I find it amazing how rapidly immune-oncology drugs work, and how quickly they can tell if they are working or not. The ORR is an appropriate and smart choice for an endpoint for our mCRC trial, but in terms of tracking response and endpoints, ctDNA measurements look like they are the future. This is from an article in Targeted Oncology. It's from December, so perhaps it's common knowledge, but I hadn't seen it:
"Changes in ctDNA levels measured as early as 3 weeks after treatment initiation were highly predictive of long-term outcomes. A molecular response (ctDNA-mR), defined as a ≥ 30% decrease in ctDNA, strongly correlated with improved progression-free survival (PFS) and overall survival (OS).
In the retrospective cohort, patients who achieved ctDNA-mR (≥ 30% reduction) had significantly better PFS (HR, 2.69) and OS (HR, 2.23) compared with non-mR patients. In the validation cohort, the hazard ratios were 2.14 for PFS and 2.56 for OS.
Failure to achieve mR demonstrated a positive predictive value of 100% for identifying non-responders. Conversely, 100% of patients who achieved a complete or partial response by imaging had a ctDNA decrease at the pre-C2 timepoint."
(The pre-C2 timepoint they mention--which stands for Cycle 2--refers to the blood sample collected right before the administration of the second dose of immunotherapy. That is usually 3 to 4 weeks after the first dose. Quick!
https://www.targetedonc.com/view/ctdna-assay-...id-tumors#
30% seems to be the magic number for responders when measured by imaging or ctDNA count. Since ORR numbers are still going to be important in the mCRC trial, I dug up the standard RECIST guidelines (Response Evaluation Criteria in Solid Tumors, for those, like me, who didn't know what the acronym meant):
PARTIAL RESPONSE--30% or greater decrease in the sum of diameters of target lesions (up to five measurements to account for irregular tumors).
COMPLETE RESPONSE--Disappearance of all target lesions.
STABLE DISEASE--Shrinkage less than 30% or increase less than 20%.
PROGRESSIVE DISEASE--20% or greater increase in the sum of diameters from the smallest sum (the nadir) previously recorded.
CreativBio is doing the measuring of ctDNA for Cytodyn, but the Targeted Oncology article was based on an assay developed by Personalis (PSNL). Here's a link to their PR:
https://investors.personalis.com/news-release...asensitive
Looks like cancer testing/detection from a blood biopsy is going to become a Big Business. Great news for patients! I did notice another company--GRAIL--just failed a Phase 3 trial in their cancer test though. So there is still work to do. I'm not sure how CreativBio's filter technology compares with PSNL. But the timing with this innovation in cancer detection dovetails perfectly with what Cytodyn is doing.
"Changes in ctDNA levels measured as early as 3 weeks after treatment initiation were highly predictive of long-term outcomes. A molecular response (ctDNA-mR), defined as a ≥ 30% decrease in ctDNA, strongly correlated with improved progression-free survival (PFS) and overall survival (OS).
In the retrospective cohort, patients who achieved ctDNA-mR (≥ 30% reduction) had significantly better PFS (HR, 2.69) and OS (HR, 2.23) compared with non-mR patients. In the validation cohort, the hazard ratios were 2.14 for PFS and 2.56 for OS.
Failure to achieve mR demonstrated a positive predictive value of 100% for identifying non-responders. Conversely, 100% of patients who achieved a complete or partial response by imaging had a ctDNA decrease at the pre-C2 timepoint."
(The pre-C2 timepoint they mention--which stands for Cycle 2--refers to the blood sample collected right before the administration of the second dose of immunotherapy. That is usually 3 to 4 weeks after the first dose. Quick!
https://www.targetedonc.com/view/ctdna-assay-...id-tumors#
30% seems to be the magic number for responders when measured by imaging or ctDNA count. Since ORR numbers are still going to be important in the mCRC trial, I dug up the standard RECIST guidelines (Response Evaluation Criteria in Solid Tumors, for those, like me, who didn't know what the acronym meant):
PARTIAL RESPONSE--30% or greater decrease in the sum of diameters of target lesions (up to five measurements to account for irregular tumors).
COMPLETE RESPONSE--Disappearance of all target lesions.
STABLE DISEASE--Shrinkage less than 30% or increase less than 20%.
PROGRESSIVE DISEASE--20% or greater increase in the sum of diameters from the smallest sum (the nadir) previously recorded.
CreativBio is doing the measuring of ctDNA for Cytodyn, but the Targeted Oncology article was based on an assay developed by Personalis (PSNL). Here's a link to their PR:
https://investors.personalis.com/news-release...asensitive
Looks like cancer testing/detection from a blood biopsy is going to become a Big Business. Great news for patients! I did notice another company--GRAIL--just failed a Phase 3 trial in their cancer test though. So there is still work to do. I'm not sure how CreativBio's filter technology compares with PSNL. But the timing with this innovation in cancer detection dovetails perfectly with what Cytodyn is doing.
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