Thread by @KlempnerSam

@TumorBoardTues 1/15 #TumorBoardTuesday #GastricCancer #OncTwitter
Here goes

🎬Starting out with an overall poll Q

When a new advanced GC/GEJ patient presents to your clinic, your institution reflexively tests for which of the following?

@TumorBoardTues 2/15 #TumorBoardTuesday

68y/o with poorly diff gastric cardia adeno, diffuse LAD, +peritoneal mets.

🧬Biomarkers HER2-, PD-L1-, MSS
🧪Pre-screened for trials & FGFR2b-, Claudin18.2+
🔦Enrolls in frontline SPOTLIGHT trial.

❓What is Claudin18.2?
❓What is SPOTLIGHT?

@TumorBoardTues 3/15 #TumorBoardTuesday

✨Claudin18.2 (CLDN18.2)✨

Transmembrane protein typically present in tight junctions of gastric mucosal cells, maintains barrier function of gastric mucosa, & prevents leakage of H+ in gastric acid through paracellular pathways.

@TumorBoardTues ✨Claudin18.2 (CLDN18.2)✨

🧑Patient: You’re doing all of these tests. What cancers express CLDN18.2?

🤝 #SharedDecision

🩺 clinician: Great question

1️⃣ Gastric/GEJ
2️⃣ Pancreatic
3️⃣ Biliary Tract, #NSCLC, Ovarian (less common)

@TumorBoardTues 5/15 #TumorBoardTuesday
✨Claudin18.2 (CLDN18.2)✨

🧑: OK, but is CLDN18.2 rare like NTRK fusions, etc?

🩺: No, prevalence varies by IHC cutoff and IHC assay but…

📍Gastric/GEJ/EAC: ~28-40% of patients are CLDN18.2+ and seen in diffuse and intestinal type #GastricCancer

@TumorBoardTues 6/15 #TumorBoardTuesday #GastricCancer
✨Claudin18.2 (CLDN18.2)✨

🧑: 🆒 So does it overlap with other GC/GEJ/EAC biomarkers?

🩺: uuuuuhhhh, we are working on it. With a prevalence of >30% for CLDN18.2+ there is some overlap

@TumorBoardTues 7/15 #TumorBoardTuesday
✨Claudin18.2 (CLDN18.2)✨

Here’s early papers on CLDN18.2 overlap
1. CLDN18.2+ TME: rdcu.be/c0Wbw
2. CLDN18.2 Landscape review: rdcu.be/c0Wbt
3. CLDN18.2 Biomarker: mdpi.com/1330386

@TumorBoardTues 8/15 #TumorBoardTuesday #GastricCancer
✨Claudin18.2 (CLDN18.2)✨

🧑: It seems like a tumor-restricted 🎯 target — does that make it amenable to different treatment approaches?

🩺: Yes, several strategies beyond Zolbetuximab are being explored. Here are some examples👇🏽

@TumorBoardTues @KoheiShitara @YJanjigianMD @mdmanishshah @ILSONDavid @JafferAjaniMD @JeeyunM @SteveMaronMD @RyanMoyMDPhD @SunnieSKim @rutikamehtaMD @NataliyaUboha @HaeseongPark1 @mgibson21212 @Dr_AfsanehBarzi @LFonkoua @FlorianLordick @LizzySmyth1 @FilippoPietran4 @ElisaFontana83

@TumorBoardTues @KoheiShitara @YJanjigianMD @mdmanishshah @ILSONDavid @JafferAjaniMD @JeeyunM @SteveMaronMD @RyanMoyMDPhD @SunnieSKim @rutikamehtaMD @NataliyaUboha @HaeseongPark1 @mgibson21212 @Dr_AfsanehBarzi @LFonkoua @FlorianLordick @LizzySmyth1 @FilippoPietran4 @ElisaFontana83 9/15 #TumorBoardTuesday #GastricCancer

✨ SPOTLIGHT✨

🧑: Got it, I am trying to picture the design of this phase III 🔦 SPOTLIGHT trial, can you remind me?

🩺: Of course, may be easiest to draw it out 👇🏽

@TumorBoardTues @KoheiShitara @YJanjigianMD @mdmanishshah @ILSONDavid @JafferAjaniMD @JeeyunM @SteveMaronMD @RyanMoyMDPhD @SunnieSKim @rutikamehtaMD @NataliyaUboha @HaeseongPark1 @mgibson21212 @Dr_AfsanehBarzi @LFonkoua @FlorianLordick @LizzySmyth1 @FilippoPietran4 @ElisaFontana83 10/15 #TumorBoardTuesday
✨ SPOTLIGHT✨

🧑: Before I sign onto this phase III 🔦SPOTLIGHT, what do we know about Zolbetuximab in patients?

🩺: Zolbetuximab has been studied as monotherapy, in combination with frontline chemotherapy, and in combination with anti-PD-1

@TumorBoardTues @KoheiShitara @YJanjigianMD @mdmanishshah @ILSONDavid @JafferAjaniMD @JeeyunM @SteveMaronMD @RyanMoyMDPhD @SunnieSKim @rutikamehtaMD @NataliyaUboha @HaeseongPark1 @mgibson21212 @Dr_AfsanehBarzi @LFonkoua @FlorianLordick @LizzySmyth1 @FilippoPietran4 @ElisaFontana83 @jeremyldavismd @jdekervel @drharrietbk @andresc27622123 @svalpione @juanmaoconnor @ken_k_ @filipherpe @selmaahcenedjab @arifi34261933 @gervasolorenzo @gillsharlene @odub75 @postoronnie_ @thalcin @nvijayvergiamd @drjunaidarsh @jordanberlin5 @anaruizw @shosatomd1 @ajacomemd

@TumorBoardTues @KoheiShitara @YJanjigianMD @mdmanishshah @ILSONDavid @JafferAjaniMD @JeeyunM @SteveMaronMD @RyanMoyMDPhD @SunnieSKim @rutikamehtaMD @NataliyaUboha @HaeseongPark1 @mgibson21212 @Dr_AfsanehBarzi @LFonkoua @FlorianLordick @LizzySmyth1 @FilippoPietran4 @ElisaFontana83 @JeremyLDavisMD @JDekervel @DrHarrietBK @AndresC27622123 @SValpione @Juanmaoconnor @KEN_K_ @FilipHerpe @SelmaAhcenedjab @Arifi34261933 @GervasoLorenzo @GillSharlene @odub75 @postoronnie_ @Thalcin @NVijayvergiaMD @drjunaidarsh @jordanberlin5 @AnaRuizW @ShoSatoMD1 @AJacomeMD 11/15 #TumorBoardTuesday

1️⃣MONO Ph2(Zolbe): ORR 14% in CLDN18.2 high @Annals_Oncology
📚pubmed.ncbi.nlm.nih.gov/31240302/
2️⃣FAST Ph2 (EOX +/- Zolbe):⬆️PFS & OS in CLDN18.2+,⬆️in higher CLDN18.2
📚pubmed.ncbi.nlm.nih.gov/33610734/
3️⃣ILUSTRO: FOLFOX + Zolbe cohort ORR 63%

@TumorBoardTues @KoheiShitara @YJanjigianMD @mdmanishshah @ILSONDavid @JafferAjaniMD @JeeyunM @SteveMaronMD @RyanMoyMDPhD @SunnieSKim @rutikamehtaMD @NataliyaUboha @HaeseongPark1 @mgibson21212 @Dr_AfsanehBarzi @LFonkoua @FlorianLordick @LizzySmyth1 @FilippoPietran4 @ElisaFontana83 @JeremyLDavisMD @JDekervel @DrHarrietBK @AndresC27622123 @SValpione @Juanmaoconnor @KEN_K_ @FilipHerpe @SelmaAhcenedjab @Arifi34261933 @GervasoLorenzo @GillSharlene @odub75 @postoronnie_ @Thalcin @NVijayvergiaMD @drjunaidarsh @jordanberlin5 @AnaRuizW @ShoSatoMD1 @AJacomeMD @Annals_Oncology 12/15 #TumorBoardTuesday #GastricCancer

🧑: Tell me about safety/toxicity/QoL for chemo combo

🩺: Important question.

Some common AEs
🤢Nausea
🤮Vomiting
🦵💦some peripheral edema
QoL/PRO favored Zolbetuximab arm in FAST⬇️

📚PRO from FAST trial pubmed.ncbi.nlm.nih.gov/33755863/

@TumorBoardTues @KoheiShitara @YJanjigianMD @mdmanishshah @ILSONDavid @JafferAjaniMD @JeeyunM @SteveMaronMD @RyanMoyMDPhD @SunnieSKim @rutikamehtaMD @NataliyaUboha @HaeseongPark1 @mgibson21212 @Dr_AfsanehBarzi @LFonkoua @FlorianLordick @LizzySmyth1 @FilippoPietran4 @ElisaFontana83 @JeremyLDavisMD @JDekervel @DrHarrietBK @AndresC27622123 @SValpione @Juanmaoconnor @KEN_K_ @FilipHerpe @SelmaAhcenedjab @Arifi34261933 @GervasoLorenzo @GillSharlene @odub75 @postoronnie_ @Thalcin @NVijayvergiaMD @drjunaidarsh @jordanberlin5 @AnaRuizW @ShoSatoMD1 13/15 #TumorBoardTuesday
🧑: What should we call FOLFOX + Zolbetuximab regimen?

🩺: I like this game. Maybe Z-FOX or ChemoZ?

Let’s ask @KoheiShitara @YJanjigianMD @mdmanishshah @ILSONDavid @JafferAjaniMD @JeeyunM @rutikamehtaMD @FlorianLordick @LizzySmyth1 @FilippoPietran4

@TumorBoardTues @KoheiShitara @YJanjigianMD @mdmanishshah @ILSONDavid @JafferAjaniMD @JeeyunM @SteveMaronMD @RyanMoyMDPhD @SunnieSKim @rutikamehtaMD @NataliyaUboha @HaeseongPark1 @mgibson21212 @Dr_AfsanehBarzi @LFonkoua @FlorianLordick @LizzySmyth1 @FilippoPietran4 @ElisaFontana83 @JeremyLDavisMD @JDekervel @DrHarrietBK @AndresC27622123 @SValpione @Juanmaoconnor @KEN_K_ @FilipHerpe @SelmaAhcenedjab @Arifi34261933 @GervasoLorenzo @GillSharlene @odub75 @postoronnie_ @Thalcin @NVijayvergiaMD @drjunaidarsh @jordanberlin5 @AnaRuizW @ShoSatoMD1 14/15 #TumorBoardTuesday

Why did Astellas give their trials a 💡🔦 theme?

🔦SPOTLIGHT: Ph III of FOLFOX + Zolbe/Placebo
🕯️GLOW: Ph III CAPOX + Zolbe/Placebo
💡ILUSTRO: Ph II of Zolbe combos (FOLFOX + Zolbe + nivo, etc)

Answer: No idea 🤷‍♀️🤷🤷‍♂️

@TumorBoardTues @KoheiShitara @YJanjigianMD @mdmanishshah @ILSONDavid @JafferAjaniMD @JeeyunM @SteveMaronMD @RyanMoyMDPhD @SunnieSKim @rutikamehtaMD @NataliyaUboha @HaeseongPark1 @mgibson21212 @Dr_AfsanehBarzi @LFonkoua @FlorianLordick @LizzySmyth1 @FilippoPietran4 @ElisaFontana83 @JeremyLDavisMD @JDekervel @DrHarrietBK @AndresC27622123 @SValpione @Juanmaoconnor @KEN_K_ @FilipHerpe @SelmaAhcenedjab @Arifi34261933 @GervasoLorenzo @GillSharlene @odub75 @postoronnie_ @Thalcin @NVijayvergiaMD @drjunaidarsh @jordanberlin5 @AnaRuizW @ShoSatoMD1 15/15 #TumorBoardTuesday

🧑: I've been on this trial for awhile, when will we know the full results?

🩺: Enrollment is completed in 🔦SPOTLIGHT & 🕯️GLOW phase III trials. We just saw topline results that 🔦SPOTLIGHT is ➕ for PFS (primary) & OS

📚cancernetwork.com/view/zolbetuxi…

@TumorBoardTues @KoheiShitara @YJanjigianMD @mdmanishshah @ILSONDavid @JafferAjaniMD @JeeyunM @SteveMaronMD @RyanMoyMDPhD @SunnieSKim @rutikamehtaMD @NataliyaUboha @HaeseongPark1 @mgibson21212 @Dr_AfsanehBarzi @LFonkoua @FlorianLordick @LizzySmyth1 @FilippoPietran4 @ElisaFontana83 @JeremyLDavisMD @JDekervel @DrHarrietBK @AndresC27622123 @SValpione @Juanmaoconnor @KEN_K_ @FilipHerpe @SelmaAhcenedjab @Arifi34261933 @GervasoLorenzo @GillSharlene @odub75 @postoronnie_ @Thalcin @NVijayvergiaMD @drjunaidarsh @jordanberlin5 @AnaRuizW @ShoSatoMD1 #PostTest Q1️⃣ #TumorBoardTuesday
👉🏽#CME Eval 🔗 integrityce.com/tbtEval

🤔@KlempnerSam taught us a ⛴️-load, test your 🧠 with 3 quick Q’s

@TumorBoardTues @KoheiShitara @YJanjigianMD @mdmanishshah @ILSONDavid @JafferAjaniMD @JeeyunM @SteveMaronMD @RyanMoyMDPhD @SunnieSKim @rutikamehtaMD @NataliyaUboha @HaeseongPark1 @mgibson21212 @Dr_AfsanehBarzi @LFonkoua @FlorianLordick @LizzySmyth1 @FilippoPietran4 @ElisaFontana83 @JeremyLDavisMD @JDekervel @DrHarrietBK @AndresC27622123 @SValpione @Juanmaoconnor @KEN_K_ @FilipHerpe @SelmaAhcenedjab @Arifi34261933 @GervasoLorenzo @GillSharlene @odub75 @postoronnie_ @Thalcin @NVijayvergiaMD @drjunaidarsh @jordanberlin5 @AnaRuizW @ShoSatoMD1 🧐 Which are true of the Zolbetuximab containing arm of phase II FAST trial for chemotherapy +/- Zolbetuximab in advanced GC/GEJ patients?

@TumorBoardTues @KoheiShitara @YJanjigianMD @mdmanishshah @ILSONDavid @JafferAjaniMD @JeeyunM @SteveMaronMD @RyanMoyMDPhD @SunnieSKim @rutikamehtaMD @NataliyaUboha @HaeseongPark1 @mgibson21212 @Dr_AfsanehBarzi @LFonkoua @FlorianLordick @LizzySmyth1 @FilippoPietran4 @ElisaFontana83 @JeremyLDavisMD @JDekervel @DrHarrietBK @AndresC27622123 @SValpione @Juanmaoconnor @KEN_K_ @FilipHerpe @SelmaAhcenedjab @Arifi34261933 @GervasoLorenzo @GillSharlene @odub75 @postoronnie_ @Thalcin @NVijayvergiaMD @drjunaidarsh @jordanberlin5 @AnaRuizW @ShoSatoMD1 #PostTest Q 2️⃣ #TumorBoardTuesday
👉🏽 Free #CME (AMA & MOC)🔗 integrityce.com/tbt

🧐 A patient presents to your clinic with dx advanced #GastricCancer. How is CLDN18.2 tested?

@TumorBoardTues @KoheiShitara @YJanjigianMD @mdmanishshah @ILSONDavid @JafferAjaniMD @JeeyunM @SteveMaronMD @RyanMoyMDPhD @SunnieSKim @rutikamehtaMD @NataliyaUboha @HaeseongPark1 @mgibson21212 @Dr_AfsanehBarzi @LFonkoua @FlorianLordick @LizzySmyth1 @FilippoPietran4 @ElisaFontana83 @JeremyLDavisMD @JDekervel @DrHarrietBK @AndresC27622123 @SValpione @Juanmaoconnor @KEN_K_ @FilipHerpe @SelmaAhcenedjab @Arifi34261933 @GervasoLorenzo @GillSharlene @odub75 @postoronnie_ @Thalcin @NVijayvergiaMD @drjunaidarsh @jordanberlin5 @AnaRuizW @ShoSatoMD1 #PostTest Q 3️⃣ #TumorBoardTuesday
👉🏽#CME eval (AMA & MOC)🔗 integrityce.com/tbteval

🧐 What is the expected prevalence of Claudin 18.2-high (CLDN18.2-high) in advanced #GastricCancer/GEJ cancers