Long-term Safety And Effectiveness Study For Participants With Advanced Tumors Who Are Currently On Treatment Or In Follow-up In A Pembrolizumab Trial

Overview

About this study

The purpose of this study is to evaluate the long-term safety and efficacy of pembrolizumab (MK-3475) in participants from previous Merck pembrolizumab-based parent studies who rollover into this extension study.

This study will consist of three phases: 1) First Course Phase, 2) Survival Follow-up Phase or 3) Second Course Phase.

Each participant will roll-over to this extension study in one of the following three phases, depending on the study phase they were in at the completion of the parent study.

Participants who were in the First Course Phase of study treatment in their parent study will enter the First Course Phase of this study and complete up to 35 cycles of study treatment with pembrolizumab or a pembrolizumab-based combination.

Participants who were in the Follow-up Phase in the parent study (post-treatment or Survival Follow-up Phase) will enter the Survival Follow-up Phase of this study.

Participants who were in the Second Course Phase in their parent study will enter Second Course Phase of this study and complete up to 17 cycles of study treatment with pembrolizumab or a pembrolizumab-based combination.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Participants that are currently enrolled in MSD-sponsored pembrolizumab trials and are receiving trial treatment or in a Follow-up Phase at the time KN587 is open. The parent trials must have completed all regulatory requirements and submissions, if any, or have fully addressed their primary endpoint(s) before all of their participants roll over into KN587.

  • The participant (or legally acceptable representative if applicable) provides informed consent for the trial and agrees to follow study procedures.

Exclusion Criteria:

  • There are no exclusion criteria to participate in MK-3475-587.

Additional eligibility criteria for participants who enter Second Course Phase once they are enrolled on KN587:

  • Did not receive any anticancer systemic treatment since the last dose of pembrolizumab or a pembrolizumab-based combination in First Course Phase.

  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

  • Demonstrate adequate organ function below:

System | Laboratory Value

  • Hematological

    • Absolute neutrophil count (ANC) |  ≥1500/μL ≥ 1000/μL (hematological malignancies)

    • Platelets ≥ 100 000/μL | ≥ 75 000/μL (hematological malignancies)

    • Hemoglobin ≥.0 g/dL or ≥.6 mmol/La ≥8.0 g/dL or ≥5.0 mmol/La (hematological malignancies)

  • Renal

    • Creatinine OR 

    • Measured or calculatedb creatinine clearance | ≤ 1.5 × ULN OR

    • (GFR can also be used in place of creatinine or CrCl) | ≥ 30 mL/min for participants with creatinine levels >1.5 × institutional ULN

  • Hepatic

    • Total bilirubin | ≤ 1.5 × ULN OR direct bilirubin ≤ LN for participants with total bilirubin levels | >1.5 × ULN

    • AST (SGOT) and ALT (SGPT) | ≤ 5 × ULN (≤ × ULN for participants with liver metastases)

  • Coagulation

    • International normalized ratio (INR) OR prothrombin time (PT) | ≤ 1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

    • Activated partial thromboplastin time (aPTT)

  • ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal.

    • Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion

    • within last 2 weeks.

    • Creatinine clearance (CrCl) should be calculated per institutional standard.

    • Note: This table includes eligibility-defining laboratory value requirements for Second Course Phase trial treatment; laboratory value requirements should be adapted according to local regulations and guidelines for the administration of specific chemotherapies.

  • Have resolution of any toxic effect(s) of First Course Phase trial treatment with pembrolizumab or a pembrolizumab-based combination to Grade 1 or less (except alopecia) before trial treatment in Second Course Phase is started. If participant received major surgery or radiation therapy of > 30 Gy, they must have recovered from the toxicity and/or complications of the intervention.

  • Male participant must agree to use contraception as detailed in Appendix 2 of this

  • protocol during the Second Course Phase trial treatment period and for at least

  • 120 days, corresponding to time needed to eliminate any trial combination

  • treatment(s), plus 75 days (a spermatogenesis cycle) for trial treatments with

  • evidence of genotoxicity at any dose after the last dose of trial treatment and

  • refrain from donating sperm during this period.

  • A female participant is eligible to enroll if she is not pregnant (see Appendix 2,

  • not breastfeeding, and at least one of the following conditions applies: A woman

  • of childbearing potential (WOCBP) who agrees to follow the contraceptive

  • guidance in Appendix 2 during the trial treatment period and for at least 120 days

  • (corresponding to time needed to eliminate any trial combination treatment(s) plus

  • 30 days (a menstruation cycle) for trial treatments with risk of genotoxicity.

Participants are excluded from entering Second Course trial treatment once they are enrolled on KN587 if any of the following criteria applies.

  • Note: all procedures related to eligibility for Second Course Phase trial treatment should be entered into the database.

Medical Conditions

  • WOCBP who has a positive urine pregnancy test within 72 hours prior to trial treatment allocation (see Appendix 2). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

    • Note:  in the event that 72 hours have elapsed between the pregnancy test and the first dose of trial treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for participant to start receiving trial treatment.

  • Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients (the list of excipients is provided in the IB).

Prior/Concomitant Therapy

  • Has received a live vaccine within 30 days prior to the first dose of Second Course Phase trial treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.

Diagnostic Assessments

  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the Cycle 1 Day 1 of Second Course Phase.

  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early stage cancers (carcinoma in situ or Stage 1) treated with curative intent, melanoma (non-ulcerated, thin primary), basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy.

  • Has known active central nervous system metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may enroll provided they are asymptomatic, not requiring the use of steroids at doses >10 mg/day prednisone or equivalent and have recovered adequately from the complications and/or toxicity of surgery or radiotherapy if required for their management.

  • Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.

  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. Note: Participants that experienced pneumonitis during First Course that did not meet the criteria for permanent discontinuation are eligible.

  • NSCLC participants only: Has interstitial lung disease.

  • Has an active infection requiring systemic therapy.

  • Has a known history of human immunodeficiency virus infection.

  • Has a known history of or is positive for hepatitis B (hepatitis B surface antigen reactive) or hepatitis C (hepatitis C virus RNA [qualitative] is detected).  Hepatitis C lab testing is allowed for eligibility purposes in countries where hepatitis C virus RNA is not part of SOC.

  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the Second Course Phase eligibility visit through 120 days after the last dose of trial treatment.

  • Has severe cardiovascular disease, ie,arrhythmias, requiring chronic treatment, congestive heart failure (New York Heart Association Class III or IV) or symptomatic ischemic heart disease.

  • Has hepatic decompensation (Child-Pugh score > 6 [class B and C]).

  • Has uncontrolled thyroid dysfunction.

  • Has uncontrolled diabetes mellitus.

  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's enrollment for the full duration of the trial, or is not in the best interest of the participant to enroll, in the opinion of the treating investigator.

  • Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the trial (specific testing is not required).

  • Has had an allogeneic tissue/solid organ transplant.

  • Has a known history of active tuberculosis (TB; Bacillus tuberculosis).

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Matthew Block, M.D., Ph.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

International patient clinical studies questions