A Study Of PF-05082566 As A Single Agent And In Combination With Rituximab
4. mars 2020 oppdatert av: Pfizer
A PHASE 1 STUDY OF PF-05082566 AS A SINGLE AGENT IN PATIENTS WITH ADVANCED CANCER, AND IN COMBINATION WITH RITUXIMAB IN PATIENTS WITH NON-HODGKIN'S LYMPHOMA (NHL)
A study of PF-05082566, a 4-1BB agonist monoclonal antibody (mAb), in patients with solid tumors or b-cell lymphomas, and in combination with rituximab in patients with CD20 positive Non-Hodgkin's Lymphoma (NHL).
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Faktiske)
190
Fase
- Fase 1
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Victoria
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Melbourne, Victoria, Australia, 3000
- Peter MacCallum Cancer Centre
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California
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Duarte, California, Forente stater, 91010
- City of Hope
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La Jolla, California, Forente stater, 92093
- UC San Diego Moores Cancer Center
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La Jolla, California, Forente stater, 92037-0845
- UC San Diego Moores Cancer Center-Investigational Drug Services
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La Jolla, California, Forente stater, 92037
- UC San Diego Medical Center-La Jolla (Jacobs Medical Center/Thornton Hospital)
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Los Angeles, California, Forente stater, 90095
- Ronald Reagan UCLA Medical Center, Drug Information Center
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Los Angeles, California, Forente stater, 90095
- UCLA Hematology-Oncology Clinic
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Los Angeles, California, Forente stater, 90095
- Research Administration Office: Clinical Research Unit
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Los Angeles, California, Forente stater, 90095
- UCLA Bowyer Clinic
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Palo Alto, California, Forente stater, 94304
- Stanford University Medical Center
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Palo Alto, California, Forente stater, 94305
- Stanford University Medical Center
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San Diego, California, Forente stater, 92103
- UC San Diego Medical Center - Hillcrest
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Santa Monica, California, Forente stater, 90404
- Santa Monica UCLA Hematology & Oncology Clinic
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Stanford, California, Forente stater, 94305
- Stanford University Medical Center
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District of Columbia
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Washington, District of Columbia, Forente stater, 20007
- MedStar Georgetown University Hospital
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Washington, District of Columbia, Forente stater, 20007
- Georgetown University Medical Center Department of Pharmacy, Research
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Georgia
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Atlanta, Georgia, Forente stater, 30322
- Emory University Hospital
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Atlanta, Georgia, Forente stater, 30308
- Emory University Hospital Midtown
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Atlanta, Georgia, Forente stater, 30322
- The Emory Clinic
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Atlanta, Georgia, Forente stater, 30322
- Winship Cancer Institute
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Atlanta, Georgia, Forente stater, 30322
- The Emory Clinic, Building A
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Massachusetts
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Boston, Massachusetts, Forente stater, 02215
- Dana-Farber Cancer Institute
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Boston, Massachusetts, Forente stater, 02115
- Brigham and Woman's Hospital
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Michigan
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Ann Arbor, Michigan, Forente stater, 48109
- University of Michigan Health System
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Missouri
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Creve Coeur, Missouri, Forente stater, 63141
- Siteman Cancer Center-West County
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Saint Louis, Missouri, Forente stater, 63110
- Washington University School of Medicine
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Saint Louis, Missouri, Forente stater, 63110
- Barnes-Jewish Hospital
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Saint Louis, Missouri, Forente stater, 63110
- Washington University Infusion Center Pharmacy
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Saint Louis, Missouri, Forente stater, 63110-1094
- Barnes-Jewish Hospital
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Saint Louis, Missouri, Forente stater, 63129
- Siteman Cancer Center- South County
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Saint Peters, Missouri, Forente stater, 63376
- Siteman Cancer Center - St. Peters
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New York
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New York, New York, Forente stater, 10065
- Memorial Sloan Kettering Cancer Center
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Texas
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Houston, Texas, Forente stater, 77030
- The University of Texas - M.D. Anderson Cancer Center
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San Antonio, Texas, Forente stater, 78229
- South Texas Accelerated Research Therapeutics, LLC
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Washington
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Seattle, Washington, Forente stater, 98109
- Seattle Cancer Care Alliance
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Seattle, Washington, Forente stater, 98195
- University of Washington Medical Center
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RENNES cedex 9, Frankrike, 35033
- Centre d'investigation Clinique
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BO
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Bologna, BO, Italia, 40138
- Az. Ospedaliera-Univer. di Bologna Policlinico S. Orsola Malpighi
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MI
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Milano, MI, Italia, 20132
- Ospedale San Raffaele di Milano
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Akita, Japan, 010-8543
- Akita University Hospital
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Tokyo, Japan, 135-8550
- The Cancer Institute Hospital of Japanese Foundation for Cancer Research
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Chiba
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Kashiwa, Chiba, Japan, 277-8577
- National Cancer Center Hospital East
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år og eldre (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
Inclusion Criteria
- Portion A: Histological or cytological diagnosis of advanced/metastatic solid tumor malignancy or B cell lymphoma, for which no curative therapy is available. Portion A expansion includes patients who have documented disease progression on a checkpoint inhibitor (anti CTLA 4, anti PD1/PD L1 antibodies) per RECIST criteria. Tumor types include metastatic melanoma, renal cell carcinoma (RCC), non-small cell lung cancer (NCSLC) and squamous cell carcinoma of the head and neck (SCCHN). Patients in the dose expansion stage are required to provide archival or baseline (obtained during the screening period) tumor biopsies.
- Portion B: Histological confirmed relapsed or refractory CD20 positive NHL for which no curative therapy is available. Patients enrolled in the expansion cohort must have archival tissue available, sampled within 6 months of study entry. The Expansion cohort includes patients with FL or DLBCL with relapsed or refractory disease.
- Measurable disease with at least one extranodal tumor mass >1.0 cm in the greatest transverse diameter (GTD) or in the case of malignant lymph nodes >1.5 cm in the GTD.
- ECOG performance status of ≤ 1.
- Adequate bone marrow function, for Portion A: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count ≥100 x 109/L, hemoglobin >9.0 g/dL. For Portion B: ANC ≥ 1.0 x 109/L, platelet count ≥ 75 x 109/L, and hemoglobin ≥ 8.0 g/dL. In both cases, patients must be transfusion independent at least 14 days prior to screening.
- Serum creatinine ≤ 2 x ULN or estimated creatinine clearance ≥ 50 ml/min.
- Total serum bilirubin ≤ 1.5 x ULN unless the patient has documented Gilbert syndrome and AST and ALT ≤ 2.5 x ULN.
Exclusion Criteria
- Patients with known symptomatic brain metastases requiring steroids.
- Prior allogeneic hematopoietic stem cell transplant.
- Immunosuppressive regimens involving systemic corticosteroids within 14 days before the first dose of study treatment.
- Therapeutic or experimental monoclonal antibodies within 28 day or prior radiation therapy within 14 days of the first dose of study drug.
- Autoimmune disorders and other diseases that compromise or impair the immune system.
- Unstable or serious concurrent medical conditions in the previous 6 months.
- Prior therapy with any anti CD137 monoclonal antibody.
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: Portion A
PF-05082566 single agent in patients with advanced cancer
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Intravenous, Dose escalation, once per month
IV, Dose escalation, once per month
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Eksperimentell: Portion B
PF-05082566 in combination with rituximab in patients with Non-Hodgkin's Lymphoma
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Intravenous, Dose escalation, once per month
IV, Dose escalation, once per month
Intravenous, 375 mg/m2, once per week for 4 weeks
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Number of Participants With Dose-Limiting Toxicities (DLTs) in First 2 Cycles of Portion A
Tidsramme: Cycle 1 Day 1 to Cycle 2 Day 29 in Portion A (up to 57 days, each cycle = 28 days)
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DLT: Any of the following adverse events (AEs) occurred in the first 2 cycles of treatment (up to 28 days post second dose) which was attributed to PF-05082566 alone for Portion A and not related to progressive disease.
Hematologic: Grade 4 neutropenia lasting more than (>)7 days; febrile neutropenia; neutropenic infection; Grade ≥3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia; Grade ≥3 hemolysis.
Non-Hematologic: Grade ≥3 toxicities, except those Grade 3 events that responded to treatment (eg, Grade 3 nausea, vomiting, diarrhea responding to standard medical supportive care within 48 hours would not be considered a DLT).
Severity of AEs were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE).
Each cycle=28 days.
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Cycle 1 Day 1 to Cycle 2 Day 29 in Portion A (up to 57 days, each cycle = 28 days)
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Number of Participants With DLTs in First 2 Cycles of Portion B
Tidsramme: Cycle 1 Day 1 to Cycle 2 Day 29 in Portion B (up to 57 days, each cycle = 28 days)
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DLT: Any of the following AEs occurred in the first 2 cycles of treatment (up to 28 days post second dose) which was attributed to PF-05082566 in combination with rituximab for Portion B and not related to progressive disease.
Hematologic: Grade 4 neutropenia lasting more than (>)7 days; febrile neutropenia; neutropenic infection; Grade ≥3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia; Grade ≥3 hemolysis.
Non-Hematologic: Grade ≥3 toxicities, except those Grade 3 events that responded to treatment (eg, Grade 3 nausea, vomiting, diarrhea responding to standard medical supportive care within 48 hours would not be considered a DLT).
Severity of AEs were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE).
Each cycle=28 days.
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Cycle 1 Day 1 to Cycle 2 Day 29 in Portion B (up to 57 days, each cycle = 28 days)
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) in Portion A
Tidsramme: Up to approximately 2 years
|
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of dying); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect.
AEs included both non-serious AEs and SAEs.
Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment.
Causality of AEs was determined by the investigator.
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Up to approximately 2 years
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Number of Participants With Treatment-Emergent AEs by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade in Portion A
Tidsramme: Up to approximately 2 years
|
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment.
Severity of AEs were graded according to NCI CTCAE version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE).
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Up to approximately 2 years
|
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Number of Participants With Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion A
Tidsramme: Up to approximately 2 years
|
Following hematology laboratory abnormalities were graded per NCI CTCAE version 4.03: anemia, hemoglobin increased, lymphocyte count increased, lymphopenia, neutrophils (absolute), platelets, white blood cells.
The abnormalities with at least 1 participant are presented here.
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Up to approximately 2 years
|
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Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion A
Tidsramme: Up to approximately 2 years
|
Following chemistries laboratory abnormalities were graded per NCI CTCAE version 4.03: alanine aminotransferase (ALT), Alkaline phosphatase, Aspartate aminotransferase (AST), bilirubin (total), creatinine, gamma glutamyl transferase (GGT), hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia.
The abnormalities with at least 1 participant are presented here.
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Up to approximately 2 years
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Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion A
Tidsramme: Up to approximately 2 years
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For vital signs in Portion A, blood pressure and pulse rate were measured.
Clinical significance was determined by the investigator.
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Up to approximately 2 years
|
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PF-05082566 Maximum Observed Serum Concentration (Cmax) in Portion A
Tidsramme: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose
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Cmax of PF-05082566 was observed directly from data.
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Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose
|
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PF-05082566 Pre-dose Trough Concentration During Multiple Dosing (Ctrough) in Portion A
Tidsramme: Day 1 pre-dose of Cycle 2
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Ctrough of PF-05082566 was observed directly from data.
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Day 1 pre-dose of Cycle 2
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PF-05082566 Time for Maximum Observed Serum Concentration (Tmax) in Portion A
Tidsramme: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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Tmax of PF-05082566 was observed directly from data as time of Cmax.
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Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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PF-05082566 Area Under the Serum Concentration-Time Profile (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUClast) in Portion A
Tidsramme: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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AUClast of PF-05082566 was determined by linear/log trapezoidal method.
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Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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PF-05082566 AUC From Time 0 to Infinity (AUCinf) in Portion A
Tidsramme: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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AUCinf = AUClast + (Clast*/kel), where Clast* is the estimated concentration at the time of the last measurable concentration and kel is the terminal phase rate constant calculated as the absolute value of the slope of a linear regression during the terminal phase of the natural log-transformed concentration time profile.
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Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
|
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PF-05082566 AUC From Time 0 to Time of Dosing Interval (AUCtau) in Portion A
Tidsramme: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
|
AUCtau of PF-05082566 was determined using linear/log trapezoidal method.
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Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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PF-05082566 Clearance (CL) in Portion A
Tidsramme: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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CL = Dose/AUCinf for Cycle 1 and Dose/AUCtau for Cycle 2. It was reported in units of milliliter per hour per kilogram (mL/hr/kg).
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Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
|
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PF-05082566 Volume of Distribution at Steady State (Vss) in Portion A
Tidsramme: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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Vss = CL × MRT, where CL is clearance and MRT is the mean residence time after intravenous administration.
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Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
|
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Number of Participants With Positive Anti-Drug Antibody (ADA) for PF-05082566 in Portion A
Tidsramme: Up to approximately 2 years
|
ADA for PF-05082566 was detected using electrochemiluminescence assay.
Positive ADA for PF-05082566: titer>=6.23.
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Up to approximately 2 years
|
|
Number of Participants With QTc Interval Meeting Categorical Summarization Criteria in Portion A
Tidsramme: Up to approximately 2 years
|
Categorical summarization criteria for QTc interval (time from ECG Q wave to the end of the T wave corresponding to electrical systole corrected for heart rate): 1) absolute value of >450 to <=480 milliseconds (msec), >480 to <=500 msec, >500 msec; 2) a maximum change from baseline of >30 to <=60 msec or >60 msec.
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Up to approximately 2 years
|
|
Percentage of Participants Achieving Objective Response Per Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 in Portion A
Tidsramme: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
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Objective response: confirmed best overall response (BOR) of complete response (CR) or partial response (PR) per RECIST version 1.1.
BOR of CR: target lesions and non-target diseases achieved CR, without new lesions.
BOR of PR: target lesions achieved CR or PR while non-target diseases were non-CR/non-progression of disease (non-PD), indeterminate or missing, and without new lesions.
For target lesions, CR: complete disappearance of all target lesions except nodal disease (target nodes must decrease to normal size); PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions.
For non-target diseases, CR: disappearance of all non-target lesions and normalization of tumor marker levels; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits; Indeterminate: progression had not been determined and >=1 non-target sites were not assessed or assessment methods were inconsistent with those used at baseline.
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Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
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Duration of Response in Portion A
Tidsramme: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
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Duration of response: the time from first documentation of objective response (confirmed BOR of CR or PR per RECIST version 1.1) to the date of first documentation of objective progression of disease (PD) or death due to any cause.
Objective PD per RECIST version 1.1: >=20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 millimeters (mm); or unequivocal progression of pre-existing lesions for non-target disease; or appearance of new lesions.
This outcome measure reports the individual values for evaluable participants (instead of medians etc) due to the limited number of events.
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Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
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Time to Response in Portion A
Tidsramme: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
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Time to response: the time from Cycle 1 Day 1 to the first documentation of objective response (confirmed BOR of CR or PR per RECIST version 1.1).
BOR of CR: target lesions and non-target diseases achieved CR, without new lesions.
BOR of PR: target lesions achieved CR or PR while non-target diseases were non-CR/non-PD, indeterminate or missing, and without new lesions.
For target lesions, CR: complete disappearance of all target lesions except nodal disease (target nodes decreased to normal size); PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions.
For non-target diseases, CR: disappearance of all non-target lesions and normalization of tumor marker levels; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits; Indeterminate: progression had not been determined and >=1 non-target sites were not assessed or assessment methods were inconsistent with those used at baseline.
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Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
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Progression-Free Survival in Portion A
Tidsramme: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Progression-free survival: the time from Cycle 1 Day 1 to the date of the first documentation of objective PD or death due to any cause, whichever occurred first.
Objective PD per RECIST version 1.1: >=20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm; or unequivocal progression of pre-existing lesions for non-target disease; or appearance of new lesions.
|
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
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Overall Survival in Portion A
Tidsramme: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Overall survival was defined as the time from Cycle 1 Day 1 to the date of death due to any cause.
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Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
|
Number of Participants With Treatment-Emergent AEs and SAEs in Portion B
Tidsramme: Up to approximately 4 years
|
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of dying); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect.
AEs included both non-serious AEs and SAEs.
Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment.
Causality of AEs was determined by the investigator.
|
Up to approximately 4 years
|
|
Number of Participants With Treatment-Emergent AEs by Maximum NCI CTCAE Grade in Portion B
Tidsramme: Up to approximately 4 years
|
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment.
Severity of AEs were graded according to NCI CTCAE version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE).
|
Up to approximately 4 years
|
|
Number of Participants With Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion B
Tidsramme: Up to approximately 2 years
|
Following hematology laboratory abnormalities were graded per NCI CTCAE version 4.03: anemia, hemoglobin increased, lymphocyte count increased, lymphopenia, neutrophils (absolute), platelets, white blood cells.
The abnormalities with at least 1 participant are presented here.
|
Up to approximately 2 years
|
|
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion B
Tidsramme: Up to approximately 2 years
|
Following chemistries laboratory abnormalities were graded per NCI CTCAE version 4.03: alanine aminotransferase (ALT), Alkaline phosphatase, Aspartate aminotransferase (AST), bilirubin (total), creatinine, gamma glutamyl transferase (GGT), hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia.
The abnormalities with at least 1 participant are presented here.
|
Up to approximately 2 years
|
|
Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion B
Tidsramme: Up to approximately 2 years
|
For vital signs in Portion B, blood pressure, pulse rate, and body temperature were measured.
Clinical significance was determined by the investigator.
|
Up to approximately 2 years
|
|
PF-05082566 Cmax in Portion B
Tidsramme: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
Cmax of PF-05082566 was observed directly from data.
|
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
|
PF-05082566 Ctrough in Portion B
Tidsramme: Day 1 pre-dose of Cycle 2
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Ctrough of PF-05082566 was observed directly from data.
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Day 1 pre-dose of Cycle 2
|
|
PF-05082566 Tmax in Portion B
Tidsramme: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
Tmax of PF-05082566 was observed directly from data as time of Cmax.
|
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
|
PF-05082566 AUClast in Portion B
Tidsramme: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
AUClast of PF-05082566 was determined by linear/log trapezoidal method.
|
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
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PF-05082566 AUCinf in Portion B
Tidsramme: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose.
|
AUCinf = AUClast + (Clast*/kel), where Clast* is the estimated concentration at the time of the last measurable concentration and kel is the terminal phase rate constant calculated as the absolute value of the slope of a linear regression during the terminal phase of the natural log-transformed concentration time profile.
|
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose.
|
|
PF-05082566 AUCtau in Portion B
Tidsramme: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
AUCtau of PF-05082566 was determined using linear/log trapezoidal method.
|
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
|
PF-05082566 CL in Portion B
Tidsramme: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
CL = Dose/AUCinf for Cycle 1 and Dose/AUCtau for Cycle 2.
|
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
|
PF-05082566 Vss in Portion B
Tidsramme: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
Vss = CL × MRT, where CL is clearance and MRT is the mean residence time after intravenous administration.
|
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
|
Rituximab Cmax and Ctrough in Portion B
Tidsramme: Day 1 pre-dose of Cycle 2
|
Cmax and Ctrough of rituximab were observed directly from data.
|
Day 1 pre-dose of Cycle 2
|
|
Number of Participants With Positive ADA for PF-05082566 and Rituximab in Portion B
Tidsramme: Up to approximately 2 years
|
ADA for PF-05082566 and rituximab was detected using electrochemiluminescence assay.
Positive ADA for PF-05082566: titer>=6.23.
Positive ADA for rituximab: titer>=1.88.
|
Up to approximately 2 years
|
|
Number of Participants With QTc Interval Meeting Categorical Summarization Criteria in Portion B
Tidsramme: Up to approximately 2 years
|
Categorical summarization criteria for QTc interval: 1) absolute value of >450 to <=480 milliseconds (msec), >480 to <=500 msec, >500 msec; 2) a maximum change from baseline of >30 to <=60 msec or >60 msec.
|
Up to approximately 2 years
|
|
Percentage of Participants Achieving Objective Response Per Cheson 2007 Criteria in Portion B
Tidsramme: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Objective Response in Portion B was defined as BOR of CR or PR according to Cheson 2007 criteria.
BOR of CR or PR per Cheson 2007: CR or PR of index lesions (complete disappearance of all detectable clinical and radiographic evidence of disease, all lymph nodes returned to normal size, spleen and/or liver if enlarged prior to therapy became normal or no longer palpable; or >=50% decrease in the sum of the product diameters [SPD] of up to 6 index lesions, no increase in size of other nodes, liver or spleen), without PD of non-index lesions (ie, without: new nonnodal lesion, new nodal lesion >=15 mm in greatest transverse diameter [GTD], unequivocal progression of existing non index lesions, bone marrow that was negative and is now positive, new circulating lymphoma cells in blood cell count and/or pleural fluid, new circulating blasts in the blood cell count), and without any new lesions.
|
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
|
Duration of Response in Portion B
Tidsramme: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Duration of Response in Portion B was defined, for participants with an objective response (BOR of CR or PR per Cheson 2007 criteria), as the time from first documentation of objective response to the date of first documentation of objective PD or death due to any cause.
Objective PD per Cheson 2007 was defined as: PD of index lesions (>=50% increase in SPD of previously involved sites from nadir), or PD of non-index lesions (new nonnodal lesion, new nodal lesion >=15 mm in GTD, unequivocal progression of existing non index lesions, bone marrow that was negative and is now positive, new circulating lymphoma cells in blood cell count and/or pleural fluid, new circulating blasts in the blood cell count), or appearance of new lesions.
|
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
|
Time to Response in Portion B
Tidsramme: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Time to response in Portion B was defined, for participants with an objective response (BOR of CR or PR per Cheson 2007 criteria), as the time from Cycle 1 Day 1 to the first documentation of objective response.
BOR of CR or PR per Cheson 2007: CR or PR of index lesions (complete disappearance of all detectable clinical and radiographic evidence of disease, all lymph nodes returned to normal size, spleen and/or liver if enlarged prior to therapy became normal or no longer palpable; or >=50% decrease in the SPD of up to 6 index lesions, no increase in size of other nodes, liver or spleen), without PD of non-index lesions (ie, without: new nonnodal lesion, new nodal lesion >=15 mm in GTD, unequivocal progression of existing non index lesions, bone marrow that was negative and is now positive, new circulating lymphoma cells in blood cell count and/or pleural fluid, new circulating blasts in the blood cell count), and without any new lesions.
|
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
|
Progression-Free Survival in Portion B
Tidsramme: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Progression-free survival in Portion B was defined as the time from Cycle 1 Day 1 to the date of the first documentation of objective PD (per Cheson 2007) or death due to any cause, whichever occurred first.
Objective PD per Cheson 2007 was defined as: PD of index lesions (>=50% increase in SPD of previously involved sites from nadir), or PD of non-index lesions (new nonnodal lesion, new nodal lesion >=15 mm in GTD, unequivocal progression of existing non index lesions, bone marrow that was negative and is now positive, new circulating lymphoma cells in blood cell count and/or pleural fluid, new circulating blasts in the blood cell count), or appearance of new lesions.
|
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
|
Overall Survival in Portion B
Tidsramme: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Overall survival was defined as the time from Cycle 1 Day 1 to the date of death due to any cause.
|
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Andre resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Biomarkers Linked With Immunomodulation and Cytokine Release
Tidsramme: Days 1, 14, 29 and 57
|
This was an exploratory endpoint and no data were collected.
|
Days 1, 14, 29 and 57
|
|
Exploratory Pharmacodynamic Biomarkers
Tidsramme: Days 1 and 21
|
This was an exploratory endpoint and no data were collected.
|
Days 1 and 21
|
|
Patient-Reported Outcomes of PF-05082566 and Rituximab When Given in Combination in Follicular Lymphoma Participants
Tidsramme: Up to 2 years
|
This was an exploratory endpoint and was not evaluated.
Patient-reported outcome questionnaires were not completed as a result of administrative processing error.
|
Up to 2 years
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Generelle publikasjoner
- Gopal AK, Levy R, Houot R, Patel SP, Popplewell L, Jacobson C, Mu XJ, Deng S, Ching KA, Chen Y, Davis CB, Huang B, Fly KD, Thall A, Woolfson A, Bartlett NL. First-in-Human Study of Utomilumab, a 4-1BB/CD137 Agonist, in Combination with Rituximab in Patients with Follicular and Other CD20+ Non-Hodgkin Lymphomas. Clin Cancer Res. 2020 Jun 1;26(11):2524-2534. doi: 10.1158/1078-0432.CCR-19-2973. Epub 2020 Mar 6.
- Segal NH, He AR, Doi T, Levy R, Bhatia S, Pishvaian MJ, Cesari R, Chen Y, Davis CB, Huang B, Thall AD, Gopal AK. Phase I Study of Single-Agent Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Patients with Advanced Cancer. Clin Cancer Res. 2018 Apr 15;24(8):1816-1823. doi: 10.1158/1078-0432.CCR-17-1922. Epub 2018 Mar 16.
Hjelpsomme linker
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Faktiske)
21. juni 2011
Primær fullføring (Faktiske)
20. februar 2019
Studiet fullført (Faktiske)
20. februar 2019
Datoer for studieregistrering
Først innsendt
28. februar 2011
Først innsendt som oppfylte QC-kriteriene
28. februar 2011
Først lagt ut (Anslag)
2. mars 2011
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
17. mars 2020
Siste oppdatering sendt inn som oppfylte QC-kriteriene
4. mars 2020
Sist bekreftet
1. mars 2020
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- Sykdommer i luftveiene
- Sykdommer i immunsystemet
- Neoplasmer etter histologisk type
- Neoplasmer
- Lymfoproliferative lidelser
- Lymfesykdommer
- Immunproliferative lidelser
- Lungesykdommer
- Urologiske neoplasmer
- Urogenitale neoplasmer
- Neoplasmer etter nettsted
- Nyresykdommer
- Urologiske sykdommer
- Adenokarsinom
- Neoplasmer, kjertel og epitel
- Neoplasmer i luftveiene
- Thoracale neoplasmer
- Karsinom, bronkogent
- Bronkiale neoplasmer
- Neoplasmer i hode og nakke
- Nevroektodermale svulster
- Neoplasmer, kjønnsceller og embryonale
- Neoplasmer, nervevev
- Nyre-neoplasmer
- Lungeneoplasmer
- Nevroendokrine svulster
- Nevi og melanomer
- Neoplasmer, plateepitelceller
- Lymfom, B-celle
- Lymfom
- Lymfom, follikulær
- Lymfom, stor B-celle, diffus
- Karsinom, nyrecelle
- Karsinom, ikke-småcellet lunge
- Karsinom
- Lymfom, Non-Hodgkin
- Melanom
- Karsinom, plateepitel
- Plateepitelkarsinom i hode og nakke
- Fysiologiske effekter av legemidler
- Antirevmatiske midler
- Antineoplastiske midler
- Immunologiske faktorer
- Antineoplastiske midler, immunologiske
- Rituximab
- Antistoffer, monoklonale
- Immunoglobulin G
Andre studie-ID-numre
- B1641001
- 2011-002799-17 (EudraCT-nummer)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
NEI
IPD-planbeskrivelse
Pfizer will provide access to individual de-identified participant data and related study documents (e.g.
protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions.
Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .