Lilly's CDK4/6 Inhibitor "Abemaciclib" - Breakthrough Status

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Bestbird
Bestbird Member Posts: 2,818
edited May 2016 in Stage IV/Metastatic Breast Cancer ONLY

This is indeed encouraging news, as Abemaciclib appears to be one of the most exciting and effective mbc drugs being studied for hormone receptor positive mbc!

Below is a writeup about it from my MBC Guide (those wishing a free copy of the Guide are welcome to visit: https://community.breastcancer.org/forum/8/topic/8...

LY2835219 (Abemaciclib or Bemaciclib): In October 2015, this oral drug was granted "Breakthrough Therapy Designation" by the FDA, which is a form of Fast Track Designation intended to facilitate the development and review of new drugs intended to treat serious conditions. LY2835219 may have strong single-agent activity in this MBC, meaning that it may potentially be used alone instead of in combination with other drugs (although it may also work in combination with other drugs), and as of January 2015 it is in Clinical Trials.With any luck, it may be available in 2017.

One study included 47 patients with MBC who received a median of seven prior therapies. The majority had two or more metastatic sites and 74% had visceral (internal organ) metastases. Among Hormone Receptor positive patients, 9 (25%) had confirmed partial responses and 20 (56%) had stable disease, including 2 with unconfirmed partial responses.Thee clinical benefit rate was 61%, and disease control rate was 81%.

Even though this drug is highly effective when given alone, it is also being studied in combination with endocrine therapy. A Phase Ib trial of 73 patients evaluated the drug with a variety of endocrine agents and reported an impressive overall disease control rate of 67% among 36 patients treated with LY2835219 and a nonsteroidal AI such as Letrozole or Arimidex.When the drug was paired with Tamoxifen, the disease control rate was and 75% among 16 patients.From: http://2013researchtopractice.cmail2.com/t/ViewEma...

The most common side effects of LY2835219 were diarrhea, fatigue, nausea, vomiting, leukopenia (low white blood cell count), and neutropenia ( an abnormally low count of neutrophils, a type of white blood cell that helps fight off infections).Side effects were tolerable, and no patient discontinued study due to drug-related toxicity. From:http://www.ascopost.com/issues/may-1,-2014/ly2835219-shows-strong-single-agent-activity-in-preliminary-study-in-metastatic-breast-cancer.aspx

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  • blainejennifer
    blainejennifer Member Posts: 1,848
    edited October 2015

    BB,

    How is this different from Ibrance? I'd look, but I have to take a Necessary Nap.

    Many thanks,

    Jennifer

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  • sueopp
    sueopp Member Posts: 1,541
    edited October 2015

    Oh BB - I(we) are so grateful to you for constantly keeping your finger on the science side and for continuing to share with all of us. What you do is so necessary and so important. Thank you very much. Fondly, SUE

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  • Lynnwood1960
    Lynnwood1960 Member Posts: 1,284
    edited October 2015

    Thank you Bestbird! You are a wealth of useful information and really keep on top of things! I have learned so much from your guide also!

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  • Xavo
    Xavo Member Posts: 364
    edited October 2015

    BB, couldn't agree more with all the comments above. So much appeciate your researches and sharing them with us! Thanks!

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  • stagefree
    stagefree Member Posts: 2,780
    edited October 2015

    quite encouraging indeed! Spirits up to survive to catch the cure girls!!!

    You rock my dear, thank you :))

    Ebru

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  • nancyh
    nancyh Member Posts: 2,644
    edited October 2015

    Bestbird - you are such an amazing resource for us, thank you so much.

    It is encouraging to see progress on this drug, I know my doctor is really excited about these types of drugs in general. So, if they expect general availability in 2017, I am hopeful it'll be available sooner on clinical trial and/or via compassionate use.

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  • Bestbird
    Bestbird Member Posts: 2,818
    edited October 2015

    It's wonderful to be able to share encouraging news! The news about Abemaciclib's Breakthrough Designation is highly encouraging!

    Jennifer asked an excellent question about how Abemacicilib compares with IBRANCE. Although both are in the same class of drugs (CDK4/6 inhibitors) it appears as though there are two key differences:

    1) Abemaciclib seems to be effective for heavily pre-treated mbc patients whose prior therapy has failed
    2) Abemaciclib appears to be highly effective in and of itself without needing to be administered with another drug (although clinical trials both with and without a companion drug are underway). IBRANCE is currently administered with Letrozole (or in some cases, Faslodex).

    Another exciting attribute about Abemaciclib is that it can cross the blood-brain barrier, making it a potentially attractive treatment option for brain metastasis and primary brain tumors. From: http://www.onclive.com/publications/contemporary-oncology/2014/november-2014/targeting-cell-cycle-progression-cdk46-inhibition-in-breast-cancer/3#sthash.wCkkuV7J.dpuf Although both IBRANCE and Abemacicilib appear to cross the blood brain barrier, in a mouse study comparing both drugs, abemaciclib brain levels were reached more efficiently at presumably lower doses than palbociclib and are potentially on target for a longer period of time. From: http://www.ncbi.nlm.nih.gov/pubmed/26149830

    As an aside, there's another CDK4/6 inhibitor called LEE011 (Ribociclib) that is also being tested in clinical trials, but doesn't seem to be creating nearly the "buzz" that Abemaciclib is receiving.

    My personal perspective about Abemaciclib is that it may be the most efficacious drug for hormone positive postmenopausal mbc to be developed within the last four years.


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  • GatorGal
    GatorGal Member Posts: 2,550
    edited October 2015

    I want this! LOL!!


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  • Bestbird
    Bestbird Member Posts: 2,818
    edited October 2015

    GatorGal, hopefully one day soon it'll be yours for the asking!

    A quick search on clinicaltrials.gov revealed a handful of recruiting Abemaciclib clinical trials in case anyone may be interested. And although there's a lot of attention being given to this drug, there may be other drugs of interest in the pipeline. Therefore, every so often it may be helpful to run a clinical trials search, either on one's own or by calling 1.800.4.CANCER where a trained representative will conduct a customized search free of charge.

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  • DivineMrsM
    DivineMrsM Member Posts: 9,620
    edited October 2015

    The news is very encouraging

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  • leggo
    leggo Member Posts: 3,293
    edited October 2015

    This is my take on the difference between Ibrance and the other "ciclib's". Same drug, Pfizer got there first with the most $ to throw at its development. They called it Ibrance. Each pharma company then pays for a different clinical trial....used alone, with another drug, with a different drug...anything just different enough to be able to change the name. Or they change a little something in the delivery system just enough to get passed the patent. That way the same drug can be touted as "new", when it's actually the same manufactured by a different pharma company developed under different clinical trials. No different than simple acetominophen that has like 6 different names by 6 different pharma companies because the trials were set up differently or changed the fillers or manufacturing process or something. No company wants to be left out of getting their piece of the giant drug pie. I really hope I'm wrong, but I don't see cancer drugs being any different than any other drug. Changing and paying for a different trial or changing the delivery system is the only way they can "assign" a new name to the "active ingredients" so to speak, as far as I know. I think it's super shady.

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  • Bestbird
    Bestbird Member Posts: 2,818
    edited October 2015

    As per the company, its drug will work better than its rivals as it can be used as a monotherapy with no dosing instructions and direct impact on the brain.

    Time will tell!


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  • leggo
    leggo Member Posts: 3,293
    edited October 2015

    Yes...and I think that's where the big problem lies.....time. Playing stupid pharmaceutical games of "pick me", which wastes everybody's precious time. Something some of us have very little of.

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  • Priscilla0929
    Priscilla0929 Member Posts: 90
    edited October 2015

    Great news!! Thank you so much for sharing!!

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  • GatorGal
    GatorGal Member Posts: 2,550
    edited October 2015

    Bestbird, my oncologist is referring me to Hopkins so I can talk to someone about clinical trials I may be eligible for. Of course I have been waiting 3 days for them to call me, but onc says it is a slow process! I am feeling hopeful!!

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  • Bestbird
    Bestbird Member Posts: 2,818
    edited October 2015

    GatorGal, don't let up! The squeaky wheel usually gets the most results. You may want to prepare your list by double checking with the nIH reps at 1.800.4.CANCER; they will run a complimentary clinical trials search for you based upon your personal history, treatment, and preferences. With that in hand, you'll be fully prepared to take the next step!

    And sometimes it helps for another person to call on your behalf and ask for the Supervisor In Charge! :)

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  • RonnieKay
    RonnieKay Member Posts: 2,067
    edited October 2015

    Thanks for more promising news, Bestbird. 

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  • GatorGal
    GatorGal Member Posts: 2,550
    edited October 2015

    Bestbird,

    Oh, I am going to squeak! LOL! Have already called my onc back. Have been looking at trials for a while. Even have my scientist husband looking for me. Guess all it took was one really crappy pet scan to get me motivated!! Thanks for all you do!!

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  • dlb823
    dlb823 Member Posts: 9,430
    edited October 2015

    Very happy to see this! Thanks for such complete info', Bestbird!

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  • mdillard04
    mdillard04 Member Posts: 100
    edited October 2015

    This is exciting and encouraging!!! Thanks for sharing BestBird!!

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  • Longtermsurvivor
    Longtermsurvivor Member Posts: 1,438
    edited May 2016

    ASCO abstract

    MONARCH1: Results from a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as monotherapy, in patients with HR+/HER2- breast cancer, after chemotherapy for advanced disease.

    Sub-category:
    ER+

    Category:
    Breast Cancer—HER2/ER

    Meeting:
    2016 ASCO Annual Meeting

    Abstract No:
    510

    Citation:
    J Clin Oncol 34, 2016 (suppl; abstr 510)

    Author(s): Maura N. Dickler, Sara M. Tolaney, Hope S. Rugo, Javier Cortes, Véronique Diéras, Debra A. Patt, Hans Wildiers, Martin Frenzel, Andrew Koustenis, Jose Baselga; Memorial Sloan Kettering Cancer Center, New York, NY; Dana-Farber Cancer Institute, Boston, MA; University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; Vall d'Hebron Institute of Oncology, Barcelona, Spain; Institut Curie, Paris, France; Texas Oncology, Austin, TX; University Hospitals Leuven and KU Leuven, Leuven, Belgium; Eli Lilly and Company, Indianapolis, IN

    Abstract Disclosures

    Abstract:

    Background: Abemaciclib is an oral, selective inhibitor of CDK4 and CDK6 dosed on a continuous schedule. In a phase 1 trial, abemaciclib demonstrated single-agent activity in refractory HR+ metastatic breast cancer (MBC) with some tumor responses occurring after 8 or more mos of therapy.

    Methods: MONARCH 1 is a phase 2 single-arm study designed to evaluate safety and efficacy of abemaciclib monotherapy in women with HR+/HER2- MBC whose disease progressed on or after endocrine therapy and chemotherapy. Eligible pts had measurable disease, ECOG PS of 0/1, no CNS metastases, and received at least 1 but no more than 2 lines of chemotherapy in the metastatic setting. Abemaciclib (200 mg) is administered orally on a continuous schedule every 12 hours until disease progression. A sample size of approximately 128 pts was planned to evaluate the primary objective of investigator-assessed objective response rate (ORR) using RECIST v1.1, with interim and final analyses at 8 and 12 mos after the last pt started treatment, respectively.

    Results: A total of 132 pts have been treated with abemaciclib monotherapy. Pts had a median of 3 lines of prior therapy for advanced disease, including a median of 2 lines of chemotherapy for advanced disease. Median age was 58 (36-89), 44.7% of pts had PS 1, 90.2% had visceral disease, and 85.6% had ≥ 2 metastatic sites. At the 8 mo interim, 35.6% of pts had received ≥ 8 cycles of therapy; the confirmed ORR (per RECIST v1.1) was 17.4%, the clinical benefit rate (CR + PR + SD ≥ 6 mos) was 42.4%, and median PFS was 5.7 mos. Of the 22 pts who remained on treatment at the 8 mo interim, 13 had responded and 9 had SD. The 5 most common TEAEs were diarrhea, fatigue, nausea, decreased appetite, abdominal pain; discontinuations due to AEs were infrequent (6.8%).

    Conclusions:Abemaciclib induces objective tumor responses as a monotherapy in pts with refractory HR+ HER2- MBC following multiple prior therapies. Treatment was well tolerated, allowing prolonged exposure to therapy. Updated efficacy and tolerability data will be provided at the time of presentation. Clinical trial information: NCT02102490

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