIK3CA, ✔️ESR1+TP53, ✔️ESR1+HER2-low 🤢 Most common AE: N/V

3/18 #TumorBoardTuesday 👩🏻‍🏫Mini Tweetorial 2🏫 CAPItello-291 👩‍🦳 mER+/HER2- breast cancer with PD on AI +/- CDK4/6i 💉2L Fulvestrant +/- capivasertib [oral, 🚫AKT plus.. 🚫PTEN, 🚫PIK3CA] ...continued

3/18 #TumorBoardTuesday 👩🏻‍🏫Mini Tweetorial 2🏫 CAPItello-291 ✅ Capivasertib + fulvestrant ⬆️mPFS in AKT Pathway alterations [7.3m vs 3.1m] ✅ Capi+Fulvestrant benefited all subgroups including: 🦴only, 🫁 visceral mets, prior💊 CDK4/6i, prior ☣️chemo 📎https://www.nejm.org/doi/full/10.1056/NEJMoa2214131

4/18 #TumorBoardTuesday 👩🏻‍🏫Mini Tweetorial 3🏫 CAPItello-291: Capivasertib Side effects 💊 Capivasertib taken 4 days on, 3 days off per week 🩺 Need baseline A1C < 8% 🚽 Most common AE: Diarrhea onset ~ day 8 [All grades 72%, G3/4 9.3%] ...continued

4/18 #TumorBoardTuesday 👩🏻‍🏫Mini Tweetorial 3🏫 CAPItello-291: Capivasertib Side effects ☝️ Rash (12%) onset ~ day 12→ Pretreat with oral antihistamine, topical steroids 💉 Hyperglycemia (18%) onset ~ day 15; ⬇️ G3/G4 than other PIK3CA 📎https://www.esmoopen.com/article/S2059-7029(24)01466-2/fulltext

5/18 #TumorBoardTuesday Back to our case🔎 💉 57yo ♀️ with mBC to the 🦴, liver, ER 100%, PR 95%, HER2⛔[IHC 0]-🩻confirmed⬆️Dz on 1L ribo/letrozole at C47 ✅ Normal labs (A1C=5.8) & VS 🩸Liquid Biopsy: +PIK3CA mutation, TP53 mutation, TMB-Low (4 mut/mb), High tumor fraction (> 5%) 👩🏻‍⚕️What 2L Tx is advised❓

6/18 #TumorBoardTuesday POLL What 2L therapy would you give this patient❓ 1) Capecitabine 2) Trastuzumab deruxtecan 3) Sacituzumab govetican 4) Capivasertib + Fulvestrant 5) Everolimus + Fulvestrant

2/18 #TumorBoardTuesday 👩🏻‍🏫Mini Tweetorial 1🏫 ...cont 📝Tissue-based assays or plasma-based assays (ctDNA) can be used ☝️Some alterations may be better detected by tissue-based assays like homozygous loss of PTEN or TMB-H. ☝️Liquid assays may reflect tumor heterogeneity more accurately

2/18 #TumorBoardTuesday 👩🏻‍🏫Mini Tweetorial 1🏫 Actionable Mutations in 2L mER+/HER2- BC 🧬Several actionable mutations in 2L+ mBC: ESR1, PIK3CA, AKT, PTEN, BRCA (germline, somatic) 🔍Evaluation of acquired mutations at progression will help to direct therapy options Cont.....

#TumorBoardTuesday POLL What would you do next❓ 1) Start capecitabine 2) Liquid biopsy to assess for actionable mutations 3) Start trastuzumab deruxtecan 4) Check tumor markers Ca 15-3 & Ca 27.29

1/18 #TumorBoardTuesday @KennaKoehler & @drgattimays.bsky.social Case 1 👩‍🦳57 y.o. postmenopausal female 📋Well controlled DM (A1C = 5.8) 🏃‍♀️ECOG PS 0 💉Metastatic BC to bones, liver, ER 100%, PR 95%, HER2- [IHC 0] w/scan confirmed progression on 1L ribociclib/letrozole at C47 in bones ⛔ Normal labs & VS

#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‼️

#TumorBoardTuesday 🧠And while we finalize the case details, collect FREE #CME 👉🏽https://integrityce.com/tbt2025

#TumorBoardTuesday ➡️Before @drgattimays.bsky.social & @KennaKoehler 🗣️ 2nd line Tx options for HR+/HER2– mBC, #BCSM tell us your connection to this medical🩺discussion 👇👇🏼👇🏾 1) Onc/Surg/Rad/IR/Gyn Onc 2) Other MD/APP/RN/Pharm D 3) Patient/Patient Advocate 4) Fellow/Resident/Trainee

✅This #TumorBoardTuesday🗣️with @KennaKoehler & @drgattimays.bsky.social‬ is provided by @IntegrityCE 👍Supported by ed grants from Exelixis, Ferring, Ipsen, Lilly, Janssen Scientific Affairs, Merck & Taiho Oncology 🙏 👉🏽Info about 🆓 CME: integrityce.com/tbt2025

#PreTest Q1️⃣#TumorBoardTuesday Free #CME integrityce.com/tbt2025 B4 @KennaKoehler & @drgattimays.bsky.social‬🗣️2nd-line Txs for #breastcancer, test your🧠with these 2❓

🤔What 2L Tx would you offer a 45yo♀️w/ AKT mutated, ER+/HER2- mBC after⬆️Dz on ribociclib➕AI/OFS❓ 1) Capecitabine monotherapy 2) Capivasertib+fulvestrant 3) Elacestrant monotherapy 4) Everolimus + fulvestrant

#PreTest Q2⃣#TumorBoardTuesday 🧐 A 75yo♀️w/ER+/HER2- PIK3CA+ mBC is starting 2L therapy with alpelisib+fulvestrant. Baseline A1C=6.1 & BMI is 33. What steps can limit risk for severe hyperglycemia❓ 1) Labs QW x 2, then monthly 2) Baseline A1C, then q3 mos 3) Consider metformin 4) All of the above

#ASCO25 📢Join me & my colleagues EileenMOReilly, Gabi Chiorean, & Brian Wolpin to discuss #PancreaticCancer management in a case-based format 📅Friday, May 30th, 6:30- 8:00pm CDT 📍Sheraton Grand Chicago Riverwalk 4th Floor 📋Link to Registration: (tinyurl.com/mra3pt9s

@hopkinspress.bsky.social #GIOnc 📢Launching Day 2⃣‼️ 😀I am confident that today's sessions will be as GREAT as yesterday's sessions So - join us NOW for this 3rd Annual Johns Hopkins Updates in Gastrointestinal Cancers Conference

@hopkinspress.bsky.social #GIOnc 📢We are underway‼️ 😀Join us today and tomorrow for our 3rd Annual Johns Hopkins Updates in Gastrointestinal Cancers Conference ✅As always - the conference is free to register and all sessions are available streaming🖥️on line integrityce.com/Hopkins25Str...

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

#TumorBoardTuesday BOOKMARK THIS DISCUSSION‼️ Thank you so much @ndevitomd.bsky.social & @katherinezhoumd.bsky.social 🙏 That was an amazing summary of what we know to date about targeting Claudin 18.2 in #PancreaticCancer

#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%

#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

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

This is a good question, and we cannot reliably infer this from available transcriptional datasets as RNA doesn’t correlate to protein expression Time for a microarray? Patients with these rare cancers need therapeutic options.

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

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

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

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

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

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

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