Study on GDC0077

Babs, Thank you for starting this thread to document the steps you are taking as you prepare for the trial as well as your experiences once the trial begins. It sounds like you are busy already. I hope the treatments prove to be effective for you and others. It takes a special person to participate in a clinical trial, and I appreciate you and others who are doing it. I look forward to reading your updates. In the meantime, enjoy your trips.

Hugs and prayers, Lynne

Hi Babs,

We are here to cheer you on!! As we have discussed on earlier threads, the PI3K mutations are the most common mutation that crops up as breast cancer become resistant to any of various therapies. But the problem has been to get an inhibitor that works better and with far fewer side effects than a drug like Affinitor. Your trial will test a new PI3K alpha-subunit specific inhibitor, alone or with Ibrance-Femara.

I don't see much info out about this new drug, other than a short report that just came out last month:

A structure-, property-, and phenotype-guided strategy directed at high PI3K-isoform and PIKK-family selectivity, as well as a distinct cellular mechanism of action, culminated in the discovery of GDC-0077. Differences in primary and tertiary structure among PI3K isoforms were leveraged to achieve >300-fold selective inhibition of the PI3Kα isoform over the β, δ, and γ isoforms in biochemical assays. Very high selectivity over PIKK-family proteins such as mTOR, DNA-PK and VPS34 was also achieved through this process. In vitro and in vivo data indicate that GDC-0077 operates by a mechanism that promotes the selective degradation of "hotspot" p110α mutants (H1047R, E545K). Treatment of nude mice bearing PIK3CA-mutant breast tumor xenografts with oral GDC-0077 resulted in tumor regressions at well-tolerated doses. Together, the high degree of isoform selectivity, selective degradation of mutant-p110α, and in vivo PK/efficacy support the clinical evaluation of GDC-0077 as a treatment for patients with locally advanced or metastatic, PIK3CA-mutant cancer.

Basically, this drug is supposed to go in and degrade the mutant PI3K that is driving your cancer cell growth. As with all drugs, the cancer will eventually find a way to mutate some other protein and keep growing, however the stronger the drug, and hopefully the benefit of combining it with other drugs like Ibrance, will beat it back for a very long time. Best of luck and we are all with you!

Cheering you on and sending great hopes for the efficacy and tolerability of this trial for yo

following. cheering.

Z

Ugh! I am sorry you have to go through yet another liver biopsy. Nine more days until the trial starts, right? I am keeping you in my thoughts and prayers.

Hugs, Lynne

hey Babs, I did a GDC trial last summer at MSKCC, in combination with Femara. I was fortunate to have a skin met, which is easier to biopsy twice, under the trial protocol. Unfortunately the dermatologist who did the biopsy created a huge scar directly under my left arm that's very visible now. A martyr for the cause. ;-)

I wish you the very best during the trial. Hope you feel fine and have good results.

Hi Babs, Good luck. I am thinking about you. I can't wait to read about your experience on day 1.

Lynne

Hi Babs - thinking of you and wishing great success on this trial!

Wow, Babs, What a crazy day. You must be exhausted. It is a nice benefit to live close to the hospital. Relaxing at home is so much easier than relaxing in a hospital. The fact that you weren't allowed to drink for so long probably didn't help during the blood draws. A little hydration can work wonders. I hope you are able to sleep better tonight. Thank you so much for posting for us. As you know, we will all benefit from reading about your experience.

Hugs from, Lynne

Go Babs!! Thanks for the detail. And doing the trial. A lot of work.

>Z<

Babs just got to this treasure. I can't believe you have to get another biopsy and leave the next day. WOW! Interesting, so they can only see from the biopsy if something is working? Not scans? We'll keep checking on you. Thanks for this info.