ASCO-GI – Jacobio’s KRAS looks competitive in pancreatic
There has been much activity in KRAS G12C inhibition, but progress in pancreatic cancer has been slow. Jacobio could challenge more established players in this setting, if data released in an ASCO-GI abstract are anything to go by. The group’s glecirasib looks competitive versus Mirati’s Krazati and Amgen’s Lumakras, with the usual caveats about cross-trial comparisons. Notably, the result with glecirasib came from a pooled analysis of two trials in KRAS G12C-mutated solid tumours, one carried out in China. A phase 2 study in pancreatic cancer, also in China, has yet to start enrolling, according to clinicaltrials.gov. Mirati’s Krazati was previously the project to beat here, the table below shows. An investigator-sponsored phase 1 study is recruiting, and the group had promised an update on its pancreatic filing strategy by year-end, but in the meantime was acquired by Bristol Myers Squibb. Meanwhile, a pancreatic cancer trial of Lumakras has been withdrawn. The other competitor of note here is Revolution Medicines, which reported an ORR of 20% in pancreatic cancer with its multi-RAS inhibitor RMC-6236 at ESMO 2023; however, this study excluded G12C mutants. Revolution is planning a phase 3 trial in second-line pancreatic cancer that could start this year.
Cross-trial comparison of Kras G12C inhibitors in pancreatic cancer
Glecirasib | Krazati | Lumakras | |
---|---|---|---|
Company | Jacobio Pharmaceuticals | Mirati | Amgen |
Trial | 2 pooled ph1/2s (NCT05009329 & NCT05002270) | Ph1/2 Krystal-1 | Ph 1/2 Codebreak-100 |
Source | ASCO-GI 2024 abstract | Journal of Clinical Oncology, Apr 2023 | ASCO plenary, Feb 2022 |
Cut-off date | 8 Sep 2023 | 1 Oct 2022 | 1 Nov 2021 |
N | 28 | 21 | 38 |
ORR | 46% | 33% | 21% |
mPFS | 5.5 months | 5.4 months | 4.0 months |
TRAEs | 90%* | 97%** | 42% |
Grade ≥3 TRAEs | 25%* | 27%** | 16% |
*Among 48 pts with various tumour types; **Among 57 pts with various tumour types. Source: OncologyPipeline.
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