During the investors conference Dr. Aniline mentioned a Nature Cancer article by Scott V. Bratman et-al “Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab”.
https://ce.mayo.edu/sites/default/files/Bratm...ressed.pdf
This paper constitutes good reading and is enlightening (and critical) in the context of the ctDNA clearances and RECIST implications that we are observing in CLOVER and merit further discussion.
In a nutshell:
>=90 reduction/full clearance meant almost always PR or CR , in their study all 12 patients with clearance had objective responses and 100% OS. Clearance often preceded RECIST response, all alive at median 25.4 months; long term responders across all tumor types.
50%-89%: Mostly PR or durable SD, strong clinical benefit group . Many showed tumor shrinkage (−30% or more) or long SD ≥ 6 cycles of Keytruda.
And Dr. Anilne goes on to say: “I think I made a comment that you guys need to get out and talk to your investors pretty soon because this data (CLOVER ctDNA clearance) looks really remarkable.”
Well, it is. Why ?? Obviously the implication is that the ctDNA clearance will result in RECIST data, it did for KEYTRUDA, of course. CLOVER had a 93% average reduction in12 of the patients reported (with clearance >= 89%).
However, the point is that even for 50%-89% clearance there where some patients that showed tumor shrinkage (−30% or more). We have 13 patients out of the total September cohort of 28 in this range with only 3 patients with ctDNA clearance lower than 50% !!
The comparison is obviously not apples to apples (mechanism of action is very different), but if we correlated ctDNA clearances we should be very hopeful about the upcoming data early next year in S.F.
https://ce.mayo.edu/sites/default/files/Bratm...ressed.pdf
This paper constitutes good reading and is enlightening (and critical) in the context of the ctDNA clearances and RECIST implications that we are observing in CLOVER and merit further discussion.
In a nutshell:
>=90 reduction/full clearance meant almost always PR or CR , in their study all 12 patients with clearance had objective responses and 100% OS. Clearance often preceded RECIST response, all alive at median 25.4 months; long term responders across all tumor types.
50%-89%: Mostly PR or durable SD, strong clinical benefit group . Many showed tumor shrinkage (−30% or more) or long SD ≥ 6 cycles of Keytruda.
And Dr. Anilne goes on to say: “I think I made a comment that you guys need to get out and talk to your investors pretty soon because this data (CLOVER ctDNA clearance) looks really remarkable.”
Well, it is. Why ?? Obviously the implication is that the ctDNA clearance will result in RECIST data, it did for KEYTRUDA, of course. CLOVER had a 93% average reduction in12 of the patients reported (with clearance >= 89%).
However, the point is that even for 50%-89% clearance there where some patients that showed tumor shrinkage (−30% or more). We have 13 patients out of the total September cohort of 28 in this range with only 3 patients with ctDNA clearance lower than 50% !!
The comparison is obviously not apples to apples (mechanism of action is very different), but if we correlated ctDNA clearances we should be very hopeful about the upcoming data early next year in S.F.
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