Clinical trial NCT02444793: A Study of PF-05082566 In Combination With Mogamulizumab In Patients With Advanced Solid Tumors
Official title: A PHASE 1B STUDY OF PF-05082566 IN COMBINATION WITH MOGAMULIZUMAB (KW-0761) IN PATIENTS WITH ADVANCED SOLID TUMORS
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced/Metastatic Solid Tumors
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Kyowa Kirin Co., Ltd.
First posted: 2015-05-14
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLT)
timeFrame: First 2 Cycles (28 days in each cycle)
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (All Causalities)
timeFrame: Day 1 up to 60 days after last dose of study treatment
measure: Number of Participants With Treatment-Emergent Adverse Events (PF-05082566 Related)
timeFrame: Day 1 up to 60 days after last dose of study treatment
measure: Number of Participants With Treatment-Emergent Adverse Events (Mogamulizumab Related)
timeFrame: Day 1 up tp 60 days after last dose of study treatment
measure: Number of Participants With Hematology Laboratory Abnormalities as Characterized by Type, Frequency, Severity (as Graded by NCI CTCAE) -Grades 3 or 4
timeFrame: Screening (within 28 days prior to registration) up to 28 days (+7 days) after the last dose of study treatment
measure: Number of Participants With Chemistries Laboratory Abnormalities as Characterized by Type, Frequency, Severity (as Graded by NCI CTCAE) -Grades 3 or 4
timeFrame: Screening (within 28 days prior to registration) up to 28 days (+7 days) after the last dose of study treatment
measure: Number of Participants With Clinical Significant Observations in Vital Signs
timeFrame: Screening (within 28 days prior to registration) up to 28 days (+7 days) after the last dose of study treatment
measure: Number of Participants With Significant Changes From Baseline in Physical Examination
timeFrame: Cycle 2 Day 1; End of the treatment.
measure: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Shift to Grades 2, 3, 4 or 5
timeFrame: Screening (within 28 days prior to registration) up to 28 days (+7 days) after the last dose of study treatment
measure: Maximum Observed Serum Concentration (Cmax) of PF-05082566-Cycle 5
timeFrame: Cycle 5: Day 1 at pre-dose, at the end of PF-05082566 infusion, and at 2, 6, 168 hours (Day 8) and 336 hours (Day 15) after the start of PF-05082566 infusion.
measure: Dose Normalized Cmax of PF-05082566-Cycle 5
timeFrame: Cycle 5: Day 1 at pre-dose, at the end of PF-05082566 infusion, and at 2, 6, 168 hours (Day 8) and 336 hours (Day 15) after the start of PF-05082566 infusion.
measure: Cmax of Mogamulizumab-Cycles 1 and 5
timeFrame: Cycle 1: pre-dose and at the end of mogamulizumab infusion on Days 1, 8, 15 and 22; Cycle 5: Pre-dose, at the end of mogamulizumab infusion, and at 6 hours, 168 hours (Day 8) after the start of the mogamulizumab infusion; Pre-dose on Day 15
measure: Pre-dose Concentration During Multiple Dosing (Ctrough) of PF-05082566-Cycle 5
timeFrame: Cycle 5: Day 1 at pre-dose, at the end of PF-05082566 infusion, and at 2, 6, 168 hours (Day 8) and 336 hours (Day 15) after the start of PF-05082566 infusion.
measure: Ctrough of Mogamulizumab- Cycle 5
timeFrame: Cycle 5: Pre-dose, at the end of mogamulizumab infusion, and at 6 hours, 168 hours (Day 8) after the start of the mogamulizumab infusion; Pre-dose on Day 15
measure: Time for Cmax (Tmax) of PF-05082566-Cycle 5
timeFrame: Cycle 5: Day 1 at pre-dose, at the end of PF-05082566 infusion, and at 2, 6, 168 hours (Day 8) and 336 hours (Day 15) after the start of PF-05082566 infusion.
measure: Time of Last Measurable Concentration (Tlast) of PF-05082566-Cycle 5
timeFrame: Cycle 5: Day 1 at pre-dose, at the end of PF-05082566 infusion, and at 2, 6, 168 hours (Day 8) and 336 hours (Day 15) after the start of PF-05082566 infusion.
measure: Tmax of Mogamulizumab-Cycles 1 and 5
timeFrame: Cycle 1: pre-dose and at the end of mogamulizumab infusion on Days 1, 8, 15 and 22; Cycle 5: Pre-dose, at the end of mogamulizumab infusion, and at 6 hours, 168 hours (Day 8) after the start of the mogamulizumab infusion; Pre-dose on Day 15
measure: Tlast of Mogamulizumab-Cycles 1 and 5
timeFrame: Cycle 1: pre-dose and at the end of mogamulizumab infusion on Days 1, 8, 15 and 22; Cycle 5: Pre-dose, at the end of mogamulizumab infusion, and at 6 hours, 168 hours (Day 8) after the start of the mogamulizumab infusion; Pre-dose on Day 15
measure: Area Under the Serum Concentration-time Profile From Time 0 to the Time of the Last Measurable Concentration (AUClast) of PF-05082566-Cycle 5
timeFrame: Cycle 5: Day 1 at pre-dose, at the end of PF-05082566 infusion, and at 2, 6, 168 hours (Day 8) and 336 hours (Day 15) after the start of PF-05082566 infusion.
measure: Dose Normalized AUClast of PF-05082566-Cycle 5
timeFrame: Cycle 5: Day 1 at pre-dose, at the end of PF-05082566 infusion, and at 2, 6, 168 hours (Day 8) and 336 hours (Day 15) after the start of PF-05082566 infusion.
measure: AUClast of Mogamulizumab-Cycles 1 and 5
timeFrame: Cycle 1: pre-dose and at the end of mogamulizumab infusion on Days 1, 8, 15 and 22; Cycle 5: Pre-dose, at the end of mogamulizumab infusion, and at 6 hours, 168 hours (Day 8) after the start of the mogamulizumab infusion; Pre-dose on Day 15
measure: Area Under the Serum Concentration-time Profile From Time 0 to 168 Hours (AUC168) of Mogamulizumab-Cycle 1
timeFrame: Cycle 1: pre-dose and at the end of mogamulizumab infusion on Days 1, 8, 15 and 22
measure: Area Under the Serum Concentration-time Profile From Time 0 to Time Tau (AUCtau) of Mogamulizumab-Cycle 5
timeFrame: Cycle 5: Pre-dose, at the end of mogamulizumab infusion, and at 6 hours, 168 hours (Day 8) after the start of the mogamulizumab infusion; Pre-dose on Day 15
measure: Clearance (CL) of Mogamulizumab-Cycle 5
timeFrame: Cycle 5: Pre-dose, at the end of mogamulizumab infusion, and at 6 hours, 168 hours (Day 8) after the start of the mogamulizumab infusion; Pre-dose on Day 15
measure: Anti-Drug Antibody (ADA) Titer for PF-05082566
timeFrame: Pre-dose on Day 1 of Cycles 1, 3, 5, 8, 12, 16, 20, 24 up to 24 months
measure: Neutralizing Antibodies (NAb) Titers for PF-05082566
timeFrame: Pre-dose on Day 1 of Cycles 1, 3, 5, 8, 12, 16, 20, 24 up to 24 months
measure: Anti-Drug Antibody (ADA) Titers for Mogamulizumab
timeFrame: Pre-dose on Day 1 of Cycles 1, 3, 5, 8, 12, 16, 20, 24 up to 24 months
measure: Neutralizing Antibodies (NAb) Titers for Mogamulizumab
timeFrame: Pre-dose on Day 1 of Cycles 1, 3, 5, 8, 12, 16, 20, 24 up to 24 months
measure: Number of Participants With Objective Response (OR) and Immune-related Objective Response (irOR)
timeFrame: Every 8 weeks up to 24 months
measure: Time to Response (TTR) and Immue-related Time to Response (irTTR)-Dose Expansion Portion
timeFrame: Every 8 weeks up to 24 months
measure: Duration of Response (DR) and Immune-related DR (irDR) -Dose Expansion Portion
timeFrame: Every 8 weeks from the first occurrence of CR or PR, until disease progression or death up to 24 months
measure: Progression Free Survival (PFS) and Immune-related PFS (irPFS) - Dose Expansion Portion
timeFrame: Every 8 weeks up to 24 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: La Jolla
country: United States
facility: UC San Diego Medical Center - La Jolla(Thornton Hospital)
state: California
city: La Jolla
country: United States
facility: University Of California / San Diego Moores Cancer Center
state: California
city: La Jolla
country: United States
facility: University of California San Diego Moores Cancer Center
state: California
city: San Diego
country: United States
facility: UC San Diego Medical Center - Hillcrest
state: California
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Washington
country: United States
facility: Medstar Georgetown University Hospital
state: District of Columbia
city: Tampa
country: United States
facility: Moffitt Cancer Center and Research Institute
state: Florida
city: Detroit
country: United States
facility: Henry Ford Hospital Research Pharmacy
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Chapel Hill
country: United States
facility: UNC Cancer Hospital Infusion Pharmacy
state: North Carolina
city: Chapel Hill
country: United States
facility: UNC Hospitals, University of North Carolina at Chapel Hill
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Sioux Falls
country: United States
facility: Sanford Cancer Center
state: South Dakota
city: Sioux Falls
country: United States
facility: Sanford Research
state: South Dakota
city: Sioux Falls
country: United States
facility: Sanford USD Medical Center
state: South Dakota
city: Gallatin
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: The Sarah Cannon Research Institute
state: Tennessee
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
affiliation: Georgetown University
name: Michael J Pishvaian, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Diego
name: Esra E Cohen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Cleveland Clinic
name: Dale R Shepard, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cohen EEW, Pishvaian MJ, Shepard DR, Wang D, Weiss J, Johnson ML, Chung CH, Chen Y, Huang B, Davis CB, Toffalorio F, Thall A, Powell SF. A phase Ib study of utomilumab (PF-05082566) in combination with mogamulizumab in patients with advanced solid tumors. J Immunother Cancer. 2019 Dec 4;7(1):342. doi: 10.1186/s40425-019-0815-6.