Monday, July 3, 2017

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

While this year's ASCO didn't provide any new amazing drug or therapy promising a cure for melanoma...but rather offered data from the maturation of existing studies and additional supporting data for current accepted therapies...there was one combo that just may offer a possible change/better treatment option in the future.  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!!!

In December of last year, there was this:  The Future for Melanoma Treatment = Combo's! Dr. Weber breaks it down -

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.”' has been proven out in other 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!!  Happy 4th! -c

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