Such a bummer!!!! An apparent end to the ECHO 301 trial testing epacadostat (an IDO inhibitor) combined with the anti-PD-1 product Keytruda (pembrolizumab) for melanoma

That is really unwelcome news!!!  I had placed a lot of hope on this combo!  And I was not alone!!!

Pembro (Keytruda) and epacadostat - a promising combo for melanoma 

In that post I note:

Epacadostat, an IDO inhibitor, studied in combination with Pembrolizumab (anti-PD-1, also known as Keytruda) since the ECHO-204 trial started in 2015, has now morphed into the ECHO 301 study for melanoma patients.   I've been impressed by the data coming out on the combo for awhile, posting this in March of 2016: Immunology webinar update by Dr. Weber

While the webinar covered many topics, there was this on the combo: 

Epacadostat (an IDO inhibitor) + Pembrolizumab:Preliminary Results

                61 patients were enrolled by September 2, 2015  Safety data on 46 patients (19 melanoma, 7 RCC, 7 NSCLC, 5 transitional cell carcinoma, 4 endometrial adenocarcinoma). Most common all-grade treatment-related AEs were rash (22%), fatigue (17%), nausea (11%), and pruritus (11%).   Grade 3/4 treatment-related AEs occurred in 13% of patients (rash, 7%).   One patient discontinued for a treatment-related AE.  IDO inhibitor did not seem to increase side effects.  Melanoma patients only (n - 18) - 56% ORR.  Melanoma treatment naive patients (n - 16) - 63% ORR.  Weber found these results very promising and comparable to the ipi/nivo combo in regard to response rates but with much milder side effects!!!

Within the same link....I also posted:

Now...we have this:  Weber's report: Pembro plus Epacadostat as frontline melanoma treatment

In the link above, Shannon Connelly's June 29, 2017 OncLive report, notes the following:

   'If mature data from the ongoing phase III trial of pembrolizumab (Keytruda) combined with epacadostat are positive, the combination could become the preferred frontline treatment regimen for patients with melanoma, says Jeffrey Weber, MD, PhD.

The ongoing KEYNOTE-252/ECHO-301 study is exploring the efficacy, safety, and tolerability of the PD-1 inhibitor pembrolizumab with the first-in-class IDO1 inhibitor epacadostat in patients with stage III/IV unresectable or metastatic melanoma (NCT02752074).

Findings of the multi-arm, open-label phase I/II ECHO-204 trial of pembrolizumab/epacadostat in patients with advanced solid tumors presented at the 2017 ASCO Annual Meeting showed the combination demonstrated an objective response rate (ORR) of 63% and a complete response (CR) rate of 5% for patients with treatment-naïve melanoma. Based on the projected 2-year survival data, the combination could represent a new, less toxic frontline standard of care for patients with melanoma, said Weber, a medical oncologist and deputy director of the Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center.

“The 1- and 2-year survivals are projected to be as good as ipilimumab (Yervoy)/nivolumab (Opdivo), which means a 64% 2-year survival rate,” Weber said. “Let's say it's around a 62% 2-year survival rate. Given the very favorable toxicity profile, a lot of doctors will want to use pembrolizumab/epacadostat in the frontline setting.”'

So...as has been proven out in other studies...it may be that naive patients do the best...and they are the only folks in this trial.  But, even so - an ORR of 63% and CR of 5% is just as good as the ipi/nivo combo while epacadostat has far fewer side effects than those produced by ipi.  If these numbers hold...The Wizard Weber may be on to something here!! Thanks, ratties!!  

Sadly, today there is this:  Incyte’s cancer drug fails trial, marking major blow for immunotherapy combination treatment. By Adam Fuerstein 

"Incyte said Friday that its experimental drug epacadostat failed to improve the efficacy of Merck’s checkpoint inhibitor Keytruda when the two drugs were used together to treat patients with newly diagnosed melanoma.

The negative outcome of the Incyte Phase 3 clinical trial, known as ECHO-301, has far-ranging ramifications. It’s a big setback for Incyte and for melanoma patients. But the trial results could also ripple across the fledgling cancer immunotherapy field and the biotech stock sector."

My heart hurts for the ratties who were counting on this!!  While the advent of BRAF/MEK and immunotherapy (ipi, nivo, and pembro) changed the world of melanoma in almost miraculous ways for those of us lucky enough to gain a response to them ~ they leave far too many melanoma patients behind.  Only about half of us are BRAF positive.  The anti-PD-1 products when given alone help only about 40% of us.  The ipi/nivo combo gains a response for about 50% of us, but comes with some difficult side effects for a goodly number.  This experience shows the danger of putting too much credence on studies with such small numbers, like the 19 melanoma patients in the initial trial.  Still, we have to start somewhere.

As my favorite professor (He taught geology...yes, I took geology!  It's a long story!!!) of all time used to say, "We begin again!"

And so we shall.  Thanks ratties.  You continue to lead the way!  - c