So, one of the MRF peeps put up a bit of an ad for this treatment...not entirely sure why, as that is not usually their role. Perhaps they were just letting folks looking for a treatment option after failing anti-PD-1 know this trial was enrolling. But, with so little intel out about this study and so many other options available - it piqued my interest. It was quickly apparent that it is hard to find much info on it other than the super slick "presentations" made by the company who makes it, Idera, and the company who wants you to join their trial, MD Anderson, like these:
A Phase 1/2 trial of intratumoral (i.t.) IMO-2125 (IMO) in combination with checkpoint inhibitors (CPI) in PD-(L)1-refractory melanoma - out of MD Anderson
Idera Press Release for investors
But, when my intrepid medical researcher, partner in crime and all things got on the case, he found this: Melanoma News Today - report from April 2017
It reads as follows:
Combining IMO-2125 and Yervoy Shows Promise in Certain Metastatic Melanoma Patients By: Daniela Semedo, Melanoma News Today, April 2017.
Combining {Idera's] intratumoral IMO-2125 treatment with Yervoy (ipilimumab) may be a promising treatment approach for patients with metastatic melanoma who are refractory to anti-PD-1 therapies, according to preliminary data from a Phase 1/2 clinical trial.
“We
are very pleased with the progress to date in the Phase 1 dose
escalation trial of IMO-2125 in combination with ipilimumab, and with
the outcomes observed,” Joanna Horobin, Idera’s chief medical
officer, said in a press release. (Possibly the one I noted above.)
“IMO-2125
in combination with ipilimumab demonstrated preliminary evidence of
meaningful clinical activity in this anti-PD-1 refractory metastatic
melanoma patient population which represents a high unmet medical
need,” she said.
“All
dose levels have been well tolerated and did not exacerbate the
safety issues commonly observed with ipilimumab,” Horobin said.
“Furthermore, data from multiple parameters of immune markers from
tumor biopsies have been very informative in establishing
proof-of-mechanism and supporting the dose selection for the Phase 2
portion of the trial.”
IMO-2125,
a toll-like receptor (TLR) agonist, is designed to activate cells
from the innate immune system and induce the production of interferon
— a potent activator of the immune system. Together, this is
thought to lead to the infiltration of tumor-killing T-cells.
Because
tumors have developed a method to impair T-cells from
recognizing and attacking them, Idera believes that the drug could
work in synergy with known and approved immune checkpoint inhibitors.
The
open-label Phase 1/2 study (NCT02644967)
was designed to assess the safety and preliminary effectiveness
of intratumoral IMO-2125 in combination with the CTLA-4
inhibitor Yervoy or the PD-1 inhibitor Keytruda (pembrolizumab) in
patients with metastatic melanoma who progressed after receiving
anti-PD-1 therapies. The
study was set to be conducted in two parts: a dose-escalation portion
(Phase 1) to evaluate safety and tolerability of multiple dose
levels, and a Phase 2 expansion portion to assess efficacy.
While
the Phase 1 dose escalation of IMO-2125 in combination with
Keytruda is ongoing, the company has now announced that the
Phase 1 part assessing IMO-2125 plus Yervoy has met the pre-specified
futility assessment, meaning that the combination reached the
established efficacy cut-off.
The
company announced that all dose levels of IMO-2125 were well
tolerated, and that the 8 mg dose level was established as the
recommended Phase 2 dose.
Nine
participants out of an expected 21 have enrolled in the Phase 2
portion of the trial assessing the objective response rate of
IMO-2125 in combination with Yervoy. Data will be compared with
historical controls treated with Yervoy alone.
Houston’s
MD Anderson Cancer Center will continue to lead the study and
will be joined by other clinical sites. Idera expects to have overall
response rate (ORR) data early next year.
“I
am very encouraged by the tremendous progress that has been made to
date to advance us to this important stage in IMO-2125’s
development cycle,” said Vincent Milano, Idera’s CEO. “There is
a very clear unmet medical need for those patients for whom current
checkpoint inhibitor therapies are not providing adequate solutions.
“We
are incredibly focused on advancing this program as rapidly as
possible for these patients, and we are also looking forward to
exploring areas outside of melanoma in which intratumoral IMO-2125
may also serve an important role through its unique mechanism of
action within the tumor microenvironment,” he said.
Idera
also said it has started meeting with regulatory agencies about the
best path to follow to register the combined treatment of IMO-2125
and Yervoy in patients with PD-1 refractory metastatic melanoma.
In
addition, the company said the Phase 1 clinical trial evaluating the
combined treatment of intratumoral IMO-2125 and Keytruda in PD-1
patients with refractory melanoma is enrolling as planned. Moreover,
a Phase 1 clinical trial evaluating intratumoral IMO-2125 alone
(NCT03052205)
in multiple tumor types should be enrolling the first patient in
coming months.
Hmmm..... Well, it is certainly a fact that we have folks who fail to gain effective control of their melanoma with anti-PD-1 and it's 40% response rate, leaving them in desperate need of an effective therapy! It is also true that I encourage and fully support looking at any and all possible treatments to help them. Yet, I remain a little puzzled here. This statement sounds strong, but is substantially lacking in, hmmm....what's the word?????? "...data from multiple parameters of immune markers from tumor biopsies have been very informative in establishing proof-of-mechanism and supporting the dose selection for the Phase 2 portion of the trial.” Oh! I know what it is....DATA!!!!!!!!!!!!!!! This report tells us NOTHING about how the folks in the phase 1 trial are doing!!!An interesting aside: The name TLR, toll-like receptor, came from the appearance the fruit fly larvae developed when used as subjects by researchers to isolate the molecule's function. The larvae in whom the receptor was changed, looked very peculiar, or "droll", according to the German researchers who won a Nobel prize in medicine for this work. And the German word for "droll" (i.e. funny) is "toll"! The more you know....
While I hope IMO-2125 will absolutely be the cure for ever so many cancers, including melanoma, we need to remember that current intratumoral/intralesional therapies that are being combined with immunotherapy daily, to good effect, are available for melanoma patients in need and come WITH data supporting their efficacy! Here's a post reviewing a wide variety of them and the DATA required for them to sally forth:
ASCO 2017: All things intralesional/intratumoral
If TLR agonists become the next great thing....will we all be cured of our melanoma AND have a great sense of humor...or just look a little funny????? Hang tough ratties! The road is long with lots of tolls! And I mean LOTS!!! - c
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