Thread by @MPishvaian

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#ASCO22 Biomarker Recap

😀Don't know about you all - but I had a great time at the meeting this year!

👉I will🔦a few biomarker based studies that caught my👁️

😉Did you notice that TWO of the plenary abstracts were for biomarker based trials‼️

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#1⃣
✅Dr. Yoshino🧑‍🏫the results of the Ph 3 PARADIGM trial
➡️FOLFOX-Pani vs. FOLFOX-Bev for RAS WT left CRC
👉823 Pts

👏OS>with Pani 36.2 vs. 31.3 months
👏ORR also > with Pani 75% vs. 67%

🤔BUT the curves don't separate until 26 months❓

🔎Abstract #LBA1

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#2⃣

✅Dr. Modi🧑‍🏫the results of the Ph 3 DESTINY-Breast04 trial
➡️T-DXd vs. SOC for HER-2 low metBreast Ca
👉557 Pts

👏PFS>with T-DXd 10.1 vs. 5.4 months
👏OS also > with T-DXd 23.9 vs. 17.5 months

🔎Abstract #LBA3

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These are clearly two practice modifying abstracts:
👉Use an anti-EGFR + chemo front line for a RAS/RAF WT met CRC
👉T-DXd is better than standard chemo in HER-2 low breast cancer

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#3⃣

(I missed this in the pre-review)
✅Alison Schram🧑‍🏫a trial of zenocutuzumab, a HER2 x HER3 bispecific Ab for NRG1 fusion+ Ca
👉73 assessable Pts
👉Mostly NSCLC & PDAC

ORR = 34% (42% in PDAC)
Median duration of response = 9.1 months

🔎Abstract #105

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But in fairness...
✅Daniel R. Carrizosa🧑‍🏫a trial of seribantumab, an anti-HER3 mAb in NRG1 fusion+ Ca
👉Only 10 assessable Pts
👉3/10 responded

➡️So this appears to be a class effect

🔎Abstract #3006

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#4⃣

👇HER3 is a legitimate target
✅Ian E. Krop🧑‍🏫a Ph1/2 trial of patritumab deruxtecan, a HER3-directed ADC in pts with HER3 expressing Breast Ca

👏Out of 113 patients, the ORR was 30%

🔎Abstract # 1002

🤔I don't see a follow up Ph2 or Ph3 study though?

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HER3 is also a🎯in Lung Ca
✅Dr. Steur👨‍🏫Ph1 trial of Patritumab deruxtecan in NSCLC
😮BUT the predictor was NOT⬆️HER3
➡️It was a driver🧬alteration
👉e.g. K/NRAS/EGFR/ROS/ALK
➡️ORR in the driver group = 35%
🔎Abstract 9017

AND - several F/U trials in Lung Ca

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#6⃣

✅@PamelaKunzMD 🧑‍🏫the final analysis of Cap-Tem in pancreatic neuroendocrine tumors
👉97 patients with MGMT testing available

👏⬆️ORR if MGMT absent:
➡️MGMT Low>High 33% vs. 15%
➡️MGMT Promoter Meth (+) > (-) 86% vs. 38%

🔎Abstract # 4004

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#7

✅@hoperugo & @stolaney1 🧑‍🏫a randomized Ph3 trial of the Trop-2 directed ADC, sacituzumab govitecan (SG) vs SOC for Breast Ca
👉543 Pts

👏mPFS> with SG over SOC 5.5 vs. 4.0 months
🤔BUT...SG was more toxic🤢

🔎# LBA1001

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#8

🔥Important updates on🎯KRASG12C-mutated cancers
✅Dr. Spira🧑‍🏫a Ph1/2 trial of adagrasib in KRASG12C-mutated NSCLC
➡️ORR in 116 patients=43%

🔎Abstract 9002

🙏PLEASE check for this mutation in your patients

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#9

🔥Claudin 18.2 has become a “hot”🎯
👉Two abstracts

✅Dr. Huang 🧑‍🏫13 pts Tx w/MIL93, an anti-Claudin18.2 mAb
➡️1⃣pt w/ a PR, 3 w/ SD
🔎Abstract 3086

✅Dr. Gong🧑‍🏫Ph1 trial of Q-1802, a Claudin18.2/PD-L1 bsAB
➡️ORR 1⃣/9⃣pts
🔎Abstract 2568

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#10

🔥MDM2i are showing real promise
👉2 abstracts

✅Dr. McKean🧑‍🏫a Ph2 trial of alrizomadlin (APG-115)➕pembro
➡️ORR=24%
➡️40% in MPNST
🔎Abstract 9517

✅Dr. Dumbrava🧑‍🏫a Ph2 trial IN PROGRESS of milademetan (MANTRA-2)
➡️Stay tuned....

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#11

🥁And last but definitely not least
👉Two novel HER2🎯therapies

✅Dr. Sheng 🧑‍🏫a novel HER2 ADC where the “drug” payload is an anti-PD-1 IgG4
➡️41 bladder Ca pts
➡️ORR=83%
➡️ORR=50% even in HER2 Lo/Neg pts
🔎Abstract 4518

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✅@KReissMD🧑‍🏫an exciting new agent, CT-0508
➡️This is a first in class CAR-M, comprised of autologous monocyte derived macrophages expressing an anti-HER2 CAR
➡️ The abstract results were very early, but very intriguing
🔎Abstract 2533

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I hope you all enjoyed this summary

If anyone wants to report on the exciting abstracts at World GI - let me know 😉