I think we might want to add GSK to the list of potential partners. Their ICI Jemperli (dostarlimab) made waves a few years ago when 12 out of 12 patients with mismatch repair deficient (dMMR) CRC had no evidence of disease after a trial. They got a BTD for that, and are in a pivotal Phase 2 trial to confirm results. I asked Google AI--
"Is GSK conducting trials with dostarlimab in MSS mCRC? With other drugs?"
Very interesting response:
"Yes, GSK is actively testing dostarlimab in combination with other drugs for MSS/pMMR mCRC, which is notoriously resistant to ICIs alone. The primary focus of these trials is to convert "cold" (immune resistant) MSS tumors into "hot" (immune responsive) tumors, often using neoadjuvant approaches to shrink tumors before surgery."
Several of these combo trials involve their investigational PARP inhibitor niraparib, which boosts PDL-1 by activating the cGAS/STING pathway and promoting IFN signaling. (Doesn't come close to what leronlimab can do, however, based on the limited efficacy in clinical trials. In endometrial cancer, for example, the combo had a 14% ORR). They also are exploring combinations involving chemo and a TIM-3 inhibitor, without compelling results.
So, GSK is trying hard to turn cold tumors hot... but not really succeeding. They got a taste of what it feels like to dominate the competition in a small subset of mCRC patients with their 100% Complete Response Rate in that earlier trial (with dMMR patients)... Why not aspire towards a 100% Complete Response Rate in the much larger MSS-mCRC indication by doing a deal with Cytodyn? The potential to offer basically a cure for a notoriously hard-to-treat cancer--with a huge addressable market that is increasingly affecting younger patients--would do wonders for the GSK brand, and vault them into the forefront of the cancer-killers (along with Cytodyn, of course). They are also testing Jemperli in mTNBC... And they have the financial muscle and clinical chops to develop leronlimab post-haste.
I'd say GSK should make the cut, and join MRK, BMS, and Merck KGaA on the short list of potential partners. Let the bidding begin! Write down a number on the index card provided, and pass it forward...
"Is GSK conducting trials with dostarlimab in MSS mCRC? With other drugs?"
Very interesting response:
"Yes, GSK is actively testing dostarlimab in combination with other drugs for MSS/pMMR mCRC, which is notoriously resistant to ICIs alone. The primary focus of these trials is to convert "cold" (immune resistant) MSS tumors into "hot" (immune responsive) tumors, often using neoadjuvant approaches to shrink tumors before surgery."
Several of these combo trials involve their investigational PARP inhibitor niraparib, which boosts PDL-1 by activating the cGAS/STING pathway and promoting IFN signaling. (Doesn't come close to what leronlimab can do, however, based on the limited efficacy in clinical trials. In endometrial cancer, for example, the combo had a 14% ORR). They also are exploring combinations involving chemo and a TIM-3 inhibitor, without compelling results.
So, GSK is trying hard to turn cold tumors hot... but not really succeeding. They got a taste of what it feels like to dominate the competition in a small subset of mCRC patients with their 100% Complete Response Rate in that earlier trial (with dMMR patients)... Why not aspire towards a 100% Complete Response Rate in the much larger MSS-mCRC indication by doing a deal with Cytodyn? The potential to offer basically a cure for a notoriously hard-to-treat cancer--with a huge addressable market that is increasingly affecting younger patients--would do wonders for the GSK brand, and vault them into the forefront of the cancer-killers (along with Cytodyn, of course). They are also testing Jemperli in mTNBC... And they have the financial muscle and clinical chops to develop leronlimab post-haste.
I'd say GSK should make the cut, and join MRK, BMS, and Merck KGaA on the short list of potential partners. Let the bidding begin! Write down a number on the index card provided, and pass it forward...
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