A Study Of PF-06664178 In Patients With Advanced Solid Tumors

Study Overview
=================
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.

Official Title
-----------------
A Phase 1, Dose Escalation Study Of Pf-06664178 In Patients With Locally Advanced Or Metastatic Solid Tumors

Conditions
-----------------
Neoplasms

Intervention / Treatment
-----------------
* Drug: PF-06664178
* Drug: PF-06664178


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-06664178<br>Experimental | Drug: PF-06664178<br>* 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.<br>Drug: PF-06664178<br>* Part 2 - patients with select tumor types (Non Small Cell Lung Cancer ovarian cancer, and breast cancer ) will be treated at the MTD selected in Part 1.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 1 up to Day 21 | 
| 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. | Day 1 up to Day 21 | 
| 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. | 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) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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) | 
| 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. | 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) | 
| Overall Incidence of Anti-PF-06664178-Antibodies[Part 1] | Number of participants with the presence of anti-PF-06664178 antibodies | Day 1, 15, 21, and every 21 days thereafter up to 24 months, and end of treatment | 
| Overall Incidence of Anti-PF-06664178-Antibodies [Part 2 & 3] | Number of participants with the presence of anti-PF-06664178 antibodies | Day 1, 15, 21, and every 21 days thereafter up to 24 months, and end of treatment | 
| 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. | Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months | 
| 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) | Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months | 
| Maximum Observed Plasma Concentration (Cmax) for PF-06664178 [Part 1 ,2 & 3] | Cmax of PF-06664178 was observed directly from data | 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 | 
| 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 | 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 | 
| 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 | 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 | 
| 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 | 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 | 
| 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. | 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 | 
| 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. | 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 | 
| 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. | 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 | 
| 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. | 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 | 
| 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. | 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 (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. | 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 (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. | 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 (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. | 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 (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 | 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 (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 | 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 (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 | 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 | 
| 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 | Day 1 | 
| 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. | 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 (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. | 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 (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. | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ADC, PF-06664178, solid tumors, tumors, neoplasm metastasis, NSCLC, non small cell lung cancer, OVCA, ovarian cancer, Phase 1, breast cancer