Wednesday, March 12, 2014

Expanded Access Program for Merck's anti-PD1 (MK-3475/Lambrolizumab) from my thoughts and questions

Program for MK-3475 in Participants With Metastatic Melanoma Who Have Failed Standard of Care Therapy Including Ipilimumab (MK-3475-030)

Expanded access is currently available for this treatment.
Verified March 2014 by Merck Sharp & Dohme Corp.
Sponsor:  Merck Sharp & Dohme Corp. Identifier:  NCT02083484
First received: March 7, 2014
Last verified: March 2014 

This is an expanded access program (EAP) for participants who have progressed after prior systemic therapy including ipilimumab, and V-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor or mitogen-activated protein kinase (MEK) enzyme inhibitor when indicated. Participants cannot be eligible for or have participated in any MK-3475 clinical trial.

Biological: MK-3475

Study Type:
Expanded Access     [EXPANDED ACCESS =A process regulated by the Food and Drug Administration (FDA) that allows manufacturers to provide investigational new drugs to patients with serious diseases or conditions who cannot participate in a clinical trial.
For more information on expanded access programs, please visit the FDA Web site at ]
Official Title:
Expanded Access of MK-3475 in Metastatic Melanoma Patients With Limited to No Treatment Options
Intervention Details:
Biological: MK-3475
Each participant will receive MK-3475 every 3 weeks for up to 2 years or until confirmed radiographic disease progression, unacceptable toxicity, confirmed positive pregnancy test, withdrawal of consent, or MK-3475 approval in the participant's country.
Ages Eligible for Study:  
12 Years and older
Genders Eligible for Study:  

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
Contacts and Locations:  Please refer to this study by its identifier: NCT02083484  Contact:  1-855-478-43471-855-478-4347

1.  This is good news.  Anytime a drug that has a positive effect is available for more folks in need, that is a very good thing indeed.
2. In the pandemonium that has surrounded this announcement it is important to remember what studies show this drug can offer.  In Merck's first Phase 1B study with this anti-PD1 product, once follow-up data was added, overall response rate was 41%, with 88% of patients who demonstrated partial or complete responses, showing no evidence of disease progression.
3.  For what it is worth, Dr. Weber, who is currently running trials with both the BMS and Merck anti-PD1 drugs, feels that they will both pan out with approximately the same overall results.
1.  Exclusions include - "history of life-threatening or severe immune-related adverse event" on prior immunotherapy.   Who decides?  Is an admission for colitis on ipi, though now recovered, considered a "severe immune-related adverse event"?  Is ipi induced hypothyroidism?
2.  I assume that "failed or progressed on standard of care systemic therapy including ipi"  also includes IL2?  other anti-PD1 products? (Various folks on the forums are saying that failing anti-PD1 products other than Merck's allow inclusion, though it is not clearly stated here.)
3.  If BRAF positive, it seems that you must go ahead and use that option, then fail/progress in order to gain access to MK-3475.  Would this be something I wanted to do first, if I had minimal disease burden?  I don't know the answer to that.  But, I think it would be a hard thing for me to decide.
4. Since not explicitly stated, must one have failed on ALL of the above?  If you have one of these "systemic therapies" left untried, must you do, say...IL2, before you can gain access?  Even though you failed ipi and BRAF?
5.  An additional exclusion, is if you are "eligible for an accessible MK-3475 clinical study."  Does this mean that if there were a study with MK-3475 vs say...dacarbazine...and you got the dacarbazine are stuck with that and ineligible for expanded access?  What is accessible?  If there is an expanded access option within 30 minutes of your home, but an MK-3475 trial slot open several hours away....must you take the trial slot?
6.  Who will pay for the drug?  I am not saying there will be a charge, but it doesn't say there will NOT be, either.  The company could petition the FDA for the ability to charge the patient. Additionally, will facilities providing the drug charge the patient? Again, they could petition the FDA as well.  You can check the links below for additional info.

Hopefully the answers to these questions will be clarified very soon and patients with few remaining options will be given another viable solution!!!
Fingers crossed - c

No comments:

Post a Comment