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Immunotherapy drugs for breast cancer

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  • JohnSmith
    JohnSmith Member Posts: 61
    edited September 2016

    For others just discovering the power of Immunotherapy, another option are "CD47 inhibitors".
    There is a thread dedicated to CD47 Immunotherapy called: "CD47 Research at Stanford".

    In a nutshell, CD47 inhibitors (Anti-CD47) have the potential to specifically kill tumors and boost immune response to distant tumors wherever they reside. Furthermore, because CD47 inhibitors are known to PROTECT normal cells against both chemo and radiation therapy, it is anticipated that many of the side effects of metastatic breast cancer treatments will be reduced or eliminated by using this therapy.

    As of August 2016, there are a number "Anti-CD47" immunotherapy Clinical Trials. For solid tumors (which includes breast cancer), these three trials are open and/or ongoing:

    1. Phase I Trial of Hu5F9-G4 (Hematologic Malignancies or Solid Tumors)
    https://clinicaltrials.gov/ct2/show/NCT02216409
    This trial was accepting breast cancer patients, but may no longer be recruiting since they are nearing closure. Phase II trials may start in late 2016.
    Sponsor: Stanford
    Drug: Hu5F9-G4
    Estimated Enrollment: 36
    Study Start Date: August 2014
    Estimated Primary Completion Date: August 2017
    Location: California (Palo Alto - Stanford University)

    2. Phase 1, Dose Finding Study of CC-90002 in Subjects With Advanced Solid and Hematologic Cancers
    https://clinicaltrials.gov/ct2/show/NCT02367196
    This trial accepts breast cancer patients.
    Sponsor: Celgene
    Drug: INBRX-103 (CC-90002)
    Enrollment: 100
    Study Start Date: March 2015
    Estimated Primary Completion Date: December 2017
    Locations: Arizona (Scottsdale Healthcare Research Institute), California (University of California San Francisco: Lead researcher is Dr. Pamela Munster), Texas (South Texas Accelerated Research Therapeutics)

    3. Trial of Intratumoral Injections of TTI-621 in Subjects With Relapsed and Refractory Solid Tumors
    https://clinicaltrials.gov/ct2/show/NCT02890368
    This trial accepts breast cancer patients.
    Sponsor: Trillium Therapeutics
    Drug: TTI-621
    Enrollment: 54
    Study Start Date: October 2016
    Estimated Primary Completion Date: December 2018
    Locations: California (City of Hope National Medical Center), Oregon (Oregon Health & Science University), Pennsylvania (University of Pittsburgh), Washington (University of Washington Seattle Cancer Care Alliance)

  • Longtermsurvivor
    Longtermsurvivor Member Posts: 738
    edited March 2016

    Hi John,

    Another bco member directed me to this topic/thread.

    While I'm not interested in this for myself, I was in a support group with a man who used a PD-1 drug to achieve complete remission of metastatic melanoma with very few unwanted effects. Will there be long term, unwanted effects? Will the cancer find its way around these new drugs, like it has the older chemotherapy agents? Only time will tell. In the meantime, he's having a good time.

    Here's a resource with many patient reports at Smart Patients (free registration required):

    https://www.smartpatients.com/tags

    Scroll down to drugs and targets for specific information.

    They too have great resources for clinical trials.

    Stanford is doing CD47 trials and there's also this lead that you may want to pursue:

    A Phase 1, Dose Finding Study of CC-90002 in Subjects With Advanced Solid and Hematologic Cancers

    more information:

    http://oncologydiscovery.com/2015/11/04/trillium-t...

    Good wishes for your good intentions, Stephanie

  • letmywifelive
    letmywifelive Member Posts: 303
    edited March 2016

    Spoke to Trillium Therapeutics about Metastatic Breast Cancer in context of Trial NCT02663518. Following is the response.

    "Trillium Therapeutics is committed to expediting evaluation of SIRPαFc for patients with cancer. It has just begun and is recruiting patients with advanced lymphoma, and there are no results that have been published.

    We do not know when the phase 1 trial will be complete and we have not reported plans for solid tumor trials.

    We are not yet conducting trials for breast cancer. I propose that you follow our press releases closely where such plans will be announced. Feel free to subscribe:
    http://trilliumtherapeutics.com/investors/email-alerts/default.aspx".

  • Longtermsurvivor
    Longtermsurvivor Member Posts: 738
    edited March 2016

    Any more details on the Phase I trial for advanced solid tumors?

    It may interest some bco members.

    best, Stephanie

  • letmywifelive
    letmywifelive Member Posts: 303
    edited March 2016

    Based on the responses I got from them, they are yet to report plans for solid tumor trial.

  • MusicLover
    MusicLover Member Posts: 777
    edited March 2016

    LMWL, I think that LTS means that we should follow up with Celgene who is doing a phase 1 on solid tumors right now, she included a link. I guess that Trillium is not at this point. Maybe someone will help summarize what is going on in this field at the moment. Hang in there.

  • letmywifelive
    letmywifelive Member Posts: 303
    edited March 2016

    I have an appointment for my wife next Wednesday at UCSF and I plan to get details from them about the Celgene trials.

  • JohnSmith
    JohnSmith Member Posts: 61
    edited March 2016

    In terms of Anti-CD47, all details for breast cancer patients are posted above. Also, please refer to page 1 of the dedicated CD47 thread called: "CD47 Research at Stanford" to review all of the entities and trials.
    I've made a concerted effort to make sure all of the details are updated and available for patients.

    In short, only Stanford and Celgene are exploring Anti-CD47 Immunotherapy for solid tumors (at the moment). The only other entity doing CD47 trials is Trillium, but they are testing Anti-CD47 against hematological malignancies (i.e. blood cancers, lymphoma, etc).
    At some point in the future, Trillium said they would start a trial for solid tumors. It might be years before this happens since they are quite small, have limited resources/money, etc.

    This past January at the Personalized Medicine World Conference 2016 (PMWC 2016), Dr. Irv Weissman was among a handful of session chair speakers that included the new FDA chairman, Robert Califf.
    Dr. Weissman announced in this recent video, here - skip ahead to ~9:30 minute mark, that Stanford University is nearing completion of the Phase 1 trial. He also revealed the creation of a new company called "Forty Seven Inc" that will take Anti-CD47 therapy to Phase II trials, which hopefully will focus on solid tumors, including breast cancer.

    This CD47 approach, while promising, is one of DOZENS of Immunotherapy approaches. As mentioned earlier, there are ~241 different clinical trials for Immunotherapy in breast cancer. That number will continue to grow as the industry recognizes the benefits of Immuno-Oncology.

  • MusicLover
    MusicLover Member Posts: 777
    edited March 2016

    JS, Thank you, that was very helpful.

  • funthing42
    funthing42 Member Posts: 236
    edited March 2016

    Awesome research. Knowledge .I have so much fear . I'm being worn down. I had a 4% chance that this would come back . No one every put any effort into the latest developments. Only because I was a manageable stage 1. No nodes. NO Nodes second time.

    Well things escalated. One month after chemo. It came back locally in the skin.

    Last week my markers went up less than a year after my second round of radiation to get rid of the skin recurrence .

    Now I have 4 nodes. 3 under my arm /axilla. And 1 under pectoral muscle on the left. Originally on the Right.

    Crap. 40 years old. When this all started. Hmmmm.

    I feel like I'm you know screwed. Too exhausted with could have should haves.


  • letmywifelive
    letmywifelive Member Posts: 303
    edited March 2016

    Read about this revolutionary therapy being provided at UCLA for brain tumors. Highly inspiring.

    http://www.stopcancer.org/Main/default/LongTopicDe...


  • letmywifelive
    letmywifelive Member Posts: 303
    edited March 2016

    UCSF is carrying on a new trial by adding α selective PI3K inhibitor to CDK4/6 inhibitor and Letrozole (AI). They are currently accepting Stage IV patients who are naturally menopausal. This is considered superior to current new combo therapy of Ibrance (CDK4/6 inhibitor) and Letrozole (AI).

    This is for ER+ and HER2- patients only.

    http://meetinglibrary.asco.org/content/127461-144


  • JohnSmith
    JohnSmith Member Posts: 61
    edited March 2016

    Awesome LMWL.
    However, none of those drugs in the clinical trial (NCT01872260) are Immunotherapies.

    1. PI3K: LEE011
    PI3K drugs inhibit the PI3K pathway. This is a major pathway used by many types cancers including most breast cancers.
    In Lobular, 50% of tumors have mutations in at least one of the three key genes of the PI3K pathway (PIK3CA, PTEN, and AKT1).
    In Ductal, it's probably just as common, but I don't research IDC.
    There have been numerous trials evaluating PI3K inhibitors. In fact, the "RATHER" consortium in Europe focuses on Lobular and has a Phase I/II clinical trial called POSEIDON which is evaluating PI3K inhibitors.
    Also, this thread, here, discusses some of the challenges with PI3K.

    2. CDK4/6: BYL719
    CDK4/6 drugs target the rapid division of tumor cells by inhibiting the activity of the enzymes CDK4 and CDK6.
    Ibrance is a CDK4/6 inhibitor proven in clinical trials to improve progression free survival (PFS) for metastatic patients.
    In fact, Ibrance is now being tested in early stage patients in the large Phase III trail called "PALLAS".

    3. AI's: Letrozole (Femara)
    AI's stop the production of estrogen.

    This is an interesting combination. In theory, it should be very effective, but at what cost, in terms of Quality of Life (QoL)?
    Each drug has their own side effect profile.
    How are they combining them to avoid excessive toxicity? That would be the first question I'd ask.

    Again, these drugs fall outside of the scope of Immunotherapies.
    I encourage you to start a new thread discussing this trial.

    I hope the second opinions for your wife are productive. Feel free to call my mobile or send me a PM.

  • letmywifelive
    letmywifelive Member Posts: 303
    edited March 2016

    JS,

    Thanks for the very helpful details. Can you give some examples of immunotherapy for MBC and if some of those are available as FDA approved therapies ?

  • Longtermsurvivor
    Longtermsurvivor Member Posts: 738
    edited March 2016

    You may be interested in a recent NYT article, comments from leading oncologists on precision medicine and personalized treatments in advanced breast cancer:

    A couple of decades ago, breast cancer seemed to be on the leading edge of personalized treatments. The first precision medicine drug, Herceptin, was developed and approved for a subset of breast cancer patients in the 1990s.

    Yet now, as powerful new precision medicine drugs elicit striking responses in patients with other cancers — lung, colon, melanoma, blood, gastric — metastatic breast cancer patients have been left out.

    "It's like standing outside a candy store on Sunday when the store is closed, looking in the window," said Dr. Gabriel N. Hortobagyi, a director of breast cancer research at MD Anderson Cancer Center in Houston.

    There is no obvious reason breast cancer in particular should be so resistant to new therapies. But the situation is one of the starkest examples of the frustrating reality of precision medicine today. While labs can test for hundreds of genes that have been linked to cancer, and while the tests may find likely culprits, there all too often is nothing that can be done.

    "As a concept, it is beautiful," Dr. Hortobagyi said. "In practice, we face a number of obstacles. Most breast cancers have not just one but four, six, 10, sometimes 15 or 20 mutations. So which is the driver mutation and which are the passengers? That's a tall order."

    Even if investigators have a good idea of which mutation to go after, there may be no drug that blocks it. Or there may be a drug being tested in a clinical trial but the woman is not eligible because, for example, she has had two rounds of chemotherapy and the trial's rules say she can have no more than one.

    Or there is a drug that was approved for a different cancer, but it costs more than $100,000 a year and her insurer will not pay. Sometimes, a drug that works against a mutation in one type of cancer also works against that same mutation in another cancer, but sometimes it does not.

    Dr. Norman Sharpless, the director of the Lineberger Comprehensive Cancer Center at North Carolina, estimates that perhaps one in 1,000 women with advanced breast cancer will benefit from using the approved and experimental drugs available today.

    "There are a few who benefit tremendously, but when patients come in expecting a cure, most are disappointed," he said.

    http://www.nytimes.com/2016/03/12/health/breast-ca...

  • letmywifelive
    letmywifelive Member Posts: 303
    edited March 2016

    Longtermsurvivor

    The above does not sound like a very encouraging summary of the current situation.

  • Longtermsurvivor
    Longtermsurvivor Member Posts: 738
    edited March 2016

    Hi LMWL,

    Well, the doctors are in the trenches (if you believe cancer is a war), while the drug companies producing the news releases are rallying the troops with battle cries. We cancer patients are the foot soldiers and cannon fodder and treatments are the weapons and ammunition.

    Personally, I've never done the war and battle imagery thing, but I recognize the language and thinking.

    If you have time, you might read The Emperor of All Maladies: A Biography of Cancer by Siddhartha Mukherje to better understand the territory and strategies.

    Or you can watch it online here:

    http://www.pbs.org/show/story-cancer-emperor-all-maladies/

    And don't forget to come to Forum 8 where there are many with mets and Stage IV cancer. It's subdivided by topics like treatment approaches and mets site(s). Keep looking for viable treatments, but don't forget to seize the day and enjoy life. None of us know how long we have and our good connections sustain us.

    Best healing wishes, Stephanie in California

  • letmywifelive
    letmywifelive Member Posts: 303
    edited March 2016

    Saw the first three episodes of www.pbs.org/show/story-cancer-...

    Feeling depressed about how far we are from cure or even prolonged lifespan for people with metastatic disease.

  • JohnSmith
    JohnSmith Member Posts: 61
    edited September 2016

    LMWL
    Unfortunately, Immunotherapies for ER+ disease are still in trials and need to be validated before FDA approval.

    However, according to the Cancer Research Institute (CRI), there are 241 clinical trials for Immunotherapy.
    CRI offers a search tool on their website which can generate a report (excel spreadsheet) of these IO trials. Sadly, this report doesn't stratify the trials by biomarker (ER, HER2) or Stage, making it difficult to identify good matches. It also lacks location data. If this list was sorted by these parameters, it would quickly reveal the options for your wife and anyone else reading this. It's extremely time consuming to manually add the data to the spreadsheet, but it is a project that I'm considering doing.
    Other methods to identify IO trials for MBC include BreastCancerTrials.org
    The site offers great functionality to add your diagnosis data, but the results aren't very useful since it doesn't parse the Immunotherapy trials.
    The BCO Metastatic trial search tool seems to suffer the same problem and does not parse the IO trials either.

    To answer your earlier question,
    Currently, HER2+ and TNBC seem to be the beneficiaries of breast cancer Immunotherapies.
    For HER2+, they have trastuzumab (Herceptin) and pertuzumab (Perjeta) and, in the case of advanced cancer, lapatinib (Tykerb) or ado-trastuzumab emtansine (Kadcyla).
    Perjeta was approved by the FDA in 2012 for first-line treatment of metastatic HER2+ in combination with Herceptin and the chemo docetaxel (Taxotere).
    Kadcyla is a HER2-targeted antibody with chemo attached by a linker, and is designed to deliver chemo directly to the tumor via HER2.
    Kadcyla was approved by the FDA in 2013 for patients with HER2+, metastatic breast cancer who have previously received Herceptin and taxane chemo separately or together.

    TNBC is seen as more "mutant", thus the potential for the immune system to recognize the tumor mutational load is greater.

  • MaggieCat
    MaggieCat Member Posts: 315
    edited March 2016

    Kadcyla is available to early stage Her2+ BC in the ATEMPT clinical trial..


  • letmywifelive
    letmywifelive Member Posts: 303
    edited March 2016

    Just learnt about Sagely Health (sagelyhealth.com). A commercial service, but they are seeking out novel treatments for patients based on detailed knowledge of the tumor. I am going to contact them to help navigate me through the many options available today. Recommended by Dr. Brian Druker (remember Gleevec ?).

  • Longtermsurvivor
    Longtermsurvivor Member Posts: 738
    edited March 2016

    Hi LMWL,

    You may want to check out Mark Renneker and Dwight McKee too.

    http://tns.commonweal.org/tag/cancer/

    And don't miss Keith Block's book, Life Over Cancer, and his practice in Chicago.

    May you find the solutions you seek, Stephanie

  • letmywifelive
    letmywifelive Member Posts: 303
    edited March 2016

    Thanks. Longtermsurvivor. I will definitely take a look.

  • letmywifelive
    letmywifelive Member Posts: 303
    edited March 2016

    Heard from UCSF today that they are moving ahead with the CD47 trial and occasionally providing openings for new patients who have failed conventional therapies. Still in Phase 1 but I am gathering more info on the success rate of the Phase 1 trial and hopefully Phase 2 dates.

  • letmywifelive
    letmywifelive Member Posts: 303
    edited March 2016

    I was listening to this recording of a session of LBBC conference in (probably 2015) and heard Dr. Minetta C Liu MD of Mayo Clinic cover immunotherapy topic. If you skip ahead to 1:00:00 hr into the recording, she is talking about a vaccine therapy that they have gone through trials for multiple myeloma. It sounded very promising and Dr. Liu said that she is leading the group to introduce it for breast cancer.

    Here is an interview of a woman who was traded in a few days with this therapy after 10 years of suffering with multiple myeloma. It sounded amazing.

    http://www.usatoday.com/story/news/nation-now/2014...

    More info : http://newsnetwork.mayoclinic.org/discussion/mayo-...

    Anyone knows about the trials of Dr. Liu in context of Breast Cancer ?


  • heidihill
    heidihill Member Posts: 1,856
    edited March 2016

    LMWL, thanks for the video, which includes info on other promising treatments.

  • letmywifelive
    letmywifelive Member Posts: 303
    edited March 2016

    My pleasure Heidihill. If anyone has heard more about the vaccine therapy in context of breast cancer please share.

  • heidihill
    heidihill Member Posts: 1,856
    edited March 2016

    This is not about a specific drug but a new approach to immunotherapy.

    http://www.cancerresearchuk.org/about-us/cancer-ne...


  • JohnSmith
    JohnSmith Member Posts: 61
    edited March 2016

    Todays news in the Washington Post:
    "Bloomberg, others give Johns Hopkins $125 million for Immunotherapy cancer research that helped Jimmy Carter"

    Some excerpts:
    "And while there's no magic bullet to defeat the disease, the therapy seems to have enormous potential. This really may have the possibility for a unique eureka moment."

    "The next 10 years will eclipse everything that has happened over the previous 50 years, and maybe longer."

    "The institute would tackle some of the most pressing issues surrounding immune therapy:
    - Why do only 20 to 30 percent of patients respond to the approach?
    - How can genomic sequencing be used to improve the response?
    - Why do some people with certain DNA defects respond better to treatment?"

  • funthing42
    funthing42 Member Posts: 236
    edited March 2016

    Hi thanks for info.

    I currently have been begging for the out of box approach. Ca x 4.

    2009 lump rads

    -2013- back again. B/l mastectomy /chemo.

    Skin locally a month after chemo.

    Back again Almost a year in April since sec RADs now in my nodes on the opposite side in my axilla. I never had cancer on this side.

    I keep thinking I have reccurrence when my Immune system takes a hit. I don't know .