Maxim Report for April answered the question that Oncosec IR did not:
Phase 2b Study in Melanoma. The PISCES Study (Anti-PD-1 IL-12 Stage III/IV
Combination Electroporation Study) is an open-label study in patients with stage III/
IV metastatic melanoma evaluating Immunopulse IL-12 + Keytruda or Opdivo. The
study will enroll 48 patients that have progressed or are progressing within 24 weeks
of receiving available checkpoint therapies. The primary endpoint of the study will
be overall response rate (ORR) after 24 weeks, with secondary endpoints of best
overall response rate (BORR), duration of response (DOR), progression free survival
(PFS) and overall survival (OS). The study should start in 2Q17. Oncosec is targeting
completion of enrollment by YE17 and top-line data in early 2019. If positive Oncosec
could file for approval in 2019.
Targeting the non-responders. Over 60% of cancer patients are not responsive
to checkpoint therapy (Keytruda, Opdivo),Oncsec has demonstrated that DNAbased
IL-12 turns cold tumors (non-immunogenic) hot (immunogenic) to drive tumor
targeting T cells into tumors. This provides the rationale for combination therapy with
a checkpoint (PD-1/PD-L1). In addition, the company recently published a study, led
by Dr. Adil Daud, demonstrating that a novel biomarker assay may predict likely nonresponders
from responders by measuring the amount of T cells in the tumors that
are "high expressors" of both PD1 and CTLA-4 (Dr. Daud also developed an assay
for monitoring PD-L1 expression). The threshold for a responder is ~30% of T cells
expressing high levels of PD-1/CTLA-4; non-responders are defined as having 22%
or less. The ongoing phase II study in melanoma used this assay to enroll 22 patients
(25% or less expression), including six patients that were exposed to up to 30 cycles
of either Keytruda, Opdivo, Yervoy, or combinations of them. Of the responders, five
had TIL high expressers less than 20%, and two had ~21%. The ORR response rate
in the study was 43% (9/21), including patients in the checkpoint failure population.
What is important to note, in addition to the ORR of 43%, is that converting checkpoint
failures to CR and PR is significant. Patients that fail checkpoints are not retreated,
there is no point, thus they are definitive "non-responders."
Maxim has pointed out that the subset of patients who had previous checkpoint therapy in recent data release were in fact checkpoint failures. Good to know that there was absolutely a response in this subset of patients and not sure why Oncosec did not answer e-mails to clarify this data.
