Study Of OX40 Agonist PF-04518600 Alone And In Combination With 4-1BB Agonist PF-05082566
- Registration Number
- NCT02315066
- Lead Sponsor
- Pfizer
- Brief Summary
To assess the safety and tolerability at increasing dose levels of PF-04518600 alone or in combination wtih PF-05082566 in patients with select advanced or metastatic carcinoma in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 174
- Part A1 only: Patients with histological or cytological diagnosis of HNSCC, HCC, melanoma, or clear cell RCC who progressed on or are intolerant to standard therapy, for which no standard therapy is available or who decline standard therapy.
- Part A2 only: Patients with histological or cytological diagnosis of advanced/metastatic HCC who are treatment naïve and have declined standard of care, or have had at least 1 prior line of systemic therapy. Prior anti PD L1/PD 1 therapy is allowed.
- Part B1 only: Patients with histological or cytological diagnosis of NSCLC, HNSCC, melanoma, urothelial bladder carcinoma (including renal pelvis, ureters, urinary bladder, and urethra), gastric or squamous cell carcinoma of the uterine cervix who progressed on or are intolerant to standard therapy, for which no standard therapy is available, or who decline standard therapy.
- Part B2
Arm 1 only:
- Ocular melanoma patients with advanced/metastatic disease, or
- Cutaneous/acral melanoma patients with advanced/metastatic disease who have received checkpoint inhibitor (anti PD L1, anti PD 1, or anti CTLA4) based treatment on which disease progressed. [Note: Checkpoint inhibitor may have been part of a combination therapy, as long as the combination did not contain OX40 or 4 1BB agonist.] Any questions on prior treatment may be discussed with the Sponsor.
Arm 2 only:
- Histological or cytological diagnosis of NSCLC with advanced/metastatic disease. Patients must have previously received prior anti PD L1 or anti PD 1 mAb on which disease progressed. [Note: Previous anti PD L1 or anti PD 1 mAb may have been part of a combination therapy, eg, in combination with chemotherapy, as long as the combination did not contain OX40 or 4 1BB agonist.]
- Performance Status of 0 or 1 - Adequate bone marrow, kidney and liver function
- Brain metastases requiring steroids
- Major surgery, Radiation therapy within 4 weeks of starting study treatment (except: palliative radiotherapy to a limited field is allowed after consultation with sponsor's medical monitor at any time during study participation, including during screening), or systemic anti-cancer therapy within 4 weeks of study treatment start (6 weeks for mitomycin C or nitrosoureas)
- Active and clinically significant bacterial, fungal, or viral infection
- History of active autoimmune disorders
- History of immune-mediated adverse events requiring immunosuppressive therapy or were grade 3 or higher related to prior immune-modulatory therapy
- Prior treatment with an OX40 agonist and 4-1BB agonist (for Part B1/B2)
- Prior anthracycline treatment and at risk of cardiac failure (New York Heart Association Class 2)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description PF-04518600 plus PF-05082566 PF-04518600 plus PF-05082566 OX40 (CD134) agonist plus 4-1BB (CD137) agonist PF-04518600 PF-04518600 OX40 agonist
- Primary Outcome Measures
Name Time Method Number of Participants With Laboratory Test Abnormalities in Part B The first dosing date to the earlier date between the last dosing date + 35 days and the first new anti-cancer therapy date (if applicable) Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, partial thromboplastin time (PTT), Prothrombin (PT), PT international ratio); liver function (aspartate aminotransferase(AST), alanine aminotransferase(ALT), total bilirubin, gamma-glutamyl transpeptidase(GT), alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium , phosphate, magnesium); clinical chemistry (glucose, creatine kinase, thyroxine (T4), thyroid stimulating hormone(TSH)), Amylase, Lipase), urinalysis (dipstick \[protein, blood\], microscopy \[urine red blood cell (RBC), white blood cell (WBC), Epithelial Cells\], miscellaneous \[urine casts and bacteria\]).
Number of Participants With All-Causality Treatment Emergent Adverse Events(TEAEs) and Serious Adverse Event(SAEs), Treatment-Related TEAEs and SAEs in Part A AEs: The informed consent date up to the last dosing date + 28 days or all drug-related toxicities resolved date. SAEs: The informed consent date through first dosing date + 98 days or up to the last dosing date + 60 days, and any post-reporting period. Adverse event (AE) was graded by the investigator according to CTCAE version 4.03 and coded using the Medical Dictionary for Regulatory Activities (MedDRA): Grade 3 (Severe) events=unacceptable or intolerable events. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 (Death) events=death related to an AE. Treatment-emergent events=between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state. TEAEs were defined as those with initial onset or increasing in severity after the first dose of study medication. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Number of Participants With Laboratory Test Abnormalities in Part A The first dosing date to the earlier date between the last dosing date + 35 days and the first new anti-cancer therapy date (if applicable) Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, partial thromboplastin time (PTT), Prothrombin (PT), PT international ratio); liver function (aspartate aminotransferase(AST), alanine aminotransferase(ALT), total bilirubin, gamma-glutamyl transpeptidase(GT), alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium , phosphate, magnesium); clinical chemistry (glucose, creatine kinase, thyroxine (T4), thyroid stimulating hormone(TSH)), Amylase, Lipase), urinalysis (dipstick \[protein, blood\], microscopy \[urine red blood cell (RBC), white blood cell (WBC), Epithelial Cells\], miscellaneous \[urine casts and bacteria\]).
Number of Participants With All-causality TEAEs and SAEs, and Treatment-Related TEAEs and SAEs in Part B AEs: The informed consent date up to the last dosing date + 60 days or all drug-related toxicities resolved date. SAEs: The informed consent date through first dosing date + 98 days or up to the last dosing date + 60 days, and any post-reporting period. Adverse event (AE) was graded by the investigator according to CTCAE version 4.03 and coded using the Medical Dictionary for Regulatory Activities (MedDRA): Grade 3 (Severe) events=unacceptable or intolerable events. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 (Death) events=death related to an AE. Treatment-emergent events=between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state. TEAEs were defined as those with initial onset or increasing in severity after the first dose of study medication. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Number of Participants With Dose Limiting Toxicities (DLTs) in Part A1 The first 2 cycles of treatment (Day 1 up to Day 28) DLT was defined as any of the following adverse events occurring in the first two cycle of treatment (28 days), unless there was a clear alternative explanation: hematologic: grade 4 neutropenia lasting \>7 days, febrile neutropenia; grade ≥3 neutropenic infection; grade ≥3 thrombocytopenia with clinically significant bleeding or requiring medical intervention; grade 4 thrombocytopenia; grade 4 anemia; grade ≥3 anemia related to hemolysis or autoimmune disease. non hematologic: grade ≥3 toxicities that were considered clinically significant, including cytokine release syndrome, infusion reactions and allergic reactions, except those that had not been maximally treated or could be easily treated. The severity of adverse events was graded as per common terminology criteria for adverse events(CTCAE) version 4.03, and there were no DLTs reported.
Number of Participants With DLTs in Part B1 The First 2 Cycles of Treatment (Day 1 up to Day 28) DLT was defined as any of the following adverse events occurring in the first two cycle of treatment (28 days), unless there was a clear alternative explanation: hematologic: grade 4 neutropenia lasting \>7 days, febrile neutropenia; grade ≥3 neutropenic infection; grade ≥3 thrombocytopenia with clinically significant bleeding or requiring medical intervention; grade 4 thrombocytopenia; grade 4 anemia; grade ≥3 anemia related to hemolysis or autoimmune disease. non hematologic: grade ≥3 toxicities that were considered clinically significant, including cytokine release syndrome, infusion reactions and allergic reactions, except those that had not been maximally treated or could be easily treated. The severity of adverse events was graded as per common terminology criteria for adverse events(CTCAE) version 4.03, and there were no DLTs reported.
- Secondary Outcome Measures
Name Time Method Kaplan-Meier Estimate of Median Progression-Free Survival (PFS) in Part A Baseline up to 24 months post first dose PFS was defined as the time from randomization date to date of first documentation of progressive disease(PD) based on RECIST, irRECIST or death due to any cause.
PD was progression documented after start date and not qualifying as CR, PR or SD per RECIST.Kaplan-Meier Estimate of Median Time to Progression (TTP) in Part A Baseline up to 24 months post first dose TTP was defined as the time from start date to the date of the first documentation of PD. PD was documented after start date and not qualifying as CR, PR or SD per RECIST.
Maximum Serum Concentration (Cmax) of PF-04518600 Following Single Dose on Cycle 1 Day 1 (C1D1) and Steady-State Maximum Serum Concentration(Css,Max) Following Multiple Doses on Cycle 3 Day 1 (C3D1) in Part A For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. Cmax was defined as maximum observed serum concentration and can be observed directly from data.
Css,max was the Cmax on C3D1.Clearance (CL) of PF-04518600 Following Multiple Doses on C3D1 in Part A For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. Drug clearance was a quantitative measure of the rate at which a drug substance is removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes). CL=Dose/AUCss,tau
Lowest Serum Concentration Observed During the Dosing Interval (Cmin) of PF-04518600 Following Multiple Doses on C3D1 in Part A. For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. Cmin was defined as Lowest concentration observed during the dosing interval and can be observed directly from data.
ORR Assessed by RECIST Version 1.1 and irRECIST in Part B Baseline up to 24 months post first dose. ORR was defined as the percentage of patients with best overall response (BOR) of CR or PR relative to the appropriate analysis set.
CR: Complete response is defined (per RECIST 1.1) as disappearance of all target and non target lesions. Any pathological lymph nodes (whether target or non target) must have reduction in short axis to \<10 mm.
PR: Partial response is difined (per RECIST 1.1) as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Overall immune related complete response (irCR): Complete disappearance of all lesions (whether measurable or not) and no new lesions. All measurable lymph nodes also must have a reduction in short axis to \<10 mm.
Overall immune related partial response (irPR): Sum of the diameters (longest for non nodal lesions, shortest for nodal lesions) of target and new measurable lesions decreases ≥30%.Objective Response Rate (ORR) Assessed by Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 and Immune Related Response Evaluation Criteria in Solid Tumors (irRECIST) in Part A Baseline up to 24 months post first dose. ORR was defined as the percentage of patients with best overall response (BOR) of CR or PR relative to the appropriate analysis set.
CR: Complete response is defined (per RECIST 1.1) as disappearance of all target and non target lesions. Any pathological lymph nodes (whether target or non target) must have reduction in short axis to \<10 mm.
PR: Partial response is difined (per RECIST 1.1) as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Overall immune related complete response (irCR): Complete disappearance of all lesions (whether measurable or not) and no new lesions. All measurable lymph nodes also must have a reduction in short axis to \<10 mm.
Overall immune related partial response (irPR): Sum of the diameters (longest for non nodal lesions, shortest for nodal lesions) of target and new measurable lesions decreases ≥30%.Overall Survival Rates at Months 6, 12, and 24 in Part A Baseline up to 24 months post first dose. Probability of survival at 6, 12, and 24 months after the first dose of study treatment.
Terminal Half-Life (t1/2) of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part A For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. t1/2 was defined as the time measured for the serum concentration to decrease by one half of the initial concentration.
Average Serum Concentration Over the Dosing Interval (Cav) of PF-04518600 Following Multiple Doses on C3D1 in Part A For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. Cav was defined as average serum concentration over the dosing interval.
Kaplan-Meier Estimate of Median Overall Survival (OS) in Part A Baseline up to 24 months post first dose. OS was defined as time in months from the start of study treatment to date of death due to any cause. OS was calculated as the death date or last known alive date (if death date unavailable) minus the date of first dose of study medication plus 1 divided by 30.44.
Area Under the Concentration-Time Profile From Time 0 to Time Tau (AUCtau) of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part A For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. AUCtau was defined as area under the concentration curve from time 0 to end of dosing interval where dosing interval was 2 weeks.
Number of Participants With Anti Drug Antibody (ADA) and Neutralizing Antibody (NAb) Against PF-04518600 in Part A Baseline up to end of treatment (maximum of 14 weeks). ADA never-positive was defined as no positive ADA results at any time point. ADA ever-positive was defined as at least one positive ADA result at any time point. nAb never-positive was defined as no positive nAb results at any time point and nAb ever-positive was defined as at least one positive nAb result at any time point.
Number of Participants Having Stable Disease (SD) in Part A Baseline up to 24 months post first dose. SD was defined as persistence of any non target lesions and/or tumor marker level above the normal limits.
Kaplan-Meier Estimate of Median Duration of Response (DoR) in Part A Baseline up to 24 months post first dose. DoR was defined as the time from first documentation of PR or CR to date of first documentation of PD or death due to any cause for patients with an objective response.
CR was defined as complete disappearance of all target lesions with the exception of nodal disease and all target nodes must decrease to normal size (short axis \<10 mm) and all target lesions must be assessed.
PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter is used in the sum for target nodes, while the longest diameter is used in the sum for all other target lesions and all target lesions must be assessed.Area Under the Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part A For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. AUCinf was defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It was obtained from AUC (0-t) plus AUC (t-inf).
Apparent Volume of Distribution at Steady State (Vss) of PF-04518600 Following Multiple Doses on C3D1 in Part A. For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. Vss was defined as volume of distribution at steady state.
Mean Unbound Cell Surface OX40 in Part A1 Pre-dose, 4 and 24 hours post dose on Cycle 1 Day 1, and Day 8 on Cycles 1 to 3, then pre-dose on Cycles 4 and 7 and end of treatment in Part A1 Mean unbound cell surface OX40 in peripheral blood was measured to characterize the degree of target engagement (TE) by PF-04518600 at baseline and multiple doses.
AUCtau of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. AUCtau was defined as area under the concentration curve from time 0 to end of dosing interval where dosing interval was 2 weeks.
CL of Utomilumab Following Multiple Doses on C3D1 in Part B For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. Drug clearance was a quantitative measure of the rate at which a drug substance is removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes). CL=Dose/AUCss,tau
Accumulation Ratio (Rac) of PF-04518600 at C3D1 Following Multiple Doses on C3D1 in Part A For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. Accumulation ratio was calculated as, Rac obtained from Area Under the Concentration Time Curve (AUC) from Cycle 3 Day 1 divided by AUC from Cycle1 Day 1.
Kaplan-Meier Estimate of Median PFS in Part B Baseline up to 24 months post first dose. PFS was defined as the time from randomization date to date of first documentation of progressive disease(PD) based on RECIST, irRECIST or death due to any cause.
PD was progression documented after start date and not qualifying as CR, PR or SD per RECIST.Kaplan-Meier Estimate of Median OS in Part B Baseline up to 24 months post first dose. OS was defined as time in weeks or months from the start of study treatment to date of death due to any cause. OS was calculated as the death date or last known alive date (if death date unavailable) minus the date of first dose of study medication plus 1 divided by 7 or 30.44 if in months.
Cmax of PF-04518600 Following Single Dose on C1D1 and Css,Max Following Multiple Doses on C3D1 in Part B For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. Cmax was defined as maximum observed serum concentration and can be observed directly from data.
Css,max was the Cmax on C3D1.Cav of PF-04518600 Following Multiple Doses on C3D1 in Part B For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. Cav was defined as average serum concentration over the dosing interval.
Rac of Utomilumab Following Multiple Doses on C3D1 in Part B For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. Accumulation ratio was calculated as, Rac obtained from Area Under the Concentration Time Curve (AUC) from Cycle 3 Day 1 divided by AUC from Cycle1 Day 1.
Kaplan-Meier Estimate of Median TTP in Part B Baseline up to 24 months post first dose. TTP was defined as the time from start date to the date of the first documentation of PD. PD was documented after start date and not qualifying as CR, PR or SD per RECIST.
t1/2 of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. t1/2 was defined as the time measured for the serum concentration to decrease by one half of the initial concentration.
Cmax of Utomilumab Following Single Dose on C1D1 and Css,Max Following Multiple Doses on C3D1 in Part B For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. Cmax was defined as maximum observed serum concentration and can be observed directly from data.
Css,max was the Cmax on C3D1.AUCinf of Utomilumab Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. AUCinf was defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It was obtained from AUC (0-t) plus AUC (t-inf).
Number of Participants Having SD in Part B Baseline up to 24 months post first dose. SD was defined as persistence of any non target lesions and/or tumor marker level above the normal limits.
Kaplan-Meier Estimate of Median DoR in Part B Baseline up to 24 months post first dose. DoR was defined as the time from first documentation of PR or CR to date of first documentation of PD or death due to any cause for patients with an objective response.
CR was defined as complete disappearance of all target lesions with the exception of nodal disease and all target nodes must decrease to normal size (short axis \<10 mm) and all target lesions must be assessed.
PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter is used in the sum for target nodes, while the longest diameter is used in the sum for all other target lesions and all target lesions must be assessed.Overall Survival Rates at Months 6, 12, and 24 in Part B Baseline up to 24 months post first dose. Probability of survival at 6, 12, and 24 months after the first dose of study treatment.
Cmin of PF-04518600 Following Multiple Doses on C3D1 in Part B For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. Cmin was defined as Lowest concentration observed during the dosing interval and can be observed directly from data.
CL of PF-04518600 Following Multiple Doses on C3D1 in Part B For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. Drug clearance was a quantitative measure of the rate at which a drug substance is removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes). CL=Dose/AUCss,tau
Vss of Utomilumab Following Multiple Doses on C3D1 in Part B For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. Vss was defined as volume of distribution at steady state.
AUCinf of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. AUCinf was defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It was obtained from AUC (0-t) plus AUC (t-inf).
Vss of PF-04518600 Following Multiple Doses on C3D1 in Part B For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. Vss was defined as volume of distribution at steady state.
Rac of PF-04518600 Following Multiple Doses on C3D1 in Part B For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. Accumulation ratio was calculated as, Rac obtained from Area Under the Concentration Time Curve (AUC) from Cycle 3 Day 1 divided by AUC from Cycle1 Day 1.
AUCtau of Utomilumab Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. AUCtau was defined as area under the concentration curve from time 0 to end of dosing interval where dosing interval was 2 weeks.
t1/2 of Utomilumab Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. t1/2 was defined as the time measured for the serum concentration to decrease by one half of the initial concentration.
Cmin of Utomilumab Following Multiple Doses on C3D1 in Part B For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. Cmin was defined as Lowest concentration observed during the dosing interval and can be observed directly from data.
Cav of Utomilumab Following Multiple Doses on C3D1 in Part B For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. Cav was defined as average serum concentration over the dosing interval.
Number of Participants With ADA and NAb Against PF-04518600 in Part B Baseline up to end of treatment (maximum of 14 weeks). ADA never-positive was defined as no positive ADA results at any time point. ADA ever-positive was defined as at least one positive ADA result at any time point. nAb never-positive was defined as no positive nAb results at any time point and nAb ever-positive was defined as at least one positive nAb result at any time point.
Number of Participants With ADA and NAb Against Utomilumab in Part B Baseline up to end of treatment (maximum of 14 weeks). ADA never-positive was defined as no positive ADA results at any time point. ADA ever-positive was defined as at least one positive ADA result at any time point. nAb never-positive was defined as no positive nAb results at any time point and nAb ever-positive was defined as at least one positive nAb result at any time point.
Trial Locations
- Locations (30)
The Angeles Clinic And Research Institute, A Cedars-Sinai Affiliate
🇺🇸Los Angeles, California, United States
LAC+USC Medical Center
🇺🇸Los Angeles, California, United States
Beth Israel Deaconess Medical Center (BIDMC)
🇺🇸Boston, Massachusetts, United States
USC/Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
UCLA Hematology & Oncology Clinic
🇺🇸Los Angeles, California, United States
Ronald Regan Medical Center
🇺🇸Los Angeles, California, United States
Santa Monica UCLA Hematology & Oncology Clinic
🇺🇸Santa Monica, California, United States
Medical Imaging Center of Southern California, Inc.
🇺🇸Santa Monica, California, United States
UConn Health, Neag Comprehensive Cancer Center
🇺🇸Farmington, Connecticut, United States
Brigham & Women's Hospital (BWH)
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute (DFCI)
🇺🇸Boston, Massachusetts, United States
Hoag Memorial Hospital Presbyterian
🇺🇸Newport Beach, California, United States
H. Lee Moffitt Cancer Center & Research Institute
🇺🇸Tampa, Florida, United States
UConn Health, Pharmacy
🇺🇸Farmington, Connecticut, United States
Keck Hospital of USC
🇺🇸Los Angeles, California, United States
Massachusetts General Hospital (MGH)
🇺🇸Boston, Massachusetts, United States
Mass General/North Shore Center for Outpatient Care
🇺🇸Danvers, Massachusetts, United States
Massachusetts General/Chelsea HealthCare Center
🇺🇸Chelsea, Massachusetts, United States
Mass General West
🇺🇸Waltham, Massachusetts, United States
Columbia University Medical Center - Herbert Irving Pavilion
🇺🇸New York, New York, United States
Methodist Hospital-Pathology
🇺🇸Houston, Texas, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Institut Gustave Roussy
🇫🇷Villejuif, France
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
The Netherlands Cancer Institute
🇳🇱Amsterdam, Netherlands
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
Slotervaart Hospital/Antoni van Leeuwenhoek
🇳🇱Amsterdam, Netherlands
Groupe hospitalier Pitie Salpetriere
🇫🇷Paris, France
Erasmus MC
🇳🇱Rotterdam, Netherlands