New trial for anti-PD1

 All I've done is copy and paste.  Hope it helps. - c

 

Phase 1 Biomarker Study of Anti-PD-1 in Advanced Melanoma

Verified by: Bristol-Myers Squibb, June 2012
First Received: June 14, 2012 | Last Updated: June 15, 2012
Phase: Phase 1 | Start Date: September 2012
Overall Status: Not yet recruiting | Estimated Enrollment: 80

Brief Summary

Official Title: “An Exploratory Study of the Biologic Effects of BMS-936558 (Anti-PD-1 Monoclonal Antibody) Treatment in Subjects With Advanced Melanoma (Unresectable or Metastatic)”
The purpose of this study is to evaluate pharmacodynamic changes of BMS-936558 treatment on the biomarkers measured in the peripheral blood and tumor tissues of subjects with advanced melanoma (unresectable or advanced).

• Study Type: Interventional
• Study Design: Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science
• Study Primary Completion Date: December 2015

Interventions Used in this Clinical Trial

• Biological: BMS-936558 (Anti-PD-1)
  • Solution, Intravenous infusion, 3 mg/kg, Every 2 weeks, Up to 2 years depending on response

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Arm 1: BMS-936558 (3 mg/kg)

Outcome Measures for this Clinical Trial

Primary Measures

• Immunomodulatory effects of BMS-936558 as measured by changes from baseline in activated and memory T cells, interferon, interferon inducible factors, and CD4 and CD8 T cell infiltration
  • Time Frame: Pre-dose day 1
    Safety Issue?: No
• Immunomodulatory effects of BMS-936558 as measured by changes from baseline in activated and memory T cells, interferon, interferon inducible factors, and CD4 and CD8 T cell infiltration
  • Time Frame: Up to day 57 (Cycle 2 Day 1)
    Safety Issue?: No

Secondary Measures

• Safety and tolerability of BMS-936558 as measured by the incidence of adverse events (AEs), serious AEs, death, and changes in vital signs
  • Time Frame: Up to 14 weeks after last dose of study drug
    Safety Issue?: Yes
• Safety and tolerability of BMS-936558 as measured by laboratory test abnormalities
  • Time Frame: Every 2 weeks up to 14 weeks after last treatment
    Safety Issue?: Yes
• Antitumor Activity of BMS-936558 as measured by the objective response rate (ORR), duration of response, and progression free survival (PFS)
  • Time Frame: Every 8 weeks until confirmed disease progression and in follow-up if no progression
    Safety Issue?: No
• Immunogenicity of BMS-936558 as measured by the frequency of subjects with at least one positive ADA assessment and the frequency of subjects who develop anti-drug antibodies (ADA) after a negative baseline assessment
  • Time Frame: Day 1, Day 15, Day 43 of cycle 1, Day 1 of cycle 2, Day 15 of cycle 3, every 16 weeks after cycle 3 Up to 2 years, and at Follow-up visits 1 (49±3 days after last treatment) and Follow-up visit 2 (90-120 days since last treatment)
    Safety Issue?: Yes
• Association between Programmed cell death ligand 1 (PD-L1) and clinical efficacy will be measured by PDL1 expression levels clinical activity (ORR, PFS)
  • Time Frame: Pre-dose Up to Day 1 (screening) and Day 29 of cycle 1
    Safety Issue?: No

Criteria for Participation in this Clinical Trial

Inclusion Criteria

• Men and women > 18 years
• Eastern Cooperative Oncology Group (ECOG) status = 0 to 1
• Subjects with unresectable Stage III or IV melanoma who are either refractory or intolerant to, or have refused standard therapy for treatment of metastatic melanoma
• Subject must have histologic or cytologic confirmation of advanced melanoma
• Subjects must have at least one measurable lesion at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
• Subjects must have at least 1 tumor site that can be biopsied at acceptable clinical risk and must consent to pre- and post-treatment biopsies

Exclusion Criteria

• Active or progressing brain metastases
• Other concomitant malignancies (with some exceptions per protocol)
• Active or history of autoimmune disease
• Positive test for human immunodeficiency virus (HIV) 1&2 or known acquired immunodeficiency syndrome (AIDS)
• History of any hepatitis
• Prior therapy with any antibody/drug that targets the T cell coregulatory proteins, including but not limited to, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40,and anti-CD40 antibodies. However, half the patients must have progressed on anti Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA4) monoclonal antibody therapy

Gender Eligibility for this Clinical Trial: Both
Minimum Age for this Clinical Trial: 18 Years
Maximum Age for this Clinical Trial: N/A
Are Healthy Volunteers Accepted for this Clinical Trial: No

Clinical Trial Investigator Information

Lead Investigator: Bristol-Myers Squibb Industry

Overall Clinical Trial Officials and Contacts

Bristol-Myers Squibb, Study Director, Bristol-Myers Squibb

Additional Information on this Clinical Trial

Information obtained from ClinicalTrials.gov on June 27, 2012
Link to the current ClinicalTrials.gov record. – http://clinicaltrials.gov/show/NCT01621490
Study ID Number: CA209-038
ClinicalTrials.gov Identifier: NCT01621490
Health Authority: United States: Food and Drug Administration

Source

Clinical Trials content is provided directly by the US National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of information about a specific clinical trial contains a unique identifier which can be used to find further details directly from the National Institutes of Health.
The URL of this page is:
http://clinicaltrialsfeeds.org/clinical-trials/show/NCT01621490

It's gett'n hot in here!!!!!

Whoa, Nelly!!! 102 degrees in the valley yesterday and 96 up here on the mountain!  What the tub????  With crazy 106-108's predicted for Chatt-town and Dalton this weekend! What was that about global warming being a figment of the founder of the internet's imagination??!  (I admit Gorpy Gore has a great imagination, but he was just a mouthpiece, folks.  Think...SCIENCE....here!!!)

And a big HANDS IN THE AIR to SCOTUS!!!!!!  The robes are feeling the heat today!  But, thank goodness Robert's seizures must have affected his brain...in a good way!  This is an amazing victory for every person with melanoma, other cancer, or chronic disease!  I can now get insurance of my own...NO PRE-EXISTING denials...should B retire!!!  I happened to be riding on his family plan when the shit came raining down and if I were to lose that before 2014...well....I'd just be shit out of luck...AGAIN!!!!  And then, there's all the people who max out their insurance policies.  Sadly, most folks don't even realize this can happen...til it does.  Every policy (before now) had a lifetime amount of dollars to be spent for your care.  I have witnessed this so many times with good, hard working families who have insurance....and one premature baby.  Heavy duty intensive care and a few surgeries later and they have a child with significant healthcare needs and no money with which to pay for them.  The parents have jobs.  They, and the rest of the family, even have "good" insurance.  But, the child....now maybe 2-4 years in age...has maxed out their allotted dollars....no insurance for you, baby girl.  Can you imagine?  That's how it's been.  I will spare you my droning on about all the other sad predicaments everyday folks find themselves in that the institution of these healthcare changes can help ameliorate.  Nor will I spend this moment being hot and bothered by the MILLIONS of AMERICANS who will remain on the fringe, without adequate care, because of the deficits that remain in our healthcare policy.  Rather....

....I ask you to celebrate a hot, happy day with a cool drink....and be proud you live in a country that has taken steps in the right direction, to help each American in need of basic preventive care and medical attention, acquire the health care they deserve. 

And, Hey!  If you get the musical reference here....the drink's on me!!!  Off for more early morning berry picking....and a toast:  To your health!!!! - c

Side effects this go round...

...have not been too bad. Some mouth tenderness and sensitivity with only a couple of mild lesions to the tongue have been a bit of an aggravation.  The biggest difficulty this time has been pain in my hands, wrists, and elbows.  At first it was enough to wake me from sleep, but now it is just a bit dull and achy.  Brent has been pushing ibuprofen...given the NSAID report, perhaps it will work double duty!!  HA!  Nevertheless, I have been doing my usual 12-hour shifts that a pediatric office has when there is an outbreak of viral gastro and high fevers in early summer combined with general pediatric chaos. I am very proud to report that, additionally, I have managed to run, bike, do core and/or Insanity workouts EVERY off day since treatment.  So there...Anti-PD1....you can put THAT in your pipe and smoke it!!!!

On top of that, B and I have been busy bees this weekend, prepping veggies for the coming week, doing yard work, catching up on other chores.  AND...we are very proud that yesterday we were able to pick more than 3 cups of blueberries from our own bushes and this morning we picked 16 cups of blackberries that grow in generous abundance just down the road!

Enjoy the fruits of your labors! - c

Dead men tell no tales...

The Battle of Chickamauga: 
Rosecrans and Thomas...US vs Bragg and Longstreet...Confederate

As the Civil War dragged on, Rosecrans wanted Chattanooga for the Union...a gem in the south with its rail lines running to Nashville, Knoxville, and Atlanta; access to river traffic on the TN; and as a manufacturing center for iron and coke...Chattanooga was much desired by both sides.  In September of 1863, he gathered Union troops scattered in TN and north GA and pushed Bragg out of Chattanooga, headed south.  Bragg was equally determined not to lose Chatt-town for the rebels.  On the 17th, Bragg headed north again.  On the 18th, he ran into Union Calvary and mounted infantry. Fighting grew more intense on the 19th as Bragg continued to hammer, but failed to break through the Union line strung out between LaFayette and Rossville, GA. On Sept 20th, Bragg continued his assault.  A break came for the Rebels, when Rosecrans was told, in error, of a break in his line.  As Rosecrans maneuvered troops to fill the supposed gap, he created one, which Longstreet promptly exploited, driving 1/3 of the Union Army, including Rosecrans, from the field.  After a small rally, the Union retired to Chattanooga with the Confederates occupying the surrounding high ground of Missionary Ridge and Lookout Mountain.

This nifty interlude of back and forth in our country's history required the lives of 3,969 men and wounded 24,430 more.  I wonder what all those boys from Illinois and Ohio thought of the thick woods, swampy creeks, and sharp ridges in TN and North GA. 

All this comes to me because yesterday, Brent and I biked over two hours through the Chickamauga Battlefield.  Today, there are large open fields and wooded paths filled with deer, chipmunks, squirrels, robins, doves, mocking birds....and that's just what we saw....living among the white, marble monuments depicting battle lines, skirmishes, and death.

We were there to check out the path of a Marathon/1/2 Marathon coming up in November that Brent is thinking of running in.  It was a beautiful day (if hotter than big, hairy Wizard balls!!!...Thanks, Ruthie!!!) and when biking on paths in the deeper woods, it was surprisingly cool.  We were only incredibly lost twice.  Once we were spontaneously rescued by a young, local guy in his pickup who patiently turned us around and got us headed in the right direction.  And later, by a Yank (given his distinct, clipped accent!) all decked out on a fancy bike, shaved and everything like a serious biker....stopping his dedication to his sport to help us pick the desired fork. (No proper spandex or titanium Schwinn bikes for us!!!)

And perhaps, that says it all.  A south Alabama girl and  hometown Chattanooga boy, with tendencies to wander globally, rescued by both sides.  A beautiful place, forever haunted by men and boys who will speak no more.  May we all live such that our deeds and those who love us will speak well of us in the end. - c

Happy Birthday, Fred-o!!!!!

I can't begin to understand how I got to be so lucky as to be your mommy!  So many happy memories of the chubbiest, jolliest baby in the entire world!!!!  And now, the consistently gooey boy, with hands that usually held some critter or other, is a handsome man....with skills!!!!  Your ability to laugh and deal with others will always take you far.  Thanks for sharing your life with me.  I can't wait to see where you go.  HAPPY BIRTHDAY, BABY!!! - mommy

New trials for Melanoma NED patients....

...are almost non-existent!  While it is obvious that Stage IV melanoma patients with non-resectable disease are in immediate need of treatment....it is equally clear to me that if you don't treat the Stage IV NED melanoma patients, they will soon join the crowd!  When I began the trial I am in...there was absolutely nothing else available to me.  And once again...as my trial begins to head down its final stretch, there is very little out there for folks in my shoes.  Much of this deficit comes from the fact that when you treat me....what have you learned?  My results are hard to calculate....and hard for drug companies to sell.  I did not have measurable disease at the start, so no one can tout a grand success story of decreased or eradicated tumors that show up on scans one minute and recede in the next.  Additionally, there is no "standard of care" treatment option for NED patients other than interferon and you all know what I (as well as most of the entire melanoma research community) think of that by now.  SO.....what to do???  Unfortunately...most of the drug companies...who are (sadly) the main drivers of such research...say...not much.

Brent and I read of a trial that may be starting for Stage III, resected, offering arms of ipi vs interferon, with or without kinase inhibitors.  It seems rather unconscionable to me...but again, because there is no standard "adjunctive" treatment option other than interferon...they can get away with it. I am sorry that I know no other information on that trial.

However, Brent and I were told the following Friday:  Moffitt will be participating in a "300 patient, international, NED trial" that will be a double blind study with patients receiving either BMS anti-PD1 or "observation" with placebo.  This means that every three months you will have to have scans, and blood drawn, and infusions...but you may be getting the drug or not.  This is the shit of a phase three trials....you might get something...or you might get nothing.  The shit of phase one trials (like mine) is that people may be giving you poison that will make you sprout three heads, but at least you know you are getting it.  I don't know if these will be Stage III or only Stage IV NED patients.  I don't know when it will start. I don't know if all the patients will have to travel to Moffitt, or if Moffitt is only one of multiple centers that will be participating.  I wish I could give more information...but when we are there...we try to absorb as much as we can from those in the know....and sometimes it is so rapid fire that we come out with more questions than answers.  At any rate....it is something...and if you are interested, I would definitely recommend that you call Moffitt for additional information.

Wishing all of you my very best - c

Additonal info on MDX-1106 OR BMS-936558

On May 20th I blogged my on take on the abstract of an article talking about the BMS version of anti-PD1.  The article was finally published on June 2, 2012 in the New England Journal of Medicine...Safety, Activity, and Immune Correlates of Anti-Pd1 Antibody in Cancer.  Written by the same cast of characters already noted.

Though the final article has slightly different numbers (due to the final accounting of patients and their results, rather than the arbitrary cut-off in the abstract)....Bottom line: 296 patients with a variety of cancers (94 with melanoma) were treated every 2 weeks for for up to 2 years at dosages of 0.1 to 10 mg/kg. Patients with non-small-cell lung cancer, melanoma, and renal-cell cancer demonstrated some response.  Patients with prostate and colon cancer did not.  All these patients were very ill and "the majority of patients were heavily pretreated; 47% had received at least three prior treatment regimens."  A maximum dose was not defined and researchers deemed the drug well tolerated (PER RESEARCHERS!!!!!  though the dead people and those suffering with side effects may not agree!!!!!), though "15 of the 296 patients discontinued treatment owing to treatment related adverse events....As of the date of analysis, 62 patients (21%) had died; disease progression was the most common cause of death....[though] there were three drug-related deaths (1%) due to pneumonitis..."  Some patients at all drug dosage levels experienced a response, indicating that as yet...we do not know the most effective dose.  Response seems to be durable for some patients....at times lasting greater than one year at publication.

However, perhaps the biggest news from the study/article is the significance of the presence of PD-L1 in the tumors of patients treated.  "61...tumor specimens from 42 patients (18 melanoma, 10 lung cancer, 7 colorectal cancer, 5 renal cell, and 2 with prostate cancer) were analyzed for  PD-L1 expression on the surface of tumor cells."  25 of the 42 patients had tumors that were positive for PD-L1. "Of these 25 patients, 9 (36%) had an objective response.  NONE of the 17 patients with PD-L1 negative tumors had an objective response.....These preliminary results must...be interpreted with caution."  However, the presence (or absence) of such bio-markers may play a huge role in the identification of candidates for anti-PD1 treatment and guide disease management decisions.

So, it would seem that if you have PD-L1 on the surface of your tumor....you have a 36% chance of a response to the BMS anti-PD1 product.  That number is better than the 30% chance that is showing up in most of the anti-PD1 data (limited though it is) thus far.  On the flip side, if you do not have that particular ligand...it appears that it is extremely unlikely that anti-PD1 therapy will help you at all.  To that end...BMS is taking this info very seriously.  They are paying for all the patients at Moffitt, in my study, to have their tumors tested for that very biomarker.  You do not have to agree to this testing to remain in my study, but they are requesting it of all of us, and I signed the agreement for mine to be tested Friday.  For those of us in the study, it is of no consequence.  We either have it or we don't.  We have already been treated and we will respond or we won't.  But, perhaps our data will help others.  First:  We need to see if this data holds.  Second:  If it does, perhaps it will help others make better treatment choices.  If this is true, and anti-PD1 cannot help you if your tumor does not express PD-L1, there is no need for you to waste precious time, money, and risk significant side effects seeking this particular treatment.  Obviously, time will tell....hopefully progress and knowledge will be attained soon. - c