Some interesting things found in the updated corporate presentation.
Slide 6 then look at outlined mUM second from bottom.
Observation: Out of 23 patients treated 14 patients were stage M1a. All 14 patients are still alive. Four of those patients are in metabolic complete response at the time of the publication….29%. Median OS not yet reached.
This is updated since results published back in June 2022…20th Congress of the International Society of Ocular Oncology (ISOO), held June 17-21, 2022 in Leiden, The Netherlands. In this presentation over a year old there are 23 patients reported on. Breaking down all 23 patient responses reported at this conference: of the 58 lesions treated and measured using 2D- EASL: 4 mCR…7%, 28% partial responses, 52% stable disease, and 14% progressive disease. There are rounding up being done in this report which ends up adding to 101%.
It is my understanding that it will be a P1+ combo trial with BMY drugs Yervoy and Opdivo targeting only the stage M1a patient population. P1+ meaning likely rolling trial. Endpoints will be OS…with overall patient CR, ORR, PFS using RECIST while another endpoint will be mCR (metabolic complete response) using PERCIST measuring with PET scanners. mCR will be used as a surrogate endpoint for OS with the logic that mCR more accurately indicates the tumor or lesion is dead over RECIST.
The goal of this trial is to target mUM as a first line treatment since standard of care has median OS of only 13.9 months…. while all 14 M1a in the current PVCT P1 mUM combo study are still alive and median OS has not been reached….and this trial is five years plus running. As you may observe several patients are 3 years plus in OS.
Now contrast this to a recent mUM approved drug:
In this approved P3 trial N was 91. ORR was 36.3% (7.7%CR + 28.6% PR)….longest durability of response was 17.7 months with the median response of 14 months. Disease control rate was 73.6%. No median OS rates reported in the press release…so I had to dig some more. The estimated OS by that company to the FDA was 20.53 months by the end of the trial in May 2023.
Further digging: “ORR is much higher than ipi+nivo (Pelster) and tenbentafusp (Nathan), but OS is much lower (you have to root around to find these data).
Administration is very technically challenging and involved, and the black box warnings are non-trivial.” -Anonymous Consultant
In comparison, the 23 patients PVCT has treated shows CR 7%, ORR of 34% and DCR of 83% using 2D-EASL measuring. Median DCR has not been reported yet.
Now if PVCT moves ahead as planned to target first line combo therapy for just the M1a mUM patients in a P1+ trial… looking at the multi-year 14 M1a patients already treated the OS for those patients are 100%. DCR for these 14 M1a patients has yet to be reported. Median M1a OS has not been reached….5 years plus this trial has been going on. A patient has to die to determine median OS for M1a. None have so far.
Now what will be the early goals of a future mUM M1a P1+ trial? Use mCR as a surrogate for OS. Report mCR at mid trial. This logic becomes more clear when the durability of OS…over years…becomes public for the M1a patients already treated…. especially the 4 mCR patients. I expect MD Anderson to run this upcoming trial as well.
In addition: immunological markers and levels will be tested before treatment starts then PV-10 injected into all lesions, followed by testing the immunological markers and levels at one week after PV-10 injection of all lesions prior to Yervoy and Opdivo administration to determine level of PV-10 as a immunological drug. This type of data collection has never been done before on a previous PV-10 trial.