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@TumorBoardTues 1/23 #TumorBoardTuesday #GastricCancer #OncTwitter @MPishvaian @JohnEbbenMDPhD @KlempnerSam
56 year old 👨🏼
PMH: obesity and GERD
😣 Develops abdominal discomfort
🍛 early satiety
⬇️ 20lb weight loss
🩻 CT: Gastric thickening and bilobar liver lesions
🤨 What would you do?

@TumorBoardTues @MPishvaian @JohnEbbenMDPhD @KlempnerSam 2/23 #TumorBoardTuesday #GastricCancer @CentralParkWMD @odub75
🧪CEA increased to 200 ng/mL
🔦EGD: ulcerated mass in body of stomach
🔬Path: poorly differentiated adenocarcinoma
🧪Initial IHC: pMMR and HER2 negative and PD-L1 CPS 1
🤔 What additional tests would you do next?

@TumorBoardTues @MPishvaian @JohnEbbenMDPhD @KlempnerSam @CentralParkWMD @odub75 @jeremyldavismd @jdekervel @drharrietbk @andresc27622123 @svalpione @ken_k_ @filipherpe @selmaahcenedjab @arifi34261933 @drjunaidarsh @jordanberlin5 @AnaRuizW @JafferAjaniMD @ronanhsieh @RonaYaeger @SteveMaronMD @RyanMoyMDPhD @bernabecarolina @HardingJJMD @choong_kun @Betzabe100

@TumorBoardTues @MPishvaian @JohnEbbenMDPhD @KlempnerSam @CentralParkWMD @odub75 @JeremyLDavisMD @JDekervel @DrHarrietBK @AndresC27622123 @SValpione @KEN_K_ @FilipHerpe @SelmaAhcenedjab @Arifi34261933 @drjunaidarsh @jordanberlin5 @AnaRuizW @JafferAjaniMD @ronanhsieh @RonaYaeger @SteveMaronMD @RyanMoyMDPhD @BernabeCarolina @HardingJJMD @choong_kun @Betzabe100 3/23 #TumorBoardTuesday @MHLars @TaberneroJosep @NataliyaUboha
#GI21 #GastricCancer
While waiting for results...
👨🏼Discuss clinical trial options and screen for anti-CLDN18.2 based studies
IHC following central review: positive >75% staining
📚@KlempnerSam #ASCOGI21

@TumorBoardTues @MPishvaian @JohnEbbenMDPhD @KlempnerSam @CentralParkWMD @odub75 @JeremyLDavisMD @JDekervel @DrHarrietBK @AndresC27622123 @SValpione @KEN_K_ @FilipHerpe @SelmaAhcenedjab @Arifi34261933 @drjunaidarsh @jordanberlin5 @AnaRuizW @JafferAjaniMD @ronanhsieh @RonaYaeger @SteveMaronMD @RyanMoyMDPhD @BernabeCarolina @HardingJJMD @choong_kun @Betzabe100 @MHLars @TaberneroJosep @NataliyaUboha @KevinCSoaresMD @SunnieSKim @GABOUALFA @mdbrunocosta @TimothyJBrownMD @NajeebAl_Hallak @DrElkhoueiry @CrozrX @SKamath_MD @rprobinpark @realbowtiedoc @chase_wasson @SepideBesharati @StomachlessPA @SumeraIlyasMD @zapatalaguadomd @youngkwangchae @smitha42 @carycottongi @ChrisManzMD

@TumorBoardTues @MPishvaian @JohnEbbenMDPhD @KlempnerSam @CentralParkWMD @odub75 @JeremyLDavisMD @JDekervel @DrHarrietBK @AndresC27622123 @SValpione @KEN_K_ @FilipHerpe @SelmaAhcenedjab @Arifi34261933 @drjunaidarsh @jordanberlin5 @AnaRuizW @JafferAjaniMD @ronanhsieh @RonaYaeger @SteveMaronMD @RyanMoyMDPhD @BernabeCarolina @HardingJJMD @choong_kun @Betzabe100 @MHLars @TaberneroJosep @NataliyaUboha @KevinCSoaresMD @SunnieSKim @GABOUALFA @mdbrunocosta @TimothyJBrownMD @NajeebAl_Hallak @DrElkhoueiry @CrozrX @SKamath_MD @rprobinpark @realbowtiedoc @chase_wasson @SepideBesharati @StomachlessPA @SumeraIlyasMD @zapatalaguadomd @youngkwangchae @smitha42 4/23 #TumorBoardTuesday
👨🏼‍🏫Mini tweetorial 1 👨🏻‍🏫
📌SOC systemic tx for metastatic #GastricCancer
‼️Always consider clinical trials‼️
🧬Biomarkers drive therapy
✨NEW✨ 8/2023 @NCCN to include 1L IO for dMMR/MSI-H (Finally🙌🏽)
📚#MariaAlsina @TaberneroJosep nature.com

nature.com/articles/s4157…

@TumorBoardTues @MPishvaian @JohnEbbenMDPhD @KlempnerSam @CentralParkWMD @odub75 @JeremyLDavisMD @JDekervel @DrHarrietBK @AndresC27622123 @SValpione @KEN_K_ @FilipHerpe @SelmaAhcenedjab @Arifi34261933 @drjunaidarsh @jordanberlin5 @AnaRuizW @JafferAjaniMD @ronanhsieh @RonaYaeger @SteveMaronMD @RyanMoyMDPhD @BernabeCarolina @HardingJJMD @choong_kun @Betzabe100 @MHLars @TaberneroJosep @NataliyaUboha @KevinCSoaresMD @SunnieSKim @GABOUALFA @mdbrunocosta @TimothyJBrownMD @NajeebAl_Hallak @DrElkhoueiry @CrozrX @SKamath_MD @rprobinpark @realbowtiedoc @chase_wasson @SepideBesharati @StomachlessPA @SumeraIlyasMD @zapatalaguadomd @youngkwangchae @smitha42 @NCCN 5/23 #TumorBoardTuesday
👨🏼‍🏫Mini tweetorial 2👨🏻‍🏫
📌CLAUDIN 18.2
📍Transmembrane tight junction in gastric epithelia
❌Not routinely in norm tissue outside gastric mucosa (cancer-restricted antigen)
📍expressed in tumor types
🔸Gastric
🔹GEJ
🔸Biliary
🔹Pancreas

@TumorBoardTues @MPishvaian @JohnEbbenMDPhD @KlempnerSam @CentralParkWMD @odub75 @JeremyLDavisMD @JDekervel @DrHarrietBK @AndresC27622123 @SValpione @KEN_K_ @FilipHerpe @SelmaAhcenedjab @Arifi34261933 @drjunaidarsh @jordanberlin5 @AnaRuizW @JafferAjaniMD @ronanhsieh @RonaYaeger @SteveMaronMD @RyanMoyMDPhD @BernabeCarolina @HardingJJMD @choong_kun @Betzabe100 @MHLars @TaberneroJosep @NataliyaUboha @KevinCSoaresMD @SunnieSKim @GABOUALFA @mdbrunocosta @TimothyJBrownMD @NajeebAl_Hallak @DrElkhoueiry @CrozrX @SKamath_MD @rprobinpark @realbowtiedoc @chase_wasson @SepideBesharati @StomachlessPA @SumeraIlyasMD @zapatalaguadomd @youngkwangchae @smitha42 @NCCN 6/23 #TumorBoardTuesday
👨🏼‍🏫Mini tweetorial 3
✨Claudin18.2 (CLDN18.2)
🎯Tumor intrinsic surface targets - multi therapeutic approaches
🎯Avail strategies
Engineered mAb
Bispecific Ab
Antibody-Drug
CAR-T
🪚If you can hit it, you can kill it
📚Cao Biomark Res
biomarkerres.biomedcentral.com

biomarkerres.biomedcentral.com/articles/10.11…

Claudin18.2 is a novel molecular biomarker for tumor-targeted immunotherapy - Biomarker Research

The claudin18.2 (CLDN18.2) protein, an isoform of claudin18, a member of the tight junction protein...

@TumorBoardTues @MPishvaian @JohnEbbenMDPhD @KlempnerSam @CentralParkWMD @odub75 @JeremyLDavisMD @JDekervel @DrHarrietBK @AndresC27622123 @SValpione @KEN_K_ @FilipHerpe @SelmaAhcenedjab @Arifi34261933 @drjunaidarsh @jordanberlin5 @AnaRuizW @JafferAjaniMD @ronanhsieh @RonaYaeger @SteveMaronMD @RyanMoyMDPhD @BernabeCarolina @HardingJJMD @choong_kun @Betzabe100 @MHLars @TaberneroJosep @NataliyaUboha @KevinCSoaresMD @SunnieSKim @GABOUALFA @mdbrunocosta @TimothyJBrownMD @NajeebAl_Hallak @DrElkhoueiry @CrozrX @SKamath_MD @rprobinpark @realbowtiedoc @chase_wasson @SepideBesharati @StomachlessPA @SumeraIlyasMD @zapatalaguadomd @youngkwangchae @smitha42 @NCCN 7/23 #TumorBoardTuesday
👨🏼‍🏫Mini tweetorial 4👨🏻‍🏫
📌Zolbetuximab
👨🏼enrolled ph3 Zolbe+ox chemo
⚛️MOA
🎯1st-in-class chimeric IgG1 mAb target CLDN18.2 inducing antibody & complement dependent cytotox
🔹studied
mono
combo + 1L chemo
combo + anti-PD-1
📚@KoheiShitara #ASCOGI23 #GI23

@TumorBoardTues @MPishvaian @JohnEbbenMDPhD @KlempnerSam @CentralParkWMD @odub75 @JeremyLDavisMD @JDekervel @DrHarrietBK @AndresC27622123 @SValpione @KEN_K_ @FilipHerpe @SelmaAhcenedjab @Arifi34261933 @drjunaidarsh @jordanberlin5 @AnaRuizW @JafferAjaniMD @ronanhsieh @RonaYaeger @SteveMaronMD @RyanMoyMDPhD @BernabeCarolina @HardingJJMD @choong_kun @Betzabe100 @MHLars @TaberneroJosep @NataliyaUboha @KevinCSoaresMD @SunnieSKim @GABOUALFA @mdbrunocosta @TimothyJBrownMD @NajeebAl_Hallak @DrElkhoueiry @CrozrX @SKamath_MD @rprobinpark @realbowtiedoc @chase_wasson @SepideBesharati @StomachlessPA @SumeraIlyasMD @zapatalaguadomd @youngkwangchae @smitha42 @NCCN @KoheiShitara 8/23 #TumorBoardTuesday
👨🏼‍🏫Mini tweetorial 5
✨FAST
📍Ph2
🔹Zolbe +/- EOX
👍🏽PFS: intermed/High express (>40%) mPFS 7.5 v 5.3 mos HR (95% CI) 0.44 (0.29-0.67); P<.0005
Greater benefit➡️IHC express cut off >70% 9 v 5.7 mos HR 0.38 (0.23-0.62) P<0.005
📚#Sahin annalsofoncology.org

annalsofoncology.org/article/S0923-…

FAST: a randomised phase II study of zolbetuximab (IMAB362) plus EOX versus EOX alone for first-line treatment of advanced CLDN18.2-positive gastric and gastro-oesophageal adenocarcinoma

Claudin 18.2 (CLDN18.2) is contained within normal gastric mucosa epithelial tight junctions; upon m...

@TumorBoardTues @MPishvaian @JohnEbbenMDPhD @KlempnerSam @CentralParkWMD @odub75 @JeremyLDavisMD @JDekervel @DrHarrietBK @AndresC27622123 @SValpione @KEN_K_ @FilipHerpe @SelmaAhcenedjab @Arifi34261933 @drjunaidarsh @jordanberlin5 @AnaRuizW @JafferAjaniMD @ronanhsieh @RonaYaeger @SteveMaronMD @RyanMoyMDPhD @BernabeCarolina @HardingJJMD @choong_kun @Betzabe100 @MHLars @TaberneroJosep @NataliyaUboha @KevinCSoaresMD @SunnieSKim @GABOUALFA @mdbrunocosta @TimothyJBrownMD @NajeebAl_Hallak @DrElkhoueiry @CrozrX @SKamath_MD @rprobinpark @realbowtiedoc @chase_wasson @SepideBesharati @StomachlessPA @SumeraIlyasMD @zapatalaguadomd @youngkwangchae @smitha42 @NCCN 9/23 #TumorBoardTuesday
👨🏼‍🏫Mini tweetorial 6👨🏻‍🏫
🕯️GLOW
🎲Ph3: double blind placebo-control
CLDN18.2+ (≥75% by IHC) HER2-neg unresectable/met G/GEJ
adenoca
no prior CT
📍N=507
CAPOX + Zolbe/Placebo
1° endpt: IRC-assessed PFS
2° endpt: OS, ORR, DoR, safety, PK, QoL
📚@mdmanishshah

@TumorBoardTues @MPishvaian @JohnEbbenMDPhD @KlempnerSam @CentralParkWMD @odub75 @JeremyLDavisMD @JDekervel @DrHarrietBK @AndresC27622123 @SValpione @KEN_K_ @FilipHerpe @SelmaAhcenedjab @Arifi34261933 @drjunaidarsh @jordanberlin5 @AnaRuizW @JafferAjaniMD @ronanhsieh @RonaYaeger @SteveMaronMD @RyanMoyMDPhD @BernabeCarolina @HardingJJMD @choong_kun @Betzabe100 @MHLars @TaberneroJosep @NataliyaUboha @KevinCSoaresMD @SunnieSKim @GABOUALFA @mdbrunocosta @TimothyJBrownMD @NajeebAl_Hallak @DrElkhoueiry @CrozrX @SKamath_MD @rprobinpark @realbowtiedoc @chase_wasson @SepideBesharati @StomachlessPA @SumeraIlyasMD @zapatalaguadomd @youngkwangchae @smitha42 @NCCN @mdmanishshah 10/23 #TumorBoardTuesday
👨🏼‍🏫Mini tweetorial 7👨🏻‍🏫
✨GLOW
1° endpt: mPFS 8.21 mos v 6.80 mos with zolbe v placebo
HR = 0.687
95% (CI) 0.544–0.866
P = 0.0007
🗝️2° endpt: OS (median, 14.39 mos v 12.16 mos; HR = 0.771; 95% CI, 0.615–0.965; P = 0.0118)
📚nature.com

nature.com/articles/s4159…

Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial

Nature Medicine - In the randomized, double-blind, phase 3 GLOW trial, capecitabine and oxaliplatin...

@TumorBoardTues @MPishvaian @JohnEbbenMDPhD @KlempnerSam @CentralParkWMD @odub75 @JeremyLDavisMD @JDekervel @DrHarrietBK @AndresC27622123 @SValpione @KEN_K_ @FilipHerpe @SelmaAhcenedjab @Arifi34261933 @drjunaidarsh @jordanberlin5 @AnaRuizW @JafferAjaniMD @ronanhsieh @RonaYaeger @SteveMaronMD @RyanMoyMDPhD @BernabeCarolina @HardingJJMD @choong_kun @Betzabe100 @MHLars @TaberneroJosep @NataliyaUboha @KevinCSoaresMD @SunnieSKim @GABOUALFA @mdbrunocosta @TimothyJBrownMD @NajeebAl_Hallak @DrElkhoueiry @CrozrX @SKamath_MD @rprobinpark @realbowtiedoc @chase_wasson @SepideBesharati @StomachlessPA @SumeraIlyasMD @zapatalaguadomd @youngkwangchae @smitha42 @NCCN 11/23 #TumorBoardTuesday #GastricCancer
👨🏼‍🏫Mini tweetorial 8👨🏻‍🏫
✨SPOTLIGHT
🎲Double blind placebo control
📍ph3
FOLFOX +Zolbe/placebo
1° endpt: PFS
2° endpt: OS, TTCD (GHS/QoL, PF, & QLQ-OG25-Pain score)
++ endpts: ORR, DoR, safety, PROs
📚@KoheiShitara
doi.org

doi.org/10.1016/S0140-…

Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial

Zolbetuximab, a monoclonal antibody targeting claudin-18 isoform 2 (CLDN18.2), has shown efficacy in...

@TumorBoardTues @MPishvaian @JohnEbbenMDPhD @KlempnerSam @CentralParkWMD @odub75 @JeremyLDavisMD @JDekervel @DrHarrietBK @AndresC27622123 @SValpione @KEN_K_ @FilipHerpe @SelmaAhcenedjab @Arifi34261933 @drjunaidarsh @jordanberlin5 @AnaRuizW @JafferAjaniMD @ronanhsieh @RonaYaeger @SteveMaronMD @RyanMoyMDPhD @BernabeCarolina @HardingJJMD @choong_kun @Betzabe100 @MHLars @TaberneroJosep @NataliyaUboha @KevinCSoaresMD @SunnieSKim @GABOUALFA @mdbrunocosta @TimothyJBrownMD @NajeebAl_Hallak @DrElkhoueiry @CrozrX @SKamath_MD @rprobinpark @realbowtiedoc @chase_wasson @SepideBesharati @StomachlessPA @SumeraIlyasMD @zapatalaguadomd @youngkwangchae @smitha42 @NCCN @KoheiShitara 12/23 #TumorBoardTuesday #GI23
#ASCOGI23
👨🏼‍🏫Mini tweetorial 9👨🏻‍🏫
✨SPOTLIGHT
🔹median PFS: 10·61 mos (95% CI 8·90–12·48) in zolbe v 8·67 mos (8·21–10·28) in placebo
🔸Zolbe: significant reduce in death risk v placebo (HR 0·75, 95% CI 0·60–0·94; p=0·0053)

@TumorBoardTues @MPishvaian @JohnEbbenMDPhD @KlempnerSam @CentralParkWMD @odub75 @JeremyLDavisMD @JDekervel @DrHarrietBK @AndresC27622123 @SValpione @KEN_K_ @FilipHerpe @SelmaAhcenedjab @Arifi34261933 @drjunaidarsh @jordanberlin5 @AnaRuizW @JafferAjaniMD @ronanhsieh @RonaYaeger @SteveMaronMD @RyanMoyMDPhD @BernabeCarolina @HardingJJMD @choong_kun @Betzabe100 @MHLars @TaberneroJosep @NataliyaUboha @KevinCSoaresMD @SunnieSKim @GABOUALFA @mdbrunocosta @TimothyJBrownMD @NajeebAl_Hallak @DrElkhoueiry @CrozrX @SKamath_MD @rprobinpark @realbowtiedoc @chase_wasson @SepideBesharati @StomachlessPA @SumeraIlyasMD @zapatalaguadomd @youngkwangchae @smitha42 13/23 #TumorBoardTuesday
👨🏼‍🏫Mini tweetorial 10👨🏻‍🏫
✨SPOTLIGHT
📌Safety and Tolerability of anti-CLDN18.2 mAbs
Most common AE in both studies
🤢Nausea/vomiting
🍽️anorexia
🛑TRAEs leading to drug discontinuation in 14% vs 2% in control
📚@mdmanishshah @JafferAjaniMD

@TumorBoardTues @MPishvaian @JohnEbbenMDPhD @KlempnerSam @CentralParkWMD @odub75 @JeremyLDavisMD @JDekervel @DrHarrietBK @AndresC27622123 @SValpione @KEN_K_ @FilipHerpe @SelmaAhcenedjab @Arifi34261933 @drjunaidarsh @jordanberlin5 @AnaRuizW @JafferAjaniMD @ronanhsieh @RonaYaeger @SteveMaronMD @RyanMoyMDPhD @BernabeCarolina @HardingJJMD @choong_kun @Betzabe100 @MHLars @TaberneroJosep @NataliyaUboha @KevinCSoaresMD @SunnieSKim @GABOUALFA @mdbrunocosta @TimothyJBrownMD @NajeebAl_Hallak @DrElkhoueiry @CrozrX @SKamath_MD @rprobinpark @realbowtiedoc @chase_wasson @SepideBesharati @StomachlessPA @SumeraIlyasMD @zapatalaguadomd @youngkwangchae @smitha42 @mdmanishshah 14/23 #TumorBoardTuesday
👨🏼‍🏫Mini tweetorial 11👨🏻‍🏫
✨ILUSTRO
📌Monotx/Combo with ONLY anti-PD-1
📍Ph2
cohort 1A: monotx
🔸n=30
Median PFS: 1.54mos
cohort 3A
🔸n=3
Median PFS: 2.96mos
Both ORR: 0% vs ORR 71.4% (47-88.72): same study➡️combo with FOLFOX
mPFS: 17.8 mos
📚@KlempnerSam

@TumorBoardTues @MPishvaian @JohnEbbenMDPhD @KlempnerSam @CentralParkWMD @odub75 @JeremyLDavisMD @JDekervel @DrHarrietBK @AndresC27622123 @SValpione @KEN_K_ @FilipHerpe @SelmaAhcenedjab @Arifi34261933 @drjunaidarsh @jordanberlin5 @AnaRuizW @JafferAjaniMD @ronanhsieh @RonaYaeger @SteveMaronMD @RyanMoyMDPhD @BernabeCarolina @HardingJJMD @choong_kun @Betzabe100 @MHLars @TaberneroJosep @NataliyaUboha @KevinCSoaresMD @SunnieSKim @GABOUALFA @mdbrunocosta @TimothyJBrownMD @NajeebAl_Hallak @DrElkhoueiry @CrozrX @SKamath_MD @rprobinpark @realbowtiedoc @chase_wasson @SepideBesharati @StomachlessPA @SumeraIlyasMD @zapatalaguadomd @youngkwangchae @smitha42 @mdmanishshah 15/23 #TumorBoardTuesday
Back to our case🔎
👨🏼4 cycles in study
🤢grade 2 nausea & vomiting
CEA 200 ➡️ 50
🩻CT: PR
🧪No germline or potentially actionable alterations identified on tissue NGS
💉Continued tx for 4 more cycles
🩻CT: PD
🧐What treatment would YOU suggest now?

@TumorBoardTues @MPishvaian @JohnEbbenMDPhD @KlempnerSam @CentralParkWMD @odub75 @JeremyLDavisMD @JDekervel @DrHarrietBK @AndresC27622123 @SValpione @KEN_K_ @FilipHerpe @SelmaAhcenedjab @Arifi34261933 @drjunaidarsh @jordanberlin5 @AnaRuizW @JafferAjaniMD @ronanhsieh @RonaYaeger @SteveMaronMD @RyanMoyMDPhD @BernabeCarolina @HardingJJMD @choong_kun @Betzabe100 @MHLars @TaberneroJosep @NataliyaUboha @KevinCSoaresMD @SunnieSKim @GABOUALFA @mdbrunocosta @TimothyJBrownMD @NajeebAl_Hallak @DrElkhoueiry @CrozrX @SKamath_MD @rprobinpark @realbowtiedoc @chase_wasson @SepideBesharati @StomachlessPA @SumeraIlyasMD @zapatalaguadomd @youngkwangchae @smitha42 @mdmanishshah 16/23 #TumorBoardTuesday
👨🏼‍🏫Mini tweetorial 12👨🏻‍🏫
✨Trials in 🇺🇸 targeting CLDN18.2
Different therapeutic strategies currently available
Monoclonal antibody monotherapy and in combinations
🔗clinicaltrials.gov
🔗clinicaltrials.gov
🔗clinicaltrials.gov