Expanded Access for PD-1--Great News!

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3/10/2014 6:08pm
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Replies: 23

Merck is launching an expanded access program for their anti-PD1 drug lambrolizumab. Clinical trials have shown very positive results for this drug, with response rates significantly higher than any drug currently approved for melanoma.

Here are the key points:

·  The program will initially be available at sites in the United States that have been involved in the Merck PD-1 trials. Fairly quickly it will be made available to other physicians in the US who have experience treating melanoma with immunotherapy. After that, the expansion will extend globally.

·  It is open to all patients with advanced melanoma, with no exclusion for ocular, mucosal, or acral melanoma.

·  Patients with brain mets are allowed if the brain mets have been treated. The mets do not have to be resolved, but some treatment must have been given.

·  Patients in previous Merck PD-1 trials are not eligible. This includes patients who have been in the head-to-head study of Merck’s PD-1 drug vs. ipilimumab.

This is just being announced to clinicians and I don't believe it is live yet on Clinicaltrials.gov.  That should happen within the next few hours and will include a number doctors can call to get more information.

Here is the process: The doctor will hear about and enroll in the program. The clinician's Institutional Review Board (IRB) will need to approve the program; generally 2 to 3 days. Then patients can start being evaluated for eligibility. 

This is great news for melanoma patients, particularly since a lot of PD-1 trials are currently closed.

 

Tim--MRF

 

 

 

 

So will this be on a single subject basis at first then go to a protocol for facilites that were not associated with the trial??

Thanks, Tim.    I'm feeling like this is "it". It might not be. But it might!

Don't Stop Believing

Anonymous - (3/10/2014 - 7:16pm)

Tim,

 

Thank you for sharing this great info. I have a relative that  was in the Curetech pd1 trial who progress on that trial.

Many people progressed on that trial so that it is questionable how effective Curetech pd1 is.

Will people who progressed on Curetech PD1 trial be allowed to get Merck pd1 drug?

 

Thanks

Ann

 

Anonymous - (3/10/2014 - 7:55pm)

This is really great news, and apparently it means those of us who failed the Curetech "PD1" trial (wasn't that everyone??) will not be excluded. At least, this is what has been reported a couple of hours ago on the Melanoma International Foundation forum by Catherine Poole. She reports that "other anti-PD1" failures are not exclusions. You may want to verify that with her, since it's not clear from the Merck release.

Ann:

The only exclusion around previous PD-1 is for people who have progressed on Merck's drug. Those who have progressed on PD-1 drugs from other companies will be eligible.

 

Tim--MRF

Here is the clinical trial NCT02083484 published at clinicaltrials.gov: "Program for MK-3475 in Participants With Metastatic Melanoma Who Have Failed Standard of Care Therapy Including Ipilimumab (MK-3475-030)"

Inclusion criteria:

  • Unresectable (Stage III) or metastatic melanoma
  • Failed or progressed on standard of care systemic therapy including ipilimumab
  • Willing to sign Informed Consent
  • Eastern Cooperative Oncology Group Performance status of 0 or 1
  • Female participants of childbearing potential must be willing to use adequate contraception or be surgically sterile, or abstain from heterosexual activity starting with the first dose of treatment through at least 120 days after the last dose of MK-3475
  • Male participants must agree to use an adequate method of contraception starting with the first dose of treatment through 120 days after the last dose of MK-3475
  • Adequate organ function

Exclusion criteria:

  • Eligible for an accessible MK-3475 clinical study or previously participated in a MK-3475 clinical study
  • Eligible for treatment with a marketed BRAF/MEK inhibitor
  • Not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better due to prior chemotherapy, radioactive, or biological cancer therapy (including monoclonal antibodies)
  • Not recovered from minor or major surgery and less than 4 weeks from major surgery
  • History of life-threatening or severe immune-related adverse events on treatment with another immunotherapy
  • Expected to require any other form of systemic antineoplastic therapy while receiving MK-3475
  • History of clinically severe autoimmune disease (e.g., requires chronic immunosuppressive therapy)
  • History of pneumonitis, organ transplant, human immunodeficiency virus (HIV), active hepatitis B or hepatitis C
  • Active central nervous system metastases, carcinomatous meningitis, untreated brain metastases
  • Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of treatment with MK-3475
  • Active infection requiring systemic therapy

This is great news to hear!!  I've had good results with Merck's pd1 so far.  Scans on Monday the 17th and dose #21 on the 20th...  with minimal side effects.

Thanks,
Erin

www.melanomaandthecity.blogspot.com

"people will forget what you said, people will forget what you did, but people will never forget how you made them feel' Maya Angelou

Anonymous - (3/11/2014 - 1:08pm)

An exclusion criterion is: "Eligible for treatment with a marketed BRAF/MEK inhibitor"?? Does that mean that no one who is BRAF positive is elegible for this Expanded Access program unless and until they fail BRAF+MEK?  Aren't there studies that show that once you have failed BRAF, the disease progresses so quickly that there often isn't time for a checkpoint inhibitor like anti-PD1 to work? Am I not understanding something here?

Yeah. My thoughts exactly. I hope someone can answer that.

My understanding is you have to failed a braf inhibitor or ipi or a combo of the two

Anonymous - (3/11/2014 - 9:49pm)

The criteria posted above say that you are EXCLUDED from getting anti-PD1 on the expanded access program if you are ELIGIBLE for BRAF+MEK. That means that you MUST take BRAF + MEK first (if you can) before you can apply for the EAP.  

Under Exclusions It doesn't say you must have failed BRAF monotherapy, it says you must first try (and presumably fail)  BRAF+MEK. At least that is my reading of the criteria.

Anonymous - (3/12/2014 - 7:53am)

Catherine Poole of the Melanoma International Foundation is very "up" on the clinical trial picture. She posted today that to be elegible for the anti-PD1 EAP you must have tried and failed a BRAF inhibitor. The MEK really has nothing to do with it. According to Catherine, you must have tried Zelboraf OR Tafinlar OR Tafinlar + Mekinist. 

Yes, Eric, that is pretty much what you said, but I needed to nail down the grammar. ;-( The way I was reading the criteria, I was afraid that if you haven't tried the combo (Tafinlar + Mekinist) you have to do that before applying for the ADP program. That is not true. 

Awesome. Thank you so much. I tried and failed Zelboraf. For 2 weeks I did Tafinlar + Mekinist and now doing radiation then am supposed to start doing Tafinlar + Mekinist again.

Sounds like I don't have to wait for it to fail too. That is really really great news. Thank you.

 

Anonymous - (3/15/2014 - 7:56pm)

what is :Common Terminology Criteria for Adverse Events (CTCAE) Grade 1. I searched online and didn't find anything?

Anonymous - (3/15/2014 - 10:51pm)

 

Side effects are technically called "adverse events".Grade refers to the severity of the adverse event (AE).

The CTCAE v3.0 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline:

Grade 1 Mild AE

Grade 2 Moderate AE

Grade 3 Severe AE

Grade 4 Life-threatening or disabling AE Death related to AE

Grade 5 Death related to AE

Yes, this is tremendous news!

Tina

Hey Tim,

 

My wife is seen at UCLA and we talked to them yesterday about this. They indicated that the whole process for the protocol will take around 2-3 months. Curious if this will be the norm for most facilities? Thanks

FYI - A Houston site (St. Luke's) is starting right away.  However, they could not get my mother on the expanded access protocol because she had not taken ipi, which her main oncologist said would be too toxic for her (she is elderly and has lots of liver mets).  Please help get Merck to open up the protocol to Stage IV patients with very short time horizons. 

Cynthia

We are in Canada, waiting for pd1 here.... Any idea when it might be available here? Also, I am wondering if anyone knows if we as Canadians can travel state-side to get  the drug?

Shauna

Anonymous - (3/15/2014 - 7:53pm)

Tim,

Please clarify the brain mets issue. The Merck site says no one with active central nervous system metasteses can get Merck 3475 but you say they can as long as they have been treated. This is critical in my husband's case as all the tumors are in his brain. He finsihed Yervoy one month ago. Current MRI shows some tumors shrank, some are stable, and some 'grew'. Or is it pseudo-progression??

 

Anonymous - (3/15/2014 - 10:53pm)

What is "pseudo-progression"? I never heard of that.

In my reading, some say that Yervoy can cause 'pseudo-progression' so scans can look worse before they get better (if they get better). Because Yervoy can ramp up the immune system, immune activity can go into the tumors and make them bigger. This is a very simple way of stating. it.

Happy Easter!

 

My sister Marsha has Stage IV melanoma cancer in her liver.  She hasn't
started treatment yet but is scheduled April 28th for IL2.  We noticed a
clinical trial that you posted from Merck thats with the ANTIPD1.  My sister
has the KRAS mutation and I want to see how we can possibly get her on this
clinical trial.  Can anyone provide me on what steps I need to take to get her
DR. to provide us with the info/etc.

She's 46
Healthy, 118/ 5'3.  No other comorbidities.

Husband also has Stage IV Melanoma so you can imagine we are really bummed.  

 

Any advice would be so helpful as time is ticking

Best,
Jennifer
jennyjcure@gmail.com