Neoplasms
Conditions
Keywords
ADC, PF-06664178, solid tumors, tumors, neoplasm metastasis, NSCLC, non small cell lung cancer, OVCA, ovarian cancer, Phase 1, breast cancer
Brief summary
To assess the safety and tolerability at increasing dose levels of PF-06664178 in patients with advanced solid tumors in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.
Interventions
DRUGPF-06664178
Part 1 - PF-06664178 will be administered intravenously every 21 days in cohorts of 2 or more patients starting at a dose of 0.15 mg/kg. Increases in dose will continue until MTD is determined.
Sponsors
Pfizer
Study design
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 target expressing NSCLC, ovarian or breast cancer patients
Exclusion criteria
* Brain metastases requiring steroids * Major surgery, radiation therapy, 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| First Cycle Dose Limiting Toxicities (DLTs) In Order to Determine the Maximum Tolerated Dose(MTD) | Day 1 up to Day 21 | Number of participants that experienced dose limiting toxicities(DLTs) at given dose level. |
| Number of Patients With All-Causality Treatment-Emergent Adverse Events(TEAEs) [Part 2 & 3] | Day 1 up to Day 21 | An adverse event (AE) was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug. |
| Number of Participants With Laboratory Abnormalities [Part 2 & 3] | On Day1, Day4, Day8, Day15 of the first cycle; on Day1, Day8, Day15 of the second cycle; on Day 1 of the subsequent cycles; end of treatment visit(no longer than 1 week after the patient has been discontinued) | Number of participants with a laboratory abnormality meeting specified criteria. The laboratory test included: hematology( hemoglobin, platelets, white blood cell count, absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils, absolute basophils), chemistry (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen or urea, creatinine, uric acid, glucose, albumin, phosphorous or phosphate), coagulation (prothrombin time or International normalized ratio, partial thromboplastin time), Urinalysis (urine protein, urine blood) and pregnancy test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Incidence of Anti-PF-06664178-Antibodies[Part 1] | Day 1, 15, 21, and every 21 days thereafter up to 24 months, and end of treatment | Number of participants with the presence of anti-PF-06664178 antibodies |
| Overall Incidence of Anti-PF-06664178-Antibodies [Part 2 & 3] | Day 1, 15, 21, and every 21 days thereafter up to 24 months, and end of treatment | Number of participants with the presence of anti-PF-06664178 antibodies |
| Overall Number of Participants With Objective Tumor Response[Part 1] | Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months | Objective tumor response, was assessed using the Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 by calculating the Overall Response Rate, and Prolonged Stable Disease. The criterion is defined as: Objective Progression(PD):20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5mm; Stable (SD): All target lesions must be assessed. Stable can follow PR only in the rare case that the sum increases by less than 20% from the nadir, but enough that a previously documented 30% decrease no longer holds; symptomatic deterioration(Sym):Participants with a global deterioration of health status requiring discontinuation of treatment without objective evidence of disease progression at that time; Indeterminate (In):Progression has not been determined and one, or more non-target sites were not assessed, or assessment methods were inconsistent with those used at baseline. |
| Maximum Observed Plasma Concentration (Cmax) for PF-06664178 [Part 1 ,2 & 3] | 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment | Cmax of PF-06664178 was observed directly from data |
| Maximum Observed Plasma Concentration (Cmax) for Total Antibody (PF-06479118) [Part 1 ,2 & 3] | 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment | Cmax of total antibody PF-06479118 was observed directly from data |
| Maximum Observed Plasma Concentration (Cmax) for Unconjugated Payload (PF-06380101) [Part 1 ,2 & 3] | 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment | Cmax of unconjugated payload PF-06380101 was observed directly from data |
| Area Under the Concentration-Time Curve Over the Dosing Interval(AUCtau) of PF-06664178 [Part 1 ,2 & 3] | 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment | AUCtau refers to area under the concentration-time profile from time zero to the time tau, the dosing interval |
| Area Under the Concentration-Time Curve Over the Dosing Interval(AUCtau) of Total Antibody(PF-06479118) [Part 1 ,2 & 3] | 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment | AUCtau refers to area under the concentration-time profile from time zero to the time tau, the dosing interval. |
| Area Under the Concentration-Time Curve Over the Dosing Interval(AUCtau) of Unconjugated Payload(PF-06380101) [Part 1 ,2 & 3] | 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment | AUCtau refers to area under the concentration-time profile from time zero to the time tau, the dosing interval. |
| Systemic Clearance (CL) of PF-06664178 [Part 1 ,2 & 3] | 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment | CL is a quantitative measure of the rate at which a drug substance is removed from the body. |
| Systemic Clearance (CL) of Total Antibody (PF-06479118) [Part 1 ,2 & 3] | 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment | CL is a quantitative measure of the rate at which a drug substance is removed from the body. |
| Overall Number of Participants With Objective Tumor Response [Part 2 & 3] | Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months | Objective tumor response, as assessed using the Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 by calculating the Overall Response Rate (ORR), and Prolonged Stable Disease (SD).No Progression Free Survival (PFS) was completed. The criterion is as follow: Objective Progression(PD), Stable (SD), symptomatic deterioration(Sym), and Indeterminate (In) |
| Volume of Distribution (Vss) of PF-06664178 [Part 1 ,2 & 3] | 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment | 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. |
| Volume of Distribution (Vss) of Total Antibody (PF-06479118) [Part 1 ,2 & 3] | 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment | 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. |
| Volume of Distribution (Vss) of Unconjugated Payload (PF-06380101) [Part 1 ,2 & 3] | 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment | 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. |
| Terminal Elimination Half-Life (t1/2) of PF-06664178 [Part 1 ,2 & 3] | 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment | Terminal elimination half-life is the time measured for the plasma concentration to decrease by one half |
| Terminal Elimination Half-Life (t1/2) of Total Antibody (PF-06479118)[Part 1 ,2 & 3] | 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment | Terminal elimination half-life is the time measured for the plasma concentration to decrease by one half |
| Terminal Elimination Half-Life (t1/2) of Unconjugated Payload (PF-06380101) [Part 1 ,2 & 3] | 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment | Terminal elimination half-life is the time measured for the plasma concentration to decrease by one half |
| Trop-2 Expression Levels on Archived Tissue [Part 2 & 3] | Day 1 | Number of participents meeting the following criterion for Trop-2 expression assessment : low expression, medium expression and high expression |
| Accumulation Ratio (Rac) of PF-06664178 [Part 1 ,2 & 3] | 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment | Accumulation ratio refers to AUCtau for cycle 4/AUCtau for cycle 1, where AUCtau is defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to the time tau, the dosing interval. |
| Accumulation Ratio (Rac) of Total Antibody (PF-06479118) [Part 1 ,2 & 3] | 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment | Accumulation ratio refers to AUCtau for cycle 4/AUCtau for cycle 1, where AUCtau is defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to the time tau, the dosing interval. |
| Accumulation Ratio (Rac) of Unconjugated Payload (PF-06380101) [Part 1 ,2 & 3] | 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment | Accumulation ratio refers to AUCtau for cycle 4/AUCtau for cycle 1, where AUCtau is defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to the time tau, the dosing interval. |
| Systemic Clearance (CL) of Unconjugated Payload (PF-06380101) [Part 1 ,2 & 3] | 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment | CL is a quantitative measure of the rate at which a drug substance is removed from the body. |
| Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs ) [Part 1] | From screening up to 28 days after the last treatment administration in each cycle, and follow-up visits(At least 28 days and no more than 35 days after discontinuation of treatment) | An adverse event (AE) was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug. |
| Number of Participants With Laboratory Abnormalities[Part 1] | Screening; on Day1, Day4, Day8, Day15 of the first cycle; on Day1, Day8, Day15 of the second cycle; on Day 1 of the subsequent cycles; end of treatment visit(no longer than 1 week after the patient has been discontinued) | Number of participants with a laboratory abnormality meeting specified criteria. The laboratory test included: hematology( hemoglobin, platelets, white blood cell count, absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils, absolute basophils), chemistry (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen or urea, creatinine, uric acid, glucose, albumin, phosphorous or phosphate), coagulation (prothrombin time or International normalized ratio, partial thromboplastin time), Urinalysis (urine protein, urine blood) and pregnancy test. |
Countries
United States
Participant flow
Pre-assignment details
A total of 38 patients were screened, among which 31 were assigned to study treatment.
Participants by arm
| Arm | Count |
|---|---|
| PF-06664178 0.15 mg/kg Participants were enrolled in cohorts of 2-4 to receive PF-06664178 in an open-label, unblinded manner and treated with PF-06664178 in 7 sequential dose levels between 0.15 and 4.8 mg/kg. PF-06664178 0.15 mg/kg was administered on Day 1 of each 21-day cycle per the dose administration instructions (DAI) as an intravenous (IV) infusion over 60 minutes ±5 minutes on an outpatient basis. | 2 |
| PF-06664178 0.30 mg/kg Participants were enrolled in cohorts of 2-4 to receive PF-06664178 in an open-label, unblinded manner and treated with PF-06664178 in 7 sequential dose levels between 0.15 and 4.8 mg/kg. PF-06664178 0.30 mg/kg was administered on Day 1 of each 21-day cycle per the DAI as an IV infusion over 60 minutes ±5 minutes on an outpatient basis. | 2 |
| PF-06664178 0.60 mg/kg Participants were enrolled in cohorts of 2-4 to receive PF-06664178 in an open-label, unblinded manner and treated with PF-06664178 in 7 sequential dose levels between 0.15 and 4.8 mg/kg. PF-06664178 0.60 mg/kg was administered on Day 1 of each 21-day cycle per the DAI as an IV infusion over 60 minutes ±5 minutes on an outpatient basis. | 4 |
| PF-06664178 1.20 mg/kg Participants were enrolled in cohorts of 2-4 to receive PF-06664178 in an open-label, unblinded manner and treated with PF-06664178 in 7 sequential dose levels between 0.15 and 4.8 mg/kg. PF-06664178 1.20 mg/kg was administered on Day 1 of each 21-day cycle per the DAI as an IV infusion over 60 minutes ±5 minutes on an outpatient basis. | 4 |
| PF-06664178 2.40 mg/kg Participants were enrolled in cohorts of 2-4 to receive PF-06664178 in an open-label, unblinded manner and treated with PF-06664178 in 7 sequential dose levels between 0.15 and 4.8 mg/kg. PF-06664178 2.40 mg/kg was administered on Day 1 of each 21-day cycle per the DAI as an IV infusion over 60 minutes ±5 minutes on an outpatient basis. | 4 |
| PF-06664178 3.60 mg/kg Participants were enrolled in cohorts of 2-4 to receive PF-06664178 in an open-label, unblinded manner and treated with PF-06664178 in 7 sequential dose levels between 0.15 and 4.8 mg/kg. PF-06664178 3.60 mg/kg was administered on Day 1 of each 21-day cycle per the DAI as an IV infusion over 60 minutes ±5 minutes on an outpatient basis. | 6 |
| PF-06664178 4.20 mg/kg Participants were enrolled in cohorts of 2-4 to receive PF-06664178 in an open-label, unblinded manner and treated with PF-06664178 in 7 sequential dose levels between 0.15 and 4.8 mg/kg. PF-06664178 4.20 mg/kg was administered on Day 1 of each 21-day cycle per the DAI as an IV infusion over 60 minutes ±5 minutes on an outpatient basis. | 1 |
| PF-06664178 4.80 mg/kg Participants were enrolled in cohorts of 2-4 to receive PF-06664178 in an open-label, unblinded manner and treated with PF-06664178 in 7 sequential dose levels between 0.15 and 4.8 mg/kg. PF-06664178 4.80 mg/kg was administered on Day 1 of each 21-day cycle per the DAI as an IV infusion over 60 minutes ±5 minutes on an outpatient basis. | 8 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Part 1: Dose Escalation | Death | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Dose Escalation | Lost to Follow-up | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 |
| Part 1: Dose Escalation | Other | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 2 |
| Part 1: Dose Escalation | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | PF-06664178 0.15 mg/kg | PF-06664178 0.30 mg/kg | PF-06664178 0.60 mg/kg | PF-06664178 1.20 mg/kg | PF-06664178 2.40 mg/kg | PF-06664178 3.60 mg/kg | PF-06664178 4.20 mg/kg | PF-06664178 4.80 mg/kg | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 54 years STANDARD_DEVIATION 7.1 | 75 years STANDARD_DEVIATION 11.3 | 61 years STANDARD_DEVIATION 17.9 | 52.8 years STANDARD_DEVIATION 20 | 46 years STANDARD_DEVIATION 11 | 53.7 years STANDARD_DEVIATION 11.8 | 63 years STANDARD_DEVIATION 0 | 61.1 years STANDARD_DEVIATION 6.6 | 57.1 years STANDARD_DEVIATION 13.2 |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 5 Participants | 1 Participants | 6 Participants | 18 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 1 Participants | 0 Participants | 2 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 2 | 2 / 2 | 4 / 4 | 4 / 4 | 4 / 4 | 6 / 6 | 1 / 1 | 8 / 8 | 31 / 31 |
| serious Total, serious adverse events | 0 / 2 | 1 / 2 | 2 / 4 | 0 / 4 | 1 / 4 | 3 / 6 | 1 / 1 | 5 / 8 | 13 / 31 |
Outcome results
Primary
First Cycle Dose Limiting Toxicities (DLTs) In Order to Determine the Maximum Tolerated Dose(MTD)
Number of participants that experienced dose limiting toxicities(DLTs) at given dose level.
Time frame: Day 1 up to Day 21
Population: All enrolled participants who started treatment. One of participants that experienced DLTs in PF-06664178 4.80mg/kg group was a late DLT that occurred at the beginning of Cycle 2 and was classified as a late DLT.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-06664178 0.15 mg/kg | First Cycle Dose Limiting Toxicities (DLTs) In Order to Determine the Maximum Tolerated Dose(MTD) | Yes | 0 participants |
| PF-06664178 0.15 mg/kg | First Cycle Dose Limiting Toxicities (DLTs) In Order to Determine the Maximum Tolerated Dose(MTD) | No | 2 participants |
| PF-06664178 0.30 mg/kg | First Cycle Dose Limiting Toxicities (DLTs) In Order to Determine the Maximum Tolerated Dose(MTD) | Yes | 0 participants |
| PF-06664178 0.30 mg/kg | First Cycle Dose Limiting Toxicities (DLTs) In Order to Determine the Maximum Tolerated Dose(MTD) | No | 2 participants |
| PF-06664178 0.60 mg/kg | First Cycle Dose Limiting Toxicities (DLTs) In Order to Determine the Maximum Tolerated Dose(MTD) | Yes | 0 participants |
| PF-06664178 0.60 mg/kg | First Cycle Dose Limiting Toxicities (DLTs) In Order to Determine the Maximum Tolerated Dose(MTD) | No | 4 participants |
| PF-06664178 1.20 mg/kg | First Cycle Dose Limiting Toxicities (DLTs) In Order to Determine the Maximum Tolerated Dose(MTD) | Yes | 0 participants |
| PF-06664178 1.20 mg/kg | First Cycle Dose Limiting Toxicities (DLTs) In Order to Determine the Maximum Tolerated Dose(MTD) | No | 4 participants |
| PF-06664178 2.40 mg/kg | First Cycle Dose Limiting Toxicities (DLTs) In Order to Determine the Maximum Tolerated Dose(MTD) | Yes | 0 participants |
| PF-06664178 2.40 mg/kg | First Cycle Dose Limiting Toxicities (DLTs) In Order to Determine the Maximum Tolerated Dose(MTD) | No | 4 participants |
| PF-06664178 3.60 mg/kg | First Cycle Dose Limiting Toxicities (DLTs) In Order to Determine the Maximum Tolerated Dose(MTD) | Yes | 2 participants |
| PF-06664178 3.60 mg/kg | First Cycle Dose Limiting Toxicities (DLTs) In Order to Determine the Maximum Tolerated Dose(MTD) | No | 4 participants |
| PF-06664178 4.20 mg/kg | First Cycle Dose Limiting Toxicities (DLTs) In Order to Determine the Maximum Tolerated Dose(MTD) | No | 0 participants |
| PF-06664178 4.20 mg/kg | First Cycle Dose Limiting Toxicities (DLTs) In Order to Determine the Maximum Tolerated Dose(MTD) | Yes | 1 participants |
| PF-06664178 4.80 mg/kg | First Cycle Dose Limiting Toxicities (DLTs) In Order to Determine the Maximum Tolerated Dose(MTD) | Yes | 4 participants |
| PF-06664178 4.80 mg/kg | First Cycle Dose Limiting Toxicities (DLTs) In Order to Determine the Maximum Tolerated Dose(MTD) | No | 4 participants |
Primary
Number of Participants With Laboratory Abnormalities [Part 2 & 3]
Number of participants with a laboratory abnormality meeting specified criteria. The laboratory test included: hematology( hemoglobin, platelets, white blood cell count, absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils, absolute basophils), chemistry (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen or urea, creatinine, uric acid, glucose, albumin, phosphorous or phosphate), coagulation (prothrombin time or International normalized ratio, partial thromboplastin time), Urinalysis (urine protein, urine blood) and pregnancy test.
Time frame: On Day1, Day4, Day8, Day15 of the first cycle; on Day1, Day8, Day15 of the second cycle; on Day 1 of the subsequent cycles; end of treatment visit(no longer than 1 week after the patient has been discontinued)
Population: No participant was analyzed due to study termination
Primary
Number of Patients With All-Causality Treatment-Emergent Adverse Events(TEAEs) [Part 2 & 3]
An adverse event (AE) was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug.
Time frame: Day 1 up to Day 21
Population: No participant was analyzed due to study termination
Secondary
Accumulation Ratio (Rac) of PF-06664178 [Part 1 ,2 & 3]
Accumulation ratio refers to AUCtau for cycle 4/AUCtau for cycle 1, where AUCtau is defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to the time tau, the dosing interval.
Time frame: 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment
Population: Data were not collected during Part 1, and no participant was analyzed in Part 2 and 3 due to study termination
Secondary
Accumulation Ratio (Rac) of Total Antibody (PF-06479118) [Part 1 ,2 & 3]
Accumulation ratio refers to AUCtau for cycle 4/AUCtau for cycle 1, where AUCtau is defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to the time tau, the dosing interval.
Time frame: 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment
Population: Data were not collected during Part 1, and no participant was analyzed in Part 2 and 3 due to study termination
Secondary
Accumulation Ratio (Rac) of Unconjugated Payload (PF-06380101) [Part 1 ,2 & 3]
Accumulation ratio refers to AUCtau for cycle 4/AUCtau for cycle 1, where AUCtau is defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to the time tau, the dosing interval.
Time frame: 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment
Population: Data were not collected during Part 1, and no participant was analyzed in Part 2 and 3 due to study termination
Secondary
Area Under the Concentration-Time Curve Over the Dosing Interval(AUCtau) of PF-06664178 [Part 1 ,2 & 3]
AUCtau refers to area under the concentration-time profile from time zero to the time tau, the dosing interval
Time frame: 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment
Population: Data were not collected during Part 1, and no participant was analyzed in Part 2 and 3 due to study termination
Secondary
Area Under the Concentration-Time Curve Over the Dosing Interval(AUCtau) of Total Antibody(PF-06479118) [Part 1 ,2 & 3]
AUCtau refers to area under the concentration-time profile from time zero to the time tau, the dosing interval.
Time frame: 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment
Population: Data were not collected during Part 1, and no participant was analyzed in Part 2 and 3 due to study termination
Secondary
Area Under the Concentration-Time Curve Over the Dosing Interval(AUCtau) of Unconjugated Payload(PF-06380101) [Part 1 ,2 & 3]
AUCtau refers to area under the concentration-time profile from time zero to the time tau, the dosing interval.
Time frame: 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment
Population: Data were not collected during Part 1, and no participant was analyzed in Part 2 and 3 due to study termination
Secondary
Maximum Observed Plasma Concentration (Cmax) for PF-06664178 [Part 1 ,2 & 3]
Cmax of PF-06664178 was observed directly from data
Time frame: 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment
Population: Data were not collected during Part 1, and no participant was analyzed in Part 2 and 3 due to study termination
Secondary
Maximum Observed Plasma Concentration (Cmax) for Total Antibody (PF-06479118) [Part 1 ,2 & 3]
Cmax of total antibody PF-06479118 was observed directly from data
Time frame: 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment
Population: Data were not collected during Part 1, and no participant was analyzed in Part 2 and 3 due to study termination
Secondary
Maximum Observed Plasma Concentration (Cmax) for Unconjugated Payload (PF-06380101) [Part 1 ,2 & 3]
Cmax of unconjugated payload PF-06380101 was observed directly from data
Time frame: 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment
Population: Data were not collected during Part 1, and no participant was analyzed in Part 2 and 3 due to study termination
Secondary
Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs ) [Part 1]
An adverse event (AE) was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug.
Time frame: From screening up to 28 days after the last treatment administration in each cycle, and follow-up visits(At least 28 days and no more than 35 days after discontinuation of treatment)
Population: All enrolled participants who started treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-06664178 0.15 mg/kg | Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs ) [Part 1] | 2 participants |
| PF-06664178 0.30 mg/kg | Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs ) [Part 1] | 2 participants |
| PF-06664178 0.60 mg/kg | Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs ) [Part 1] | 4 participants |
| PF-06664178 1.20 mg/kg | Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs ) [Part 1] | 4 participants |
| PF-06664178 2.40 mg/kg | Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs ) [Part 1] | 4 participants |
| PF-06664178 3.60 mg/kg | Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs ) [Part 1] | 6 participants |
| PF-06664178 4.20 mg/kg | Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs ) [Part 1] | 1 participants |
| PF-06664178 4.80 mg/kg | Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs ) [Part 1] | 8 participants |
Secondary
Number of Participants With Laboratory Abnormalities[Part 1]
Number of participants with a laboratory abnormality meeting specified criteria. The laboratory test included: hematology( hemoglobin, platelets, white blood cell count, absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils, absolute basophils), chemistry (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen or urea, creatinine, uric acid, glucose, albumin, phosphorous or phosphate), coagulation (prothrombin time or International normalized ratio, partial thromboplastin time), Urinalysis (urine protein, urine blood) and pregnancy test.
Time frame: Screening; on Day1, Day4, Day8, Day15 of the first cycle; on Day1, Day8, Day15 of the second cycle; on Day 1 of the subsequent cycles; end of treatment visit(no longer than 1 week after the patient has been discontinued)
Population: All enrolled participants who started treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-06664178 0.15 mg/kg | Number of Participants With Laboratory Abnormalities[Part 1] | 1 participants |
| PF-06664178 0.30 mg/kg | Number of Participants With Laboratory Abnormalities[Part 1] | 2 participants |
| PF-06664178 0.60 mg/kg | Number of Participants With Laboratory Abnormalities[Part 1] | 4 participants |
| PF-06664178 1.20 mg/kg | Number of Participants With Laboratory Abnormalities[Part 1] | 4 participants |
| PF-06664178 2.40 mg/kg | Number of Participants With Laboratory Abnormalities[Part 1] | 4 participants |
| PF-06664178 3.60 mg/kg | Number of Participants With Laboratory Abnormalities[Part 1] | 6 participants |
| PF-06664178 4.20 mg/kg | Number of Participants With Laboratory Abnormalities[Part 1] | 0 participants |
| PF-06664178 4.80 mg/kg | Number of Participants With Laboratory Abnormalities[Part 1] | 8 participants |
Secondary
Overall Incidence of Anti-PF-06664178-Antibodies[Part 1]
Number of participants with the presence of anti-PF-06664178 antibodies
Time frame: Day 1, 15, 21, and every 21 days thereafter up to 24 months, and end of treatment
Population: All enrolled participants who started treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-06664178 0.15 mg/kg | Overall Incidence of Anti-PF-06664178-Antibodies[Part 1] | 2 participants |
| PF-06664178 0.30 mg/kg | Overall Incidence of Anti-PF-06664178-Antibodies[Part 1] | 2 participants |
| PF-06664178 0.60 mg/kg | Overall Incidence of Anti-PF-06664178-Antibodies[Part 1] | 4 participants |
| PF-06664178 1.20 mg/kg | Overall Incidence of Anti-PF-06664178-Antibodies[Part 1] | 4 participants |
| PF-06664178 2.40 mg/kg | Overall Incidence of Anti-PF-06664178-Antibodies[Part 1] | 4 participants |
| PF-06664178 3.60 mg/kg | Overall Incidence of Anti-PF-06664178-Antibodies[Part 1] | 6 participants |
| PF-06664178 4.20 mg/kg | Overall Incidence of Anti-PF-06664178-Antibodies[Part 1] | 0 participants |
| PF-06664178 4.80 mg/kg | Overall Incidence of Anti-PF-06664178-Antibodies[Part 1] | 8 participants |
Secondary
Overall Incidence of Anti-PF-06664178-Antibodies [Part 2 & 3]
Number of participants with the presence of anti-PF-06664178 antibodies
Time frame: Day 1, 15, 21, and every 21 days thereafter up to 24 months, and end of treatment
Population: No participant was analyzed due to study termination
Secondary
Overall Number of Participants With Objective Tumor Response[Part 1]
Objective tumor response, was assessed using the Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 by calculating the Overall Response Rate, and Prolonged Stable Disease. The criterion is defined as: Objective Progression(PD):20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5mm; Stable (SD): All target lesions must be assessed. Stable can follow PR only in the rare case that the sum increases by less than 20% from the nadir, but enough that a previously documented 30% decrease no longer holds; symptomatic deterioration(Sym):Participants with a global deterioration of health status requiring discontinuation of treatment without objective evidence of disease progression at that time; Indeterminate (In):Progression has not been determined and one, or more non-target sites were not assessed, or assessment methods were inconsistent with those used at baseline.
Time frame: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months
Population: Of all enrolled 31 patients who were treated, 1 participant from the 0.60mg/kg cohort and 1 participant from the 4.20mg/kg cohort did not have post-dose tumor evaluations for they were discontinued form study prior to having disease assessment .
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-06664178 0.15 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | SD | 0 participants |
| PF-06664178 0.15 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | PD | 2 participants |
| PF-06664178 0.15 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | Sym | 0 participants |
| PF-06664178 0.15 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | In | 0 participants |
| PF-06664178 0.30 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | In | 0 participants |
| PF-06664178 0.30 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | Sym | 0 participants |
| PF-06664178 0.30 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | SD | 1 participants |
| PF-06664178 0.30 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | PD | 1 participants |
| PF-06664178 0.60 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | Sym | 0 participants |
| PF-06664178 0.60 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | PD | 2 participants |
| PF-06664178 0.60 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | SD | 1 participants |
| PF-06664178 0.60 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | In | 0 participants |
| PF-06664178 1.20 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | SD | 1 participants |
| PF-06664178 1.20 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | PD | 3 participants |
| PF-06664178 1.20 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | Sym | 0 participants |
| PF-06664178 1.20 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | In | 0 participants |
| PF-06664178 2.40 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | SD | 2 participants |
| PF-06664178 2.40 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | In | 0 participants |
| PF-06664178 2.40 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | PD | 2 participants |
| PF-06664178 2.40 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | Sym | 0 participants |
| PF-06664178 3.60 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | PD | 1 participants |
| PF-06664178 3.60 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | SD | 4 participants |
| PF-06664178 3.60 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | Sym | 1 participants |
| PF-06664178 3.60 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | In | 0 participants |
| PF-06664178 4.80 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | Sym | 0 participants |
| PF-06664178 4.80 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | SD | 2 participants |
| PF-06664178 4.80 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | PD | 3 participants |
| PF-06664178 4.80 mg/kg | Overall Number of Participants With Objective Tumor Response[Part 1] | In | 3 participants |
Secondary
Overall Number of Participants With Objective Tumor Response [Part 2 & 3]
Objective tumor response, as assessed using the Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 by calculating the Overall Response Rate (ORR), and Prolonged Stable Disease (SD).No Progression Free Survival (PFS) was completed. The criterion is as follow: Objective Progression(PD), Stable (SD), symptomatic deterioration(Sym), and Indeterminate (In)
Time frame: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months
Population: No participant was analyzed due to study termination
Secondary
Systemic Clearance (CL) of PF-06664178 [Part 1 ,2 & 3]
CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Time frame: 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment
Population: Data were not collected during Part 1, and no participant was analyzed in Part 2 and 3 due to study termination
Secondary
Systemic Clearance (CL) of Total Antibody (PF-06479118) [Part 1 ,2 & 3]
CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Time frame: 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment
Population: Data were not collected during Part 1, and no participant was analyzed in Part 2 and 3 due to study termination
Secondary
Systemic Clearance (CL) of Unconjugated Payload (PF-06380101) [Part 1 ,2 & 3]
CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Time frame: 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment
Population: Data were not collected during Part 1, and no participant was analyzed in Part 2 and 3 due to study termination
Secondary
Terminal Elimination Half-Life (t1/2) of PF-06664178 [Part 1 ,2 & 3]
Terminal elimination half-life is the time measured for the plasma concentration to decrease by one half
Time frame: 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment
Population: Data were not collected during Part 1, and no participant was analyzed in Part 2 and 3 due to study termination
Secondary
Terminal Elimination Half-Life (t1/2) of Total Antibody (PF-06479118)[Part 1 ,2 & 3]
Terminal elimination half-life is the time measured for the plasma concentration to decrease by one half
Time frame: 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment
Population: Data were not collected during Part 1, and no participant was analyzed in Part 2 and 3 due to study termination
Secondary
Terminal Elimination Half-Life (t1/2) of Unconjugated Payload (PF-06380101) [Part 1 ,2 & 3]
Terminal elimination half-life is the time measured for the plasma concentration to decrease by one half
Time frame: 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment
Population: Data were not collected during Part 1, and no participant was analyzed in Part 2 and 3 due to study termination
Secondary
Trop-2 Expression Levels on Archived Tissue [Part 2 & 3]
Number of participents meeting the following criterion for Trop-2 expression assessment : low expression, medium expression and high expression
Time frame: Day 1
Population: No participant was analyzed due to study termination
Secondary
Volume of Distribution (Vss) of PF-06664178 [Part 1 ,2 & 3]
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.
Time frame: 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment
Population: Data were not collected during Part 1, and no participant was analyzed in Part 2 and 3 due to study termination
Secondary
Volume of Distribution (Vss) of Total Antibody (PF-06479118) [Part 1 ,2 & 3]
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.
Time frame: 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment
Population: Data were not collected during Part 1, and no participant was analyzed in Part 2 and 3 due to study termination
Secondary
Volume of Distribution (Vss) of Unconjugated Payload (PF-06380101) [Part 1 ,2 & 3]
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.
Time frame: 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment
Population: Data were not collected during Part 1, and no participant was analyzed in Part 2 and 3 due to study termination