Checkmate Pharmaceuticals reports early-stage data on potential of CMP-001 to treat patients resistant to PD-1 inhibitors

Checkmate Pharmaceuticals on Tuesday reported data from a Phase Ib study showing that the experimental TLR9 agonist CMP-001 induced durable clinical responses in combination with Merck & Co.'s Keytruda (pembrolizumab) in patients with advanced melanoma resistant to prior anti-PD-1 checkpoint inhibition. Results presented at the American Association of Cancer Research (AACR) demonstrated that the combination regimen achieved an objective response rate of 22 percent. Checkmate CEO Art Krieg noted "the duration of response, which is ongoing in most of the responders, is particularly encouraging and supports further clinical development of CMP-001."  

In the ongoing study, 85 patients with PD-1-resistant advanced melanoma have received CMP-001 in combination with Keytruda. The intent-to-treat population consists of 69 patients, including 44 patients in the dose escalation phase and 25 patients in the dose expansion phase, who have received at least one dose of CMP-001 and completed at least one follow-up scan or discontinued treatment prior to the scan.  

Checkmate noted that the primary endpoint of the study is identifying the recommended Phase II dose of CMP-001 in patients with advanced melanoma that is resistant to PD-1 inhibition. Meanwhile, secondary endpoints include assessments of the safety profile of the combination regimen and its effects on serum CXCL10 concentrations.  

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The population of responders included two patients with complete responses and 13 patients with partial responses. Of these, response has been maintained in six patients for more than six months, while the median duration of response has not been reached. In addition, three additional patients who continued treatment beyond their initial progression were later identified as responders.  

Principal investigator Mohammed Milhem remarked "based on these preliminary findings, the combination of CMP-001 and [Keytruda] appears to have a manageable safety profile and meaningful clinical activity," continuing "additional larger studies in this patient population will need to be conducted to further evaluate the clinical benefit, but if the current results are confirmed, it appears that this combination could offer a new treatment option for patients with advanced melanoma who are not responsive to [Keytruda]."

Checkmate described CMP-001 as a "first in class CpG-A TLR9 agonist that is encapsulated in a virus-like particle." The drugmaker explained that the treatment is designed to activate innate immunity to convert anti-PD-1 therapy-unresponsive tumours into lesions that respond to PD-1 inhibition. 

For related analysis, see ViewPoints: Stronger immune responses make Checkmate Pharmaceuticals and checkpoint inhibitors a winning combination.


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