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December 5, 2014 at 10:04 am #22267MathewRParticipant
In 2013, there was a Phase I trial combining dabrafenib and ipi. (There was also an arm that included mekinist, but it was suspended due to a disproportionate number of patients experiencing colitis.) As a Phase I trial, the purpose was to test safety and tolerability–but does anyone have a sense for how the patients on this trial are doing? At one point in the not-so-distant past, folks were very optimistic about this combo. Thanks.December 5, 2014 at 11:26 am #65917rick1981Participant Hi Matt,
Not sure about the research but our MD discussed this as a logical step after coming off the BRAF/MEK combo.December 5, 2014 at 12:36 pm #65918Catherine PooleKeymaster
It was my understanding that the IPI combined with Braf inhibitor (zelboraf) caused liver toxicity and the study was halted. Here is the study you refer to, looks like it is still recruiting: http://clinicaltrials.gov/ct2/show/NCT01940809I’ve been unable to locate any data on it that is current.December 5, 2014 at 3:52 pm #65919MathewRParticipant Catherine, I can’t access the link. I know that the trial with Zelboraf and ipi was discontinued due to liver toxicity. I don’t believe that the same liver toxicity issue exists with Tafinlar and ipi.December 5, 2014 at 11:00 pm #65920Catherine PooleKeymaster You are correct, it was zelboraf, I was trying to find that report. The one I listed I will try to cut and paste here although this isn’t what I was trying to find either: Objective responses can be obtained by CTLA-4 inhibition in metastatic melanoma after BRAF inhibitor failure. Schreuer, Max S.; Chevolet, Ines L.; Jansen, Yanina J.; Seremet, Teofila C.; Wilgenhof, Sofie; Liénard, Danielle; del Marmol, Veronique; Neyns, Bart
The aim of this study was to determine the activity of ipilimumab (ipi)-based therapy after treatment failure with a BRAF inhibitor (BRAFi). Sixty-four patients with unresectable stage III or stage IV BRAF V600-mutant melanoma who were treated sequentially with a BRAFi and ipi-based therapy [ipi as monotherapy or ipi in combination with an autologous mRNA electroporated dendritic cell vaccine (TriMixDC-MEL)] were identified. Thirty-three patients had been treated with a BRAFi before ipi-based therapy (BRAFi-first), and 31 patients had been treated with ipi-based therapy first (ipi-first). In patients treated with a BRAFi first (n=33), the best response on sequential ipi-based therapy was three complete responses and six partial responses (best objective response rate of 27%). In patients treated with ipi-based therapy first (n=31), the best response on ipi-based therapy was 0 complete response and four partial responses (best objective response rate of 13%). The response rate did not differ significantly between the two groups (P=0.14). The median overall survival from the start of ipi-based therapy was 10 months (95% confidence interval: 5.7-14.3) in the BRAFi-first group and 12.3 months (95% confidence interval: 7.4-17.2) in the ipi-first group (P=0.34). We report that objective tumor responses to ipi-based immunotherapy can still be obtained after progression has occurred upon treatment with a BRAFi. A part of this observation might be related to the results obtained with a combination of ipi and TriMixDC-MEL.
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