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@OncoAlert #ASCO2020 In addition to the outstanding GI abstracts, there will be many presentations and posters adding to the wealth of data that demonstrate that a real percentage of almost all tumors types harbor actionable molecular alterations.

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@OncoAlert Key presentations at #ASCO2020 will broaden the # of actionable targets with meaningful Txs associated with a clinical benefit, including FGFR, RET, KRASG12C, HRD, PIK3CA, and even biomarkers for IO.

So here are my Top 10 Targeted Tx Abstracts

3/ HER2
1) Trastuzumab deruxtecan (T-DXd; DS-8201) is trastuzumab with a TOP1-inh payload
Sienna et al, DESTINY-CRC01 Abs# 4000
CRC, all patients had prior irinotecan!
ORR was 45.3% (1 CR, 23 PRs; median DOR NR)
EVEN pts w/ prior anti-HER2 Tx – ORR was 44%
mPFS 6.9 mo; mOS NR

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2) HER2 - Gastric/GE Jxn
Shitara, DESTINY-Gastric01 #4513
R-Ph II trial of T-DXd vs. PC(irino or paclitaxel)
All patients had prior anti-HER2 Tx
ORR was 51% vs. 14%
DOR 11.3 vs. 3.9 mo
mPFS 5.6 vs. 3.5 mo
mOS 12.5 vs. 8.4 mo
All sig
New SOC for HER2+ G/GE cancers >=2nd line?

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3) Biomarkers predictive of immuncheckpoint (ICIs)
Brown, #3007 - LRP1B alterations
Tumors w/ path LRP1B alterations vs non-path mut in patients Txed with ICIs
ORR 57% vs. 18%
EVEN excluding MSIH or TMBH tumors, ORR 56% vs. 17%
Path LRP1B alterations greater PFS and OS

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4) Biomarkers predictive of immuncheckpoint (ICIs) #2
Garmezy, #3008
For patients with pathogenic POLE mutations Txed with ICI
ORR 31% - not explained by underlying MSIH status

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5) FGFR
Goyal, et al, FOENIX-CCA2, Abs #108 - Futibatinib for pts with intrahepatic cholangiocarcinoma harboring FGFR2 gene fusions (81% of pts) or other rearrangements.
ORR = 34%, median DOR 6.2 months

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6) RET
The truly great @VivekSubbiah et al, Abs #109
RET inhibitor pralsetinib (BLU-667) in patients with RET fusion+ solid tumors.
Thyroid cancer: ORR = 75%, median DOR 14.5 mos
All other cancers: ORR = 60%
WOW!!!

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KRASG12C
7) CodeBreak 100: AMG 510 (KRASG12C inh)
Hong, #3511 (NOT NSCLC or CRC)
Included 10 #pancreaticcancer pts
3 PRs and 13 SD/22 pts
(6 PDAC pts had SD, no PRs)

8) CodeBreak 100: AMG 510 for CRC
Fakih, #4018
42 patients, ORR only 7%, but DCR = 76%

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9) HRD
Dhawan, #3513
Ph I rucaparib + irinotecan in pts with HRD mutated tumors

Pulse dosed rucaparib + irinotecan
3 DLTs, all neutropenia
1/13 PR, but 5/13 on Tx for at least 3 months, and 3 patients with ATM mutations on Tx for >1 year

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10) PIK3CA
Damodaran, #3506
Ph II of copanlisib in patients with tumors with PIK3CA mutations (PTEN loss allowed): NCI MATCH EAY131-Z1F.
28 pts
ORR = 11% (3//28), with 6 pts with SD > 6 months