Oncolytics Biotech Inc T.ONC

RE:G12D/G12V KRAS mutation in PC & CRC patients respond to Pela

[Noteable]

September 25, 2024 - An attempt by Merck & Co. to unlock the microsatellite stable (MSS) metastatic colorectal cancer market has ended in failure.  a fixed-dose combination of Keytruda and an anti-LAG-3 antibody failed to improve overall survival.

An earlier colorectal cancer study supported full FDA approval of Keytruda in people with microsatellite instability-high solid tumors. MSS colorectal cancer, the most common form of the disease, has proven a tougher nut to crack, with checkpoint inhibitors with sub-10% response rates as single agents.

https://www.fiercebiotech.com/biotech/mercks-keytruda-lag-3-combo-fails-tame-tough-colorectal-cancer-phase-3

In 2021  Sanjay Goel, et al. found for the first time that immune-insensitive MSS tumors that account for 85% of all CRC can be effectively converted to immunotherapy-sensitive cancers by introducing reovirus to the therapeutic regimen.


May 2024 -  The Efficacy of Immune Checkpoint Inhibitors in Microsatellite Stable Colorectal Cancer:


 while ICI monotherapy has limited efficacy in MSS CRC, combination strategies hold promise to enhance survival outcomes

In 2021 Titto Augustine, Sanjay Goel, et al. found for the first time that immune-insensitive MSS tumors that account for 85% of all CRC can be effectively converted to immunotherapy-sensitive cancers by introducing reovirus to the therapeutic regimen. They reported that their data confidently establishes that reovirus sensitizes MSS tumors to anti-PD-1 therapy via increasing the expression of PD-L1 marker on respective target cells. 

 

Combinatorial treatment activated the innate immune system, pattern recognition receptors, and antigen presentation markers. Furthermore, the investigators observed the reduction of immunosuppressive macrophages and expansion of effector T cell subsets, as well as reduction in T cell exhaustion. The current investigation sheds light on the immunological mechanisms of the reovirus-anti-PD-1 combination to reduce the growth of MSS CRC. 

https://academic.oup.com/oncolo/article/29/5/e580/7600404