Asco Plenary – pancreatic cancer, a new Kras battleground

Amgen and Mirati’s Kras inhibitors are already set for a showdown in non-small cell and colorectal cancers. The next battleground could be late-line Kras G12C-mutated pancreatic cancer, and data on Amgen’s Lumakras being presented today at the Asco Plenary Series allow a cross-trial comparison against results Mirati presented at Asco-GI last month with its rival, adagrasib. With the usual caveats about cross-trial comparisons and small patient numbers, adagrasib again looks to have the edge on efficacy, but with higher toxicity. Still, there were no deaths or treatment-related discontinuations with either asset. The next question, how big this market could be, will be top of investors’ minds after recent disappointing Lumakras sales in NSCLC. According to both Mirati and Amgen Kras G12C mutations account for just 2% of pancreatic cancers, so this looks like a very small niche. A bigger target could be Kras G12D mutants, which make up 36% of those with pancreatic cancer, Mirati reckons. The group has a G12D project, MRTX1133, in preclinical development.

Cross-trial comparison of Lumakras vs adagrasib in Kras G12C-mutant pancreatic cancer
Product/ project Company Trial Cut-off date N ORR Median PFS TRAEs Grade ≥3 TRAEs 
Lumakras Amgen Ph1/2 Codebreak-100 Nov 1, 2021 38 21% 4.0mth 42% 16%
Adagrasib Mirati Ph1/2 Krystal-1 Sep 10, 2021 10* 50%** 6.6mth 87%*** 27%***
*Pts had pancreatic ductal adenocarcinoma, which accounts for >90% of pancreatic cancers; **Includes 1 unconfirmed PR; ***Analysis includes 30 pts with GI cancers. ORR=objective response rate; TRAE=treatment-related adverse events. Source: Asco Plenary & Asco-GI.

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