Description:
To assess the safety and tolerability at increasing dose levels of PF-06647020 in patients
with advanced solid tumors in order to determine the maximum tolerated dose and select the
recommended Phase 2 dose.
Title
- Brief Title: A Study Of PF-06647020 For Adult Patients With Advanced Solid Tumors
- Official Title: A FIRST-IN-HUMAN PHASE 1, DOSE ESCALATION, SAFETY AND PHARMACOKINETIC STUDY OF PF-06647020 IN ADULT PATIENTS WITH ADVANCED SOLID TUMORS
Clinical Trial IDs
- ORG STUDY ID:
B7661001
- SECONDARY ID:
2014-003296-36
- NCT ID:
NCT02222922
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| PF-06647020 Q3W | | PF-06647020 Q3W |
| fluconazole | | Drug-drug interaction (DDI) |
| PF-06647020 Q2W | | PF-06647020 Q2W |
| PF-06647020 combined with Avelumab | | PF-06647020 combined with Avelumab |
Purpose
To assess the safety and tolerability at increasing dose levels of PF-06647020 in patients
with advanced solid tumors in order to determine the maximum tolerated dose and select the
recommended Phase 2 dose.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| PF-06647020 Q3W | Experimental | Investigational drug infused over 60 minutes once every 21 days. | |
| Drug-drug interaction (DDI) | Experimental | PF-06647020 combined with fluconazole | |
| PF-06647020 Q2W | Experimental | Investigational drug infused over 60 minutes once every 14 days (28 day cycle) | |
| PF-06647020 combined with Avelumab | Experimental | PF-06647020 combined with Avelumab administered by infusion | - PF-06647020 combined with Avelumab
|
Eligibility Criteria
Q2W Inclusion Criteria:
- Diagnosis of platinum resistant or refractory OVCA having received 2 or fewer prior
lines, or recurrent advanced NSCLC having received 3 or fewer prior lines
- Performance Status of 0, 1, or 2
- Adequate bone marrow, kidney, and liver function
Q2W Exclusion Criteria:
- OVCA pts excluded with any of the following: non-epithelial, including malignant mixed
mullerian tumors, unresolved bowel obstruction
- Brain metastases requiring steroids
- Major surgery, radiation therapy, or systemic anti-cancer therapy within 4 weeks of
study treatment start
- Active and clinically significant bacterial, fungal, or viral infection
Q3W Inclusion Criteria:
- Diagnosis of solid tumor that is advanced/metastatic and resistant to standard therapy
or for whom no standard therapy is available
- Performance Status of 0 or 1
- Adequate bone marrow, kidney, and liver function
- Part 2 includes ovarian cancer, target expressing triple negative breast cancer and
non small cell lung cancer patients
Q3W Exclusion Criteria:
- OVCA pts excluded with any of the following: non-epithelial, including malignant mixed
mullerian tumors, prior radiotherapy to pelvis/abdomen, pts with CA-125 only disease,
unresolved bowel obstruction
- Brain metastases requiring steroids
- Major surgery, radiation therapy, or systemic anti-cancer therapy within 4 weeks of
study treatment start
- Active and clinically significant bacterial, fungal, or viral infection
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Number of Participants With Dose Limiting Toxicities (DLTs) - Q3W Regimen |
| Time Frame: | First Cycle, Day 1 up to Day 21 |
| Safety Issue: | |
| Description: | A DLT was any of the following adverse events(AEs) in the first cycle of treatment (within 21 days of first dose or until participant received second infusion if there were treatment delays). (1)Hematologic: including Grade 4 neutropenia lasting >7 days; Febrile neutropenia; Grade >=3 neutropenic infection; Grade 4 anemia; Grade >=3 thrombocytopenia with clinically significant bleeding. (2) Hepatic, including Grade >=3 serum bilirubin, hepatic transaminase or alkaline phosphatase; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >=3.0 x upper limit of normal (ULN) concurrent with elevation in bilirubin >=2.0 x ULN; (3) Grade >=3 non-hematologic, non-hepatic major organ toxicities; delayed by >2 weeks in receiving the next scheduled cycle due to persisting toxicities attributable to PF-06647020. A participant was on study for at least 21 days to be evaluable for DLT observation, and could be replaced if they terminated study participation earlier than 21 days. |
Secondary Outcome Measures
| Measure: | Area Under the Concentration-Time Profile From Time 0 to Time Tau (AUCtau) for PF-06647020 - Q3W Regimen |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle). |
| Safety Issue: | |
| Description: | Tau refers to the dosing interval and it equals to 504 hours for the Q3W dosing. AUCtau is the area under the concentration-time profile from time 0 to time tau. AUCtau for PF-06647020 was determined using linear/log trapezoidal method. |
| Measure: | Maximum Observed Serum Concentration (Cmax) for PF-06647020 -Q3W Regimen |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle). |
| Safety Issue: | |
| Description: | Cmax is maximum observed serum concentration. Cmax for PF-06647020 was observed directly from data. |
| Measure: | Clearance (CL) for PF-06647020 - Q3W Regimen |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle). |
| Safety Issue: | |
| Description: | Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance for PF-06647020 was calculated as dose/AUCinf for single dose and dose/AUCtau for multiple dose, where AUCinf was the area under the serum concentration-time profile from time 0 extrapolated to infinite time and AUCtau was the area under the concentration-time profile from time 0 to time tau (tau equals to 504 hours for the Q3W dosing). |
| Measure: | Volume of Distribution at Steady State (Vss) for PF-06647020 - Q3W Regimen |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle). |
| Safety Issue: | |
| Description: | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state. |
| Measure: | Terminal Half-Life (t1/2) for PF-06647020 - Q3W Regimen |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle). |
| Safety Issue: | |
| Description: | Terminal half-life (t1/2) is the time measured for the plasma concentration of drug to decrease by one half. |
| Measure: | Observed Accumulation Ratio (Rac) for PF-06647020 - Q3W Regimen |
| Time Frame: | pre-dose, 1, 4 hours post-dose on Day 1 of Cycle 1 and Day 1 of Cycle 4 (21 days cycle). |
| Safety Issue: | |
| Description: | Rac is defined as observed accumulation ratio based on dose normalized AUCtau (AUCtau[dn]), where AUCtau is the area under the concentration-time profile from time 0 to time tau (tau equals to 504 hours for the Q3W dosing). Rac=Cycle 4 Day 1 AUCtau(dn) (multiple dose) /Cycle 1 Day 1 AUCtau(dn) (single Dose). |
| Measure: | Time for Cmax (Tmax) for PF-06647020 - Q3W Regimen |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle). |
| Safety Issue: | |
| Description: | Tmax is the time for Cmax. Tmax for PF-06647020 was observed directly from data as time of first occurrence. |
| Measure: | Area Under the Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for PF-06647020 - Q3W Regimen |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle). |
| Safety Issue: | |
| Description: | AUClast is the area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration. AUClast for PF-06647020 was determined using linear/log trapezoidal method. |
| Measure: | Area Under the Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-06647020 - Q3W Regimen |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle). |
| Safety Issue: | |
| Description: | AUCinf is the area under the serum concentration-time profile from time 0 extrapolated to infinite time. AUCinf for PF-06647020 was calculated as AUClast + (Clast*/kel), where AUClast was the area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast* was the predicted serum concentration at the last quantifiable time point estimated from the log-linear regression analysis. kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. |
| Measure: | AUCtau for PF-06380101 - Q3W Regimen |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle). |
| Safety Issue: | |
| Description: | Tau refers to the dosing interval and it equals to 504 hours for the Q3W dosing. AUCtau is the area under the concentration-time profile from time 0 to time tau. AUCtau for PF-06380101 was determined using linear/log trapezoidal method. |
| Measure: | Cmax for PF-06380101 - Q3W Regimen |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle). |
| Safety Issue: | |
| Description: | Cmax is maximum observed serum concentration. Cmax for PF-06380101 was observed directly from data. |
| Measure: | t1/2 for PF-06380101 - Q3W Regimen |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle). |
| Safety Issue: | |
| Description: | Terminal half-life (t1/2) is the time measured for the plasma concentration of drug to decrease by one half. |
| Measure: | Rac for PF-06380101 - Q3W Regimen |
| Time Frame: | pre-dose, 1, 4 hours post-dose on Day 1 of Cycle 1 and Day 1 of Cycle 4 (21 days cycle). |
| Safety Issue: | |
| Description: | Rac is defined as observed accumulation ratio based on dose normalized AUCtau (AUCtau[dn]), where AUCtau is the area under the concentration-time profile from time 0 to time tau (tau equals to 504 hours for the Q3W dosing). Rac=Cycle 4 Day 1 AUCtau(dn) (multiple dose) /Cycle 1 Day 1 AUCtau(dn) (single Dose). |
| Measure: | Tmax for PF-06380101 - Q3W Regimen |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle). |
| Safety Issue: | |
| Description: | Tmax is the time for Cmax. Tmax for PF-06380101 was observed directly from data as time of first occurrence. |
| Measure: | AUClast for PF-06380101 - Q3W Regimen |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle). |
| Safety Issue: | |
| Description: | AUClast is the area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration. AUClast for PF-06380101 was determined using linear/log trapezoidal method. |
| Measure: | AUCinf for PF-06380101 - Q3W Regimen |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle). |
| Safety Issue: | |
| Description: | AUCinf is the area under the serum concentration-time profile from time 0 extrapolated to infinite time. AUCinf for PF-06380101 was calculated as AUClast + (Clast*/kel), where AUClast was the area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast* was the predicted serum concentration at the last quantifiable time point estimated from the log-linear regression analysis. kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. |
| Measure: | AUCtau for hu6M024 mAb - Q3W Regimen |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle). |
| Safety Issue: | |
| Description: | Tau refers to the dosing interval and it equals to 504 hours for the Q3W dosing. AUCtau is the area under the concentration-time profile from time 0 to time tau. AUCtau for hu6M024 mAb was determined using linear/log trapezoidal method. |
| Measure: | Cmax for hu6M024 mAb - Q3W Regimen |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle). |
| Safety Issue: | |
| Description: | Cmax is maximum observed serum concentration. Cmax for hu6M024 mAb was observed directly from data. |
| Measure: | t1/2 for hu6M024 mAb - Q3W Regimen |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle). |
| Safety Issue: | |
| Description: | Terminal half-life (t1/2) is the time measured for the plasma concentration of drug to decrease by one half. |
| Measure: | Rac for hu6M024 mAb - Q3W Regimen |
| Time Frame: | pre-dose, 1, 4 hours post-dose on Day 1 of Cycle 1 and Day 1 of Cycle 4 (21 days cycle). |
| Safety Issue: | |
| Description: | Rac is defined as observed accumulation ratio based on dose normalized AUCtau (AUCtau[dn]), where AUCtau is the area under the concentration-time profile from time 0 to time tau (tau equals to 504 hours for the Q3W dosing). Rac=Cycle 4 Day 1 AUCtau(dn) (multiple dose) /Cycle 1 Day 1 AUCtau(dn) (single Dose). |
| Measure: | Tmax for hu6M024 mAb - Q3W Regimen |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle). |
| Safety Issue: | |
| Description: | Tmax is the time for Cmax. Tmax for hu6M024 mAb was observed directly from data as time of first occurrence. |
| Measure: | AUClast for hu6M024 mAb - Q3W Regimen |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle). |
| Safety Issue: | |
| Description: | AUClast is the area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration. AUClast for hu6M024 mAb was determined using linear/log trapezoidal method. |
| Measure: | AUCinf for hu6M024 mAb - Q3W Regimen |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle). |
| Safety Issue: | |
| Description: | AUCinf is the area under the serum concentration-time profile from time 0 extrapolated to infinite time. AUCinf for hu6M024 mAb was calculated as AUClast + (Clast*/kel), where AUClast was the area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast* was the predicted serum concentration at the last quantifiable time point estimated from the log-linear regression analysis. kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. |
| Measure: | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) of PF-06647020 - Q3W Regimen |
| Time Frame: | Prior to the start of treatment on Day 1 of Cycle 1 up to end of treatment (approximately 31 months). |
| Safety Issue: | |
| Description: | To evaluate the immunogenicity as measured by presence of ADA and NAb in participants treated with PF-06647020. |
| Measure: | Percentage of Participants With Objective Response - Q3W Regimen |
| Time Frame: | Baseline, every 6 weeks from the start of treatment until disease progression, death or withdrawal from treatment (approximately 32 months). |
| Safety Issue: | |
| Description: | Percentage of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. |
| Measure: | Duration of Response - Q3W Regimen |
| Time Frame: | Baseline, every 6 weeks from the start of treatment until disease progression, death or withdrawal from treatment (approximately 32 months). |
| Safety Issue: | |
| Description: | Duration of response (DoR) was the time from first documentation of PR or CR to date of first documentation of progressive disease (PD) or death due to any cause. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions. |
| Measure: | Disease Control Rate - Q3W Regimen |
| Time Frame: | Baseline, every 6 weeks from the start of treatment until disease progression, death or withdrawal from treatment (approximately 32 months). |
| Safety Issue: | |
| Description: | The disease control rate (DCR) was defined as the percentage of participants with a confirmed CR, PR, non-CR/non-PD or stable disease (SD) according to the appropriate analysis set. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. |
| Measure: | Time to Progression - Q3W Regimen |
| Time Frame: | Baseline, every 6 weeks from the start of treatment until disease progression, death or withdrawal from treatment (approximately 32 months). |
| Safety Issue: | |
| Description: | Time to progression (TTP) was the time from start date to the date of the first documentation of PD. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions. |
| Measure: | Progression Free Survival - Q3W Regimen |
| Time Frame: | Baseline, every 6 weeks from the start of treatment until disease progression, death or withdrawal from treatment (approximately 32 months). |
| Safety Issue: | |
| Description: | Progression free survival (PFS) was the time from randomization date to date of first documentation of PD or death due to any cause. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions. |
| Measure: | Dose Normalized AUCinf [AUCinf(dn)] for PF-06647020 [DDI Sub-Study] |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 2 (21 days cycle). |
| Safety Issue: | |
| Description: | AUCinf is the area under the serum concentration-time profile from time 0 extrapolated to infinite time. AUCinf(dn) was defined as dose normalized AUCinf and calculated as AUCinf/dose. |
| Measure: | Dose Normalized AUClast [AUClast(dn)] for PF-06647020 [DDI Sub-Study] |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 2 (21 days cycle). |
| Safety Issue: | |
| Description: | AUClast is the area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration. AUClast(dn) was defined as dose normalized AUClast and calculated as AUClast/dose. |
| Measure: | Dose Normalized AUCtau [AUCtau(dn)] for PF-06647020 [DDI Sub-Study] |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 2 (21 days cycle). |
| Safety Issue: | |
| Description: | AUCtau is the area under the concentration-time profile from time 0 to time tau. AUCtau(dn) was defined as dose normalized AUCtau and calculated as AUCtau/dose. |
| Measure: | Dose Normalized Cmax [Cmax(dn)] for PF-06647020 [DDI Sub-Study] |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 2 (21 days cycle). |
| Safety Issue: | |
| Description: | Cmax is maximum observed serum concentration. Cmax(dn) was defined as dose normalized Cmax and calculated as Cmax/dose. |
| Measure: | AUCinf(dn) for PF-06380101 [DDI Sub-Study] |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 2 (21 days cycle). |
| Safety Issue: | |
| Description: | AUCinf is the area under the serum concentration-time profile from time 0 extrapolated to infinite time. AUCinf(dn) was defined as dose normalized AUCinf and calculated as AUCinf/dose. |
| Measure: | AUClast(dn) for PF-06380101 [DDI Sub-Study] |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 2 (21 days cycle). |
| Safety Issue: | |
| Description: | AUClast is the area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration. AUClast(dn) was defined as dose normalized AUClast and calculated as AUClast/dose. |
| Measure: | AUCtau(dn) for PF-06380101 [DDI Sub-Study] |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 2 (21 days cycle). |
| Safety Issue: | |
| Description: | AUCtau is the area under the concentration-time profile from time 0 to time tau. AUCtau(dn) was defined as dose normalized AUCtau and calculated as AUCtau/dose. |
| Measure: | Cmax(dn) for PF-06380101 [DDI Sub-Study] |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 2 (21 days cycle). |
| Safety Issue: | |
| Description: | Cmax is maximum observed serum concentration. Cmax(dn) was defined as dose normalized Cmax and calculated as Cmax/dose. |
| Measure: | AUCinf(dn) for hu6M024 mAb [DDI Sub-Study] |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 2 (21 days cycle). |
| Safety Issue: | |
| Description: | AUCinf is the area under the serum concentration-time profile from time 0 extrapolated to infinite time. AUCinf(dn) was defined as dose normalized AUCinf and calculated as AUCinf/dose. |
| Measure: | AUClast(dn) for hu6M024 mAb [DDI Sub-Study] |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 2 (21 days cycle). |
| Safety Issue: | |
| Description: | AUClast is the area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration. AUClast(dn) was defined as dose normalized AUClast and calculated as AUClast/dose. |
| Measure: | AUCtau(dn) for hu6M024 mAb [DDI Sub-Study] |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 2 (21 days cycle). |
| Safety Issue: | |
| Description: | AUCtau is the area under the concentration-time profile from time 0 to time tau. AUCtau(dn) was defined as dose normalized AUCtau and calculated as AUCtau/dose. |
| Measure: | Cmax(dn) for hu6M024 mAb [DDI Sub-Study] |
| Time Frame: | pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 2 (21 days cycle). |
| Safety Issue: | |
| Description: | Cmax is maximum observed serum concentration. Cmax(dn) was defined as dose normalized Cmax and calculated as Cmax/dose. |
| Measure: | AUCtau for PF-06647020 - Q2W Regimen |
| Time Frame: | pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle). |
| Safety Issue: | |
| Description: | Tau refers to the dosing interval and it equals to 336 hours for the Q2W dosing. AUCtau is the area under the concentration-time profile from time 0 to time tau. AUCtau for PF-06647020 was determined using linear/log trapezoidal method. |
| Measure: | Cmax for PF-06647020 -Q2W Regimen |
| Time Frame: | pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle). |
| Safety Issue: | |
| Description: | Cmax is maximum observed serum concentration. Cmax for PF-06647020 was observed directly from data. |
| Measure: | Vss for PF-06647020 - Q2W Regimen |
| Time Frame: | pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle). |
| Safety Issue: | |
| Description: | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state. |
| Measure: | CL for PF-06647020 - Q2W Regimen |
| Time Frame: | pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle). |
| Safety Issue: | |
| Description: | Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance for PF-06647020 was calculated as dose/AUCinf for single dose and dose/AUCtau for multiple dose, where AUCinf was the area under the serum concentration-time profile from time 0 extrapolated to infinite time and AUCtau was the area under the concentration-time profile from time 0 to time tau (tau equals to 336 hours for the Q2W dosing). |
| Measure: | t1/2 for PF-06647020 - Q2W Regimen |
| Time Frame: | pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle). |
| Safety Issue: | |
| Description: | Terminal half-life (t1/2) is the time measured for the plasma concentration of drug to decrease by one half. |
| Measure: | Rac for PF-06647020 - Q2W Regimen |
| Time Frame: | pre-dose, end of infusion, 4 hours post-dose on Day 1 of Cycle 1 and Day 1 of Cycle 3 (28 days cycle). |
| Safety Issue: | |
| Description: | Rac is defined as observed accumulation ratio based on dose normalized AUCtau (AUCtau[dn]), where AUCtau is the area under the concentration-time profile from time 0 to time tau (tau equals to 336 hours for the Q2W dosing). Rac= Cycle 3 Day 1 AUCtau(dn) (multiple dose) /Cycle 1 Day 1 AUCtau(dn) (single Dose). |
| Measure: | Tmax for PF-06647020 - Q2W Regimen |
| Time Frame: | pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle). |
| Safety Issue: | |
| Description: | Tmax is the time for Cmax. Tmax for PF-06647020 was observed directly from data as time of first occurrence. |
| Measure: | AUClast for PF-06647020 - Q2W Regimen |
| Time Frame: | pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle). |
| Safety Issue: | |
| Description: | AUClast is the area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration. AUClast for PF-06647020 was determined using linear/log trapezoidal method. |
| Measure: | AUCinf for PF-06647020 - Q2W Regimen |
| Time Frame: | pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle). |
| Safety Issue: | |
| Description: | AUCinf is the area under the serum concentration-time profile from time 0 extrapolated to infinite time. AUCinf was calculated as AUClast + (Clast*/kel), where AUClast was the area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast* was the predicted serum concentration at the last quantifiable time point estimated from the log-linear regression analysis. kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. |
| Measure: | AUCtau for PF-06380101 - Q2W Regimen |
| Time Frame: | pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle). |
| Safety Issue: | |
| Description: | Tau refers to the dosing interval and it equals to 336 hours for the Q2W dosing. AUCtau is the area under the concentration-time profile from time 0 to time tau. AUCtau for PF-06380101 was determined using linear/log trapezoidal method. |
| Measure: | Cmax for PF-06380101 - Q2W Regimen |
| Time Frame: | pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle). |
| Safety Issue: | |
| Description: | Cmax is maximum observed serum concentration. Cmax for PF-06380101 was observed directly from data. |
| Measure: | t1/2 for PF-06380101 - Q2W Regimen |
| Time Frame: | pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle). |
| Safety Issue: | |
| Description: | Terminal half-life (t1/2) is the time measured for the plasma concentration of drug to decrease by one half. |
| Measure: | Rac for PF-06380101 - Q2W Regimen |
| Time Frame: | pre-dose, end of infusion, 4 hours post-dose on Day 1 of Cycle 1 and Day 1 of Cycle 3 (28 days cycle). |
| Safety Issue: | |
| Description: | Rac is defined as observed accumulation ratio based on dose normalized AUCtau (AUCtau[dn]), where AUCtau is the area under the concentration-time profile from time 0 to time tau (tau equals to 336 hours for the Q2W dosing). Rac= Cycle 3 Day 1 AUCtau(dn) (multiple dose) /Cycle 1 Day 1 AUCtau(dn) (single Dose). |
| Measure: | Tmax for PF-06380101 - Q2W Regimen |
| Time Frame: | pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle). |
| Safety Issue: | |
| Description: | Tmax is the time for Cmax. Tmax for PF-06380101 was observed directly from data as time of first occurrence. |
| Measure: | AUClast for PF-06380101- Q2W Regimen |
| Time Frame: | pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle). |
| Safety Issue: | |
| Description: | AUClast is the area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration. AUClast for PF-06380101 was determined using linear/log trapezoidal method. |
| Measure: | AUCinf for PF-06380101- Q2W Regimen |
| Time Frame: | pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle). |
| Safety Issue: | |
| Description: | AUCinf is the area under the serum concentration-time profile from time 0 extrapolated to infinite time. AUCinf was calculated as AUClast + (Clast*/kel), where AUClast was the area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast* was the predicted serum concentration at the last quantifiable time point estimated from the log-linear regression analysis. kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. |
| Measure: | AUCtau for hu6M024 mAb- Q2W Regimen |
| Time Frame: | pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle). |
| Safety Issue: | |
| Description: | Tau refers to the dosing interval and it equals to 336 hours for the Q2W dosing. AUCtau is the area under the concentration-time profile from time 0 to time tau. AUCtau for hu6M024 mA was determined using linear/log trapezoidal method. |
| Measure: | Cmax for hu6M024 mAb -Q2W Regimen |
| Time Frame: | pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle). |
| Safety Issue: | |
| Description: | Cmax is maximum observed serum concentration. Cmax for hu6M024 mAb was observed directly from data. |
| Measure: | t1/2 for hu6M024 mAb - Q2W Regimen |
| Time Frame: | pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle). |
| Safety Issue: | |
| Description: | Terminal half-life (t1/2) is the time measured for the plasma concentration of drug to decrease by one half. |
| Measure: | Rac for hu6M024 mAb - Q2W Regimen |
| Time Frame: | pre-dose, end of infusion, 4 hours post-dose on Day 1 of Cycle 1 and Day 1 of Cycle 3 (28 days cycle). |
| Safety Issue: | |
| Description: | Rac is defined as observed accumulation ratio based on dose normalized AUCtau (AUCtau[dn]), where AUCtau is the area under the concentration-time profile from time 0 to time tau (tau equals to 336 hours for the Q2W dosing). Rac= Cycle 3 Day 1 AUCtau(dn) (multiple dose) /Cycle 1 Day 1 AUCtau(dn) (single Dose). |
| Measure: | Tmax for hu6M024 mAb - Q2W Regimen |
| Time Frame: | pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle). |
| Safety Issue: | |
| Description: | Tmax is the time for Cmax. Tmax for hu6M024 mAb was observed directly from data as time of first occurrence. |
| Measure: | AUClast for hu6M024 mAb - Q2W Regimen |
| Time Frame: | pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle). |
| Safety Issue: | |
| Description: | AUClast is the area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration. AUClast for hu6M024 mAb was determined using linear/log trapezoidal method. |
| Measure: | AUCinf for hu6M024 mAb - Q2W Regimen |
| Time Frame: | pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle). |
| Safety Issue: | |
| Description: | AUCinf is the area under the serum concentration-time profile from time 0 extrapolated to infinite time. AUCinf was calculated as AUClast + (Clast*/kel), where AUClast was the area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast* was the predicted serum concentration at the last quantifiable time point estimated from the log-linear regression analysis. kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. |
| Measure: | Number of Participants With ADA and NAb of PF-06647020 - Q2W Regimen |
| Time Frame: | 2 hours before the first dose up to 30 days after the last dose (approximately 18 months). |
| Safety Issue: | |
| Description: | To evaluate the immunogenicity as measured by presence of ADA and NAb in participants treated with PF-06647020. |
| Measure: | Percentage of Participants With Objective Response - Q2W Regimen |
| Time Frame: | Baseline, every 8 weeks from the start of study treatment until disease progression, death or withdrawal from treatment (approximately 19 months). |
| Safety Issue: | |
| Description: | Percentage of participants with objective response based on assessment of CR or PR according to RECIST version 1.1. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. |
| Measure: | Duration of Response - Q2W Regimen |
| Time Frame: | Baseline, every 8 weeks from the start of study treatment until disease progression, death or withdrawal from treatment (approximately 19 months). |
| Safety Issue: | |
| Description: | For participants with an objective response, duration of response (DoR) was the time from first documentation of PR or CR to date of first documentation of PD or death due to any cause. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions. |
| Measure: | Disease Control Rate - Q2W Regimen |
| Time Frame: | Baseline, every 8 weeks from the start of study treatment until disease progression, death or withdrawal from treatment (approximately 19 months). |
| Safety Issue: | |
| Description: | The disease control rate (DCR) was defined as the percentage of participants with a confirmed CR, PR or SD according to the appropriate analysis set. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. |
| Measure: | Time to Progression - Q2W Regimen |
| Time Frame: | Baseline, every 8 weeks from the start of study treatment until disease progression, death or withdrawal from treatment (approximately 19 months). |
| Safety Issue: | |
| Description: | Time to progression (TTP) was the time from start date to the date of the first documentation of PD. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions. |
| Measure: | Progression Free Survival - Q2W Regimen |
| Time Frame: | Baseline, every 8 weeks from the start of study treatment until disease progression, death or withdrawal from treatment (approximately 19 months). |
| Safety Issue: | |
| Description: | Progression free survival (PFS) was the time from randomization date to date of first documentation of PD or death due to any cause. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions. |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Pfizer |
Trial Keywords
- ADC
- PF-06647020
- solid tumors
- tumors
- neoplasm metastasis
- TNBC
- triple negative breast cancer
- NSCLC
- non small cell lung cancer
- advanced metastatic breast cancer
- ovarian cancer
- OVCA
Last Updated
December 17, 2020
