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A Study of PF-05082566 In Combination With Mogamulizumab In Patients With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT02444793
Recruitment Status : Terminated (The study was terminated due to marginal efficacy and change in sponsor prioritization. The combination had a manageable safety profile.)
First Posted : May 14, 2015
Last Update Posted : April 25, 2018
Sponsor:
Collaborator:
Kyowa Hakko Kirin Co., Ltd
Information provided by (Responsible Party):
Pfizer

Brief Summary:
This study is a Phase 1b, open label, multi center, multi-dose trial designed to estimate the maximum tolerated dose (MTD) and select the recommended dose for phase 2 (RP2D) investigations of PF- 05082566 in combination with KW-0761 (mogamulizumab) in patients with advanced solid tumors. Once the MTD of PF-05082566 administered in combination with KW-0761 is estimated (dose finding), one or more expansion cohorts of patients with selected advanced solid tumors (dose-expansion ) will be enrolled to further characterize the combination in term of safety profile, anti tumor activity, pharmacokinetics, pharmacodynamics and biomarkers modulation.

Condition or disease Intervention/treatment Phase
Advanced/Metastatic Solid Tumors Drug: PF-05082566 Drug: KW-0761 Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Study Of Pf-05082566 In Combination With Mogamulizumab (Kw-0761) In Patients With Advanced Solid Tumors
Actual Study Start Date : May 26, 2015
Actual Primary Completion Date : September 26, 2017
Actual Study Completion Date : October 10, 2017

Arm Intervention/treatment
Experimental: PF-05082566 + KW-0761
During Parts 1 & 2 Mogamulizumab and PF-05082566 will be administered at appropriate intervals. Part 1: PF-05082566 dose escalation; increased doses of PF-05082566 IV are administered with mogamulizumab IV. Part 2: patients will be treated with the maximum tolerated dose established in Phase 1 for the combination.
Drug: PF-05082566
Part 1: PF-05082566 dose escalation; Increased doses of PF-05082566 IV are administered at appropriate intervals. Part 2: MTD of PF-05082566 IV established in Part 1 is administered.
Drug: KW-0761
Part 1: KW-0761 IV administered at appropriate intervals. Part 2: KW-0761 IV administered at appropriate intervals at the MTD dose for the combination.
Other Name: KW-0761= Mogamulizumab or POTELIGEO®



Primary Outcome Measures :
  1. Number of participant with Dose-Limiting Toxicities (DLTs) [ Time Frame: First 2 cycles of treatment ]
    DLTs of PF-05082566 in combination with KW-0761 occurred during the first 2 treatment cycles


Secondary Outcome Measures :
  1. Maximum serum concentration (Cmax) of PF-05082566 [ Time Frame: Cycles 1 - 5 up to 5 months ]
    Cmax is defined as the maximum serum concentration of PF-05082566

  2. Maximum serum concentration (Cmax) of KW-0761 [ Time Frame: Cycles 1 & 5, up to 5 months ]
    Cmax is defined as the maximum serum concentration of KW-0761

  3. Time to reach the maximum serum concentration (Tmax) of PF-05082566 [ Time Frame: Cycles 1 - 5, up to 5 months ]
    Tmax is the time needed from the start of infusion, to reach the maximum serum concentration of PF-05082566

  4. Time to reach the maximum serum concentration (Tmax) of KW-0761 [ Time Frame: Cycles 1 & 5, up to 5 months ]
    Tmax is the time needed from the start of infusion, to reach the maximum serum concentration of KW-0761

  5. Trough serum concentration (Ctrough) of PF-05082566 [ Time Frame: Cycles 1 - 5, 8, 12, 16, 20, 24 up to 24 months ]
    Ctrough is defined as the concentration at the end of PF-05082566 dosage interval

  6. Trough serum concentration (Ctrough) of KW-0761 [ Time Frame: Cycles 1 - 5, 8, 12, 16, 20, 24 up to 24 months ]
    Ctrough is defined as the concentration at the end of KW-0761 dosage interval

  7. Area Under the Curve0-last (AUC0-last) of PF-05082566 [ Time Frame: Cycle 5 up to 5 months ]
    AUC0-last is the area under the curve from time 0 to last measurable concentration of PF-05082566

  8. Area Under the Curve0-last (AUC0-last) of KW-0761 [ Time Frame: Cycle 5 up to 5 months ]
    AUC0-last is the area under the curve from time 0 to last measurable concentration of KW-0761

  9. Area Under the Curve 0-tau (AUC0-tau) of PF-05082566 [ Time Frame: Cycle 5, up to 5 months ]
    AUC0-tau is the area under the concentration curve over the dosing interval of PF-05082566

  10. Area Under the Curve0-tau (AUC0-tau) of KW-0761 [ Time Frame: Cycle 5, up to 5 months ]
    AUC0-tau is the area under the concentration curve over the dosing interval of KW-0761

  11. Elimination half life (t½) of PF-05082566 [ Time Frame: Cycle 5, up to 5 months ]
    t1/2 is defined as the time required for the concentration of PF-05082566 to reach half of its original value.

  12. Elimination half life (t½) of KW-0761 [ Time Frame: Cycle 5 up to 5 months ]
    t1/2 is defined as the time required for the concentration of KW-0761 to reach half of its original value.

  13. Volume of distribution at a steady state (Vss) of PF-05082566 [ Time Frame: Cycle 5, up to 5 months ]
    Vss is defined as the actual blood and tissue volume into which PF-05082566 is distribute and the relative binding of drug to protein in this spaces.

  14. Volume of distribution at a steady state (Vss) of KW-0761 [ Time Frame: Cycle 5, up to 5 months ]
    Vss is defined as the actual blood and tissue volume into which KW-0761 is distribute and the relative binding of drug to protein in this spaces.

  15. Clearance (CL) of PF-05082566 [ Time Frame: Cycle 5, up to 5 months ]
    Clearance (CL) is defined as the volume of blood from which PF-05082566 can be completely removed per unit of time

  16. Clearance (CL) of KW-0761 [ Time Frame: Cycle 5, up to 5 months ]
    Clearance (CL) is defined as the volume of blood from which KW-0761 can be completely removed per unit of time

  17. Anti-Drug Antibody (ADA) levels of PF-05082566/Neutralizing antibodies (Nab) titers for PF-05082566 [ Time Frame: Cycles 1, 3, 5, 8, 12, 16, 20, 24 up to 24 months ]
    Immunogenicity assessments of PF-05082566

  18. Anti-Drug Antibody (ADA) levels of KW-0761/Neutralizing antibodies (Nab) titers for KW-0761 [ Time Frame: Cycles 1, 3, 5, 8, 12, 16, 20, 24 up to 24 months ]
    Immunogenicity assessments of KW-0761

  19. Number of participants with Objective Response [ Time Frame: Every 8 weeks up to 24 months ]
    Number of participants with objective response (ie, confirmed complete or partial response according to RECIST version 1.1 and Immune Related Response Criteria (irRECIST))

  20. Duration of Response (DR) [ Time Frame: Every 8 weeks from the first occurrence of CR or PR, until disease progression or death up to 24 months ]
    For participants in the expansion cohorts, who achieved on treatment a complete (CR) or partial (PR) response as per RECIST version 1.1 and irRECIST. DR is the time in days between the first date of documentation of CR or PR and the date of tumor progression or death due to any cause, whichever occurred first

  21. Time to Response (TTR) [ Time Frame: Every 8 weeks up to 24 months ]
    For participant to the expansion cohort only. TTR is defined as time from the date of the first dose of study treatment to the date of the first documented objective response by RECIST version 1.1 and irRECIST

  22. Progression Free Survival (PFS) [ Time Frame: Every 8 weeks up to 24 months ]
    For participants to the expansion cohorts only. PFS is defined as the difference in days between the first date that criteria for progression (by RECIST v 1.1 and irRECIST) was met or the patient died due to any cause and the date of registration



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

Inclusion Criteria:

  • Histological or cytological diagnosis of advanced/metastatic solid tumor malignancy. Dose Finding Cohorts: Tumor types will be limited to CRC, SCCHN, squamous NSCLC, bladder, or ovarian carcinomas which have progressed on standard therapy, or for which no standard therapy is available.
  • Measurable disease by RECIST version 1.1.
  • For Expansion Cohorts only: patients must have tumor accessible for biopsies (core needle biopsy or excision preferred).
  • Age 18 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Adequate bone marrow, renal and liver function.
  • Serum/urine pregnancy test (for females of childbearing potential) negative at screening and before the patient will receive the study treatment.
  • Male and female patients of childbearing potential and at risk for pregnancy must agree to use two (2) highly effective methods of contraception throughout the study and for 60 days after the last dose of assigned study treatment.

Exclusion Criteria:

  • Active central nervous system primary or secondary malignancies, active seizure disorder, spinal cord compression, or carcinomatous meningitis.
  • Therapeutic or experimental monoclonal antibodies in last 60 days prior registration.
  • Systemic anticancer therapy or major surgery within 28 days prior to registration. In absence of toxicity from prior systemic anticancer therapy, 5 half-lives since completion of prior systemic anticancer therapy is allowed.
  • Systemic steroids, any other form of immunosuppressive therapy or radiation therapy within 14 days prior to registration.
  • Live vaccine within 30 days prior to registration.
  • Severe hypersensitivity reaction to treatment with another monoclonal antibody, known or suspected hypersensitivity to study drugs or any component of their formulation.
  • History of autoimmune disease or known inflammatory bowel disease.
  • Uncontrolled hypertension (blood pressure >150/100 mmHg despite optimal medical therapy) or any of the following within 12 months prior to registration: myocardial infarction, congenital long QT syndrome, torsade de points, arrhythmias, right bundle branch block and left anterior hemiblock uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, ongoing NCICTCAE Grade 2 cardiac dysrhythmias, atrial fibrillation or QTcF interval >470 msec.

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): NCT02444793


Locations
United States, California
UC San Diego Moores Cancer Center
La Jolla, California, United States, 92037-0845
UC San Diego Medical Center - La Jolla(Thornton Hospital)
La Jolla, California, United States, 92037
University Of California / San Diego Moores Cancer Center
La Jolla, California, United States, 92093
University of California San Diego Moores Cancer Center
La Jolla, California, United States, 92093
UC San Diego Medical Center - Hillcrest
San Diego, California, United States, 92103
United States, District of Columbia
Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
Georgetown University
Washington, District of Columbia, United States, 20007
Medstar Georgetown University Hospital
Washington, District of Columbia, United States, 20007
United States, Florida
Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
United States, Michigan
Henry Ford Hospital Research Pharmacy
Detroit, Michigan, United States, 48202
Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, North Carolina
UNC Cancer Hospital Infusion Pharmacy
Chapel Hill, North Carolina, United States, 27514
UNC Hospitals, University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7600
United States, Ohio
Cleveland Clinic Taussig Cancer Institute
Cleveland, Ohio, United States, 44195
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, South Dakota
Sanford Cancer Center
Sioux Falls, South Dakota, United States, 57104
Sanford Research
Sioux Falls, South Dakota, United States, 57104
Sanford USD Medical Center
Sioux Falls, South Dakota, United States, 57105
United States, Tennessee
Tennessee Oncology, PLLC
Gallatin, Tennessee, United States, 37066
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37203
The Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Pfizer
Kyowa Hakko Kirin Co., Ltd
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
Principal Investigator: Michael J Pishvaian, MD, PhD Georgetown University
Principal Investigator: Esra E Cohen, MD University of California, San Diego
Principal Investigator: Dale R Shepard, MD, PhD The Cleveland Clinic

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02444793     History of Changes
Other Study ID Numbers: B1641004
First Posted: May 14, 2015    Key Record Dates
Last Update Posted: April 25, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Information relating to our policy on data sharing and the process for requesting data can be found at the following link: http://www.pfizer.com/research/clinical_trials/trial_data_and_results/data_requests

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