Mets Day 1034 I’m becoming a member of the nivolumab trial

Mets Day 1034 I'm becoming a member of the nivolumab trial

Image source: http://images-thumbs.thefullwiki.org/T/r/a/Tramadol.png

For the past two weeks I have been doing an entire lot of follow-up research on the most efficient clinical trial for me. On Friday, January 30, I met with Dr. Alex Spira at Inova Fairfax. I had previously spoken with his clinical trial nurse, which evolved into a considerable sort of email exchanges. Eventually she realized that the technical and distinctive nature of my questions put me outside the area of most patients, and she forwarded my emails to Dr. Spira for direct reaction. He told me that the MPDL-3280a trial he was running was closed to patients like me who had previous platinum-primarily founded chemotherapy. He nonetheless provided to satisfy with me and evaluate other clinical trial probabilities. When we met, he reviewed my clinical trial probabilities, and recommended that I pursue the nivolumab trial at Hopkins. He said that a PD-1 or PD-L1 drug was most likely the most promising option at this aspect. He additionally provided to maintain following me and be handy if I had additional questions, which I appreciated.
On Monday, February 2, I came all through a up to this point article in Lancet Oncology said that MPDL3280a worked most efficient in patients with PD-L1-positive tumor-infiltrating immune cells. I additionally did a piece analysis on Foundation Medicine, and their cancer genome testing program. I sent emails to Drs. Apolo and Aragon-Ching, asking no matter if my tumor tested had been tested for that characteristic, and if that could be so, no matter if it is going to influence the trial I must join. Dr. Apolo responded that, when NIH did the sequencing of my cancer, they didn't test no matter if my immune cells have been PD-L1-positive. In a later conversation, she explained that there was an entire lot of debate in the cancer research community over how to measure for PD-L1-positive qualities: was it 1% of all cells, or 5% of all cells, or more? In addition, she said that researchers have been learning that PD-L1 expression was not an immutable static trait, but may possibly vary over time, and was not permanently understood. She urged me to go forward with a PD-1 or PD-L1 trial without reference to no matter if my tumor had been tested for that characteristic, because it was one of the trials that showed brilliant promise.

(What is the difference among PD-1 and PD-L1? "PD" stands for Programmed Death. As I know it, PD-1 is an inhibitory T-cell co-receptor – a type of protein – that negatively regulates T cell responses. PD-L1 is a ligand of the PD-1 protein that could be expressed on the tumor. The theory is that interactions among PD-1 and the PD-L1 ligand can lead to antitumor immune suppression. The PD immunotherapy drugs in improvement are designed to interact PD-1 on effector T cells, allowing T cells to fight cancer. Scientists are nonetheless making an attempt to determine which kind of tumors respond most efficient to PD drugs, as nicely as knowing the correct dosages without causing unacceptable facet effortlessly on the patient. That's what these trials are for.)

PD-1, an inhibitory T-cell co-receptor, or PD-L1, a ligand expressed on the tumor. It is thought that interactions among PD-1 and the ligands PD-L1 or PD-L2 can lead to antitumor immune suppression; the compounds in improvement are designed to interrupt those interactions, allowing T cells to fight cancer. – See more at: http://www.onclive.com/convention-coverage/nyl-2013/PD-1-and-PD-L1-Inhibitors-Expected-to-Change-the-Landscape-of-Lung-Cancer-Treatment#sthash.nfZRBoJ5.dpuf

PD-1, an inhibitory T-cell co-receptor, or PD-L1, a ligand expressed on the tumor. It is thought that interactions among PD-1 and the ligands PD-L1 or PD-L2 can lead to antitumor immune suppression; the compounds in improvement are designed to interrupt those interactions, allowing T cells to fight cancer. – See more at: http://www.onclive.com/convention-coverage/nyl-2013/PD-1-and-PD-L1-Inhibitors-Expected-to-Change-the-Landscape-of-Lung-Cancer-Treatment#sthash.nfZRBoJ5.dpu
PD-1, an inhibitory T-cell co-receptor, or PD-L1, a ligand expressed on the tumor. It is thought that interactions among PD-1 and the ligands PD-L1 or PD-L2 can lead to antitumor immune suppression; the compounds in improvement are designed to interrupt those interactions, allowing T cells to fight cancer. – See more at: http://www.onclive.com/convention-coverage/nyl-2013/PD-1-and-PD-L1-Inhibitors-Expected-to-Change-the-Landscape-of-Lung-Cancer-Treatment#sthash.nfZRBoJ5.dpuf
PD-1, an inhibitory T-cell co-receptor, or PD-L1, a ligand expressed on the tumor. It is thought that interactions among PD-1 and the ligands PD-L1 or PD-L2 can lead to antitumor immune suppression; the compounds in improvement are designed to interrupt those interactions, allowing T cells to fight cancer. – See more at: http://www.onclive.com/convention-coverage/nyl-2013/PD-1-and-PD-L1-Inhibitors-Expected-to-Change-the-Landscape-of-Lung-Cancer-Treatment#sthash.nfZRBoJ5.dpuf Anyway, Dr. Aragon-Ching responded to my email of last week asserting that Dr. Spira had told her that he was going to request that my tumor samples be sent to Foundation Medicine for testing, and that I must learn with him. I did not recall discussing that with him on Friday, so I emailed him to find out. He responded in minutes, asserting that even sooner than we met, he had requested that my tissue on file at NIH be sent to Foundation Medicine. He said it would possibly take a considerable sort of weeks to get results. I thanked him for his proactivity.
On Tuesday, February 3, the clinical trial nurse from Johns Hopkins called me to deploy an appointment together with her and the doctors participating in the trial. She invited me to satisfy together with her on Thursday to review the trial forms and solution my questions. We spent more than an hour talking concerning the trial. She confirmed that I met the clinical trial eligibility guidelines. She additionally said that the Phase I nivolumab-only cohort was closed, but that the Phase II trial was open. There are two cohorts in the Phase II trial; the first cohort gets 3 mg nivolumab and 1 mg ipilimumab every 3 weeks for four rounds, then 3 mg nivolumab only every other week thereafter. The 2nd cohort gets 1 mg nivolumab and three mg ipilimumab every 3 weeks for four rounds, then 3 mg nivolumab only every other week thereafter. In either cohort, I'd get the nivolumab drug. Patients are randomized into every one cohort, and they know which cohort they are in. She thought that I would possibly deserve to wait for the Foundation Medicine DNA test results sooner than making the final decision to go into her trial (or any other trial, for that be counted). She is tentatively holding an neighborhood for me. I have a gathering scheduled with Dr. Noah Hahn next Tuesday. Should I enroll the nivolumab trial, he would coordinate my care with Dr. Dung Le, the primary investigator.

I sent Drs. Apolo and Aragon-Ching summaries of this news, and asked no matter if the different dosages of ipilimumab would possibly put me at more desirable risk of facet effortlessly, for the reason that I had two prior rounds of cheno. They both responded that the risks need to be manageable, fantastically in moderate of my overall absence of co-morbidities and low tumor burden. Both endorsed the concept I participate in that trial.

Last Friday, Memorial Sloan Kettering called to schedule an appointment for their nivolumab trial. I told the scheduler that I was already deep into discussions with Hopkins about an equal trial. Keep us in mind in the fate, they said.

Last weekend, I did more research on nivolumab. According to the NCI drug dictionary, nivolumab is

A permanently human monoclonal antibody directed against the horrific immunoregulatory human cell surface receptor PD-1 (programmed death-1 or programmed cell death-1/PCD-1) with immunopotentiation exercise. Nivolumab binds to and blocks the activation of PD-1, an Ig superfamily transmembrane protein, by its ligands PD-L1 and PD-L2, resulting in the activation of T-cells and cell-mediated immune responses against tumor cells or pathogens. Activated PD-1 negatively regulates T-cell activation and effector operate thru the suppression of P13k/Akt pathway activation.
I learned that, in December 2104, the FDA gave approval to Bristol-Myers Squibb (BMS) for nivolumab for treatment of unresectable or metastatic melanoma. BMS's manufacturer name for nivolumab is Opdivo. The FDA press release observed that

Opdivo works by inhibiting the PD-1 protein on cells, which blocks the bodys immune gadget from attacking melanoma tumors. Opdivo is intended for patients who have been previously treated with ipilimumab and, for melanoma patients whose tumors express a gene mutation called BRAF V600, for use after treatment with ipilimumab and a BRAF inhibitor.
BMS's January 27, 2015 release of its fourth quarter and full year 2014 results trumpeted its successes with Opdivo. BMS it appears that could be spending more than $one hundred million in different Opdivo clinical trials. Some biotech stock analysts think that Opdivo is going to be a blockbuster drug for BMS, with 2020 sales projected to be more than $7 billion. Big pharma indeed.
Today I went back up to Hopkins and met with Dr. Noah Hahn, head of Hopkins' urologic oncology group. He joined JHU last April from Indiana University, and seems to be an additional brilliant advisor. Assuming I enroll into the trial, he would be for my section following my case. He seemed excited to work with a younger patient with few co-morbidities and low tumor burden — he said that most of his patients have been in their mid-70s or older and that many have been battling other complications besides cancer. I had the required screening CT scan, EKG, and blood work. I additionally met again with the clinical trial nurse, who told me that she would put up my application to enroll in the trial. She said that she expected me to be commonplace by BMS with no disorders. She would then be advised by BMS into which cohort I had been randomized. She said that she may possibly work with me on scheduling my visits, as I am alleged to be in Utah early next month for a granddaughter visit, then in late March to Florida to visit my individuals.

I feel good about this trial. As a result of my research, I have four nicely-respected oncologists endorsing my decision. I realize that the odds are low that I will have a complete reaction (e.g., all tumors shrinking to below pathological level). The odds are somewhat more desirable that I will have a partial reaction (e.g., more than 20% tumor shrinkage, but not a complete reaction), or steady disease (e.g., less than 20% shrinkage or growth). But there additionally is a 50% or more chance that my tumors won't respond, and keep growing. There is not satisfactory information about nivolumab to show long-term results, and no one is expecting it to be a "cure" (e.g., complete reaction and no subsequent tumor improvement for 5 years). But this trial seems to be the right remedy on the right time.

Leave a Reply

Your email address will not be published. Required fields are marked *