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A Study Of 4-1BB Agonist PF-05082566 Plus PD-1 Inhibitor MK-3475 In Patients With Solid Tumors (B1641003/KEYNOTE-0036)

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ClinicalTrials.gov Identifier: NCT02179918
Recruitment Status : Completed
First Posted : July 2, 2014
Last Update Posted : March 17, 2017
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Pfizer

Brief Summary:
This is a safety, pharmacokinetic and pharmacodynamic study designed to estimate the maximum tolerated dose (MTD), and determine the Recommended Phase 2 Dose (RP2D) of PF-05082566, a 4-1BB agonist monoclonal antibody (mAb), in combination with MK-3475, a PD-1 inhibitor in patients with solid tumors.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: PF-05082566 Drug: MK-3475 Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Study Of The 4-1bb Agonist Pf-05082566 In Combination With The Pd-1 Inhibitor Mk-3475 In Patients With Advanced Solid Tumors
Actual Study Start Date : August 19, 2014
Actual Primary Completion Date : February 24, 2017
Actual Study Completion Date : February 24, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: PF-05082566 +MK-3475
PF-05082566 +MK-3475
Drug: PF-05082566
Starting dose of 0.45 mg/kg q3wks IV, dose escalation

Drug: MK-3475
2 mg/kg q3wks, IV
Other Name: pembrolizumab




Primary Outcome Measures :
  1. Number of participants with Dose-limiting toxicities (DLT) [ Time Frame: First 2 cycles of treatment up to 24 months ]
    Dose Limiting Toxicities (DLTs) of PF-05082566 in combination with MK-3475.


Secondary Outcome Measures :
  1. Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 1 hr post dose of Cycles 1-4, 5, 7, 9, 11, 15, 19, 23, 27 and 31 up to 24 months ]
    Pharmacokinetic parameters of PF -05082566

  2. Anti-Drug Antibody levels of PF-05082566 [ Time Frame: 0 hr on Cycles 1, 3, 5, 7, 9, 11, 15, 19, 23, 27 and 31 up to 24 months ]
    Anti-Drug Antibody levels of PF-05082566

  3. Number of Participants With Objective Response [ Time Frame: Once every 21 days up to 24 months ]
    Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.

  4. Maximum Observed Plasma Concentration (Cmax) [ Time Frame: .5 hr post dose of Cycles 1-4, 5, 7, 9, 11, 15, 19, 23, 27 and 31 yo to 24 months ]
    Pharmacokinetic parameters of MK-3475

  5. Anti-Drug Antibody levels of MK-3475 [ Time Frame: 0 hr on Cycles 1,3, 5, 7, 9, 11, 15, 19, 23, 27, 31 and 1, 3 and 6 months post last dose up to 30 months ]
    Anti-Drug Antibody levels of MK-3475

  6. Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 1 hr. post dose on Cycles 1-4, 5, 7, 9, 11, 15, 19, 23, 27 and 31 up to 24 months ]
    Tmax of PF-05082566

  7. Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: .5 hr post dose of Cycles 1-4, 5, 7, 9, 11, 15, 19, 23, 27 and 31 up to 24 months ]
    Tmax of MK-3475

  8. Ctrough of PF-05082566 [ Time Frame: 0 hr on Cycles 1,2,3,4,5,7,9,11,15,19,23,27 and 31 up to 24 months ]
    Ctrough of PF-05082566

  9. Ctrough of MK-3475 [ Time Frame: 0 hr of Cycles 1-4, 5, 7, 9, 11, 15, 19, 23, 27 and 31 up to 24 months ]
    Ctrough of MK-3475

  10. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) PF-05082566 [ Time Frame: Cycle 5 : 0,1,2,6,24,192 and 360 hours post dose up to 24 months ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) of PF-05082566

  11. Clearance (CLss) of Study Drug of PK-05082566 [ Time Frame: Cycle 5: 0,1,2,6,24,192 and 360 hours post dose up to 24 months ]
    Steady state total body clearance equals infusion rate (zero order) divided by steady state plasma concentration of study drug (R0/Css) of PK-05082566

  12. Clearance (CLss) of Study Drug of MK-3475 [ Time Frame: Cycle 7: 0, .5, 2, 6, 24 and 192 hours post dose up to 24 months ]
    Steady state total body clearance equals infusion rate (zero order) divided by steady state plasma concentration of study drug (R0/Css) of MK-3475

  13. Volume of Distribution at Steady State (Vss) of PF-05082566 [ Time Frame: Cycle 5: 0,1,2,6,24,192 and 360 hours post dose up to 24 months ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state of PF-05082566.

  14. Volume of Distribution at Steady State (Vss) of MK-3475 [ Time Frame: Cycle 7: 0, .5, 24 and 192 hours post dose up to 24 months ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state of MK-3475

  15. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) fir MK-3475 [ Time Frame: Cycle 7: 0, .5, 24 and 192 hours post dose up to 24 months ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) for MK-3475

  16. Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] for PK-05082566 [ Time Frame: Cycle 5: 0,1,2,6,24,192 and 360 hours post dose up to 24 months ]
    AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8) for PF-05082566

  17. Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] for MK-3475 [ Time Frame: Cycle 7: 0, .5, 24 and 192 hours post dose up to 24 months ]
    AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8) for MK-3475.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histological or cytological diagnosis of advanced/metastatic solid tumor malignancy which has progressed on standard therapy or for which no standard therapy is available.
  • Measurable disease per RECIST v1.1.
  • Adequate bone marrow, renal and liver functioning

Exclusion Criteria:

  • CNS primary malignancies, active seizure disorder or spinal cord compression, or carcinomatous meningitis.
  • History of any of the following toxicities associated with a prior immunotherapy:

    • Grade 3 immune mediated adverse event that was considered related to previous immunotherapy and required immune suppressive therapy;
    • Grade 2 hepatic function related adverse event that persisted more than 1 week, was considered related to immunotherapy, or required treatment discontinuation or immunosuppressive therapy
  • Any of the following within the 12 months prior to registration: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack and 6 months for deep vein thrombosis or pulmonary embolism.
  • History of or known presence of extensive, disseminated/bilateral or Grade 3 or 4 interstitial fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, or pulmonary fibrosis, but not including a history of prior radiation pneumonitis. Patients with clinically significant lung disease requiring oxygen therapy (eg, COPD).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02179918


Locations
United States, California
UCLA Department of Medicine, Division of Hematology/Oncology
Los Angeles, California, United States, 90024
Ronald Reagan UCLA Medical Center, Drug Information Center
Los Angeles, California, United States, 90095
UCLA Bowyer Clinic
Los Angeles, California, United States, 90095
UCLA Hematology-Oncology Clinic
Los Angeles, California, United States, 90095
United States, Connecticut
Smilow Cancer Center at Yale New Haven Hospital
New Haven, Connecticut, United States, 06510
Smilow Cancer Hospital at Yale-New Haven
New Haven, Connecticut, United States, 06510
United States, Texas
South Texas Accelerated Research Therapeutics, LLC (START)
San Antonio, Texas, United States, 78229
South Texas Accelerated Research Therapeutics, LLC
San Antonio, Texas, United States, 78229
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
University of Washington Medical Center
Seattle, Washington, United States, 98195
Sponsors and Collaborators
Pfizer
Merck Sharp & Dohme Corp.
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02179918     History of Changes
Other Study ID Numbers: B1641003
KEYNOTE-0036
First Posted: July 2, 2014    Key Record Dates
Last Update Posted: March 17, 2017
Last Verified: March 2017

Keywords provided by Pfizer:
Advanced Solid Tumors

Additional relevant MeSH terms:
Pembrolizumab
Antibodies, Monoclonal
Immunoglobulin G
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs