Idera TLR9 drug boosts Yervoy in PD-1-refractory patients

Yervoy immuno-therapy packaging
Yervoy, the Bristol-Myers Squibb drug Idera is administering with IMO-2125.

Idera Pharmaceuticals has posted early clinical data suggesting its TLR9 agonist improves outcomes in melanoma patients who progress after treatment with checkpoint inhibitors. The 44% overall response rate (ORR) in patients treated with IMO-2125 and Yervoy has emboldened Idera to move into phase 3 early next year.

IMO-2125 is designed to reactivate the anti-tumor immune response in patients whose disease has progressed following treatment with PD-1 checkpoint inhibitors such as Merck’s Keytruda and Bristol-Myers Squibb’s Opdivo. Intratumoral delivery of the TLR9 agonist does this by modulating the tumor microenvironment in a way that enables more tumor-infiltrating lymphocytes to enter cancerous sites. 

With anti-PD-1 checkpoint inhibitors establishing themselves as the standard of care in melanoma, there is an emerging opportunity for drugs that work on patients who are refractory to Keytruda and Opdivo. Idera thinks IMO-2125 can be that drug.  


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The Cambridge, Massachusetts-based biotech strengthened its case with a data drop at the European Society for Medical Oncology (ESMO) Congress. The interim phase 1 data show three of the nine patients who received 8 mg of IMO-2125—the dose Idera plans to take forward—plus Bristol-Myers’ CTLA-4 drug Yervoy had a partial response. Another patient had a complete response, resulting in an ORR of 44%. Two patients had stable disease. 

Idera’s 44% ORR is notably better than the rate achieved when Yervoy is given as a monotherapy to patients who have progressed after treatment with PD-1 checkpoint inhibitors. That has dialed up expectations for the combination therapy.

“The majority of patients with solid tumors do not respond to anti-PD-1 therapy and the published response rate to [Yervoy] alone in anti-PD-1 refractory melanoma is only 10-13%. To be seeing six out of nine patients experiencing clear disease control is extremely exciting,” MD Anderson Cancer Center’s Adi Diab, M.D., said in a statement.

The current ORR is also better than the rate achieved at the cut-off point for the ESMO abstract (PDF) submission. Back then, Idera reported one complete response, one partial response and one unconfirmed partial response. The fact one patient went from stable disease to partial response suggests the effect of IMO-2125 plus Yervoy on some people may increase over time.

Idera is now gearing up to put IMO-2125 through a bigger test. The plan is to move into phase 3 in the first quarter of next year. That is an earlier start date than anticipated by some observers. If Idera can replicate the phase 1 data in the pivotal trial, it could establish IMO-2125 as part of the go-to regimen in melanoma patients for whom PD-1 drugs are ineffective.      

IMO-2125 also has a shot at finding a place in other cancer combination therapies. Idera has seen a partial response in a less-advanced clinical trial that is testing the TLR9 agonist in combination with Keytruda.

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