A Dose Escalation Study Of PF-06939999 In Participants With Advanced Or Metastatic Solid Tumors
- Conditions
- Metastatic Solid TumorsAdvanced Solid Tumors
- Interventions
- Drug: PF-06939999 dose escalationDrug: PF-06939999 monotherapy
- Registration Number
- NCT03854227
- Lead Sponsor
- Pfizer
- Brief Summary
This is a Phase 1, open label, multi center, dose escalation and expansion, safety, tolerability, PK, and pharmacodynamics study of PF 06939999 in previously treated patients with advanced or metastatic cancer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 54
- Histologically or cytologically confirmed locally advanced or metastatic NSCLC, urothelial carcinoma or HNSCC
- Progressed after at least 1 line of treatment and no more than 3 lines of treatment
- At least one measurable lesion as defined by RECIST version 1.1
- ECOG Performance Status 0 or 1
- Adequate Bone Marrow Function
- Adequate Renal Function
- Adequate Liver Function
- Resolved acute effects of any prior therapy
- Known active uncontrolled or symptomatic CNS metastases.
- Major surgery, radiation therapy, systemic anti-cancer therapy or investigational drug(s) within 4 weeks prior to study entry.
- Active, uncontrolled infection, including COVID-19
- Known or suspected hypersensitivity to PF-06939999
- Inability to consume or absorb study drug
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dose Escalation PF-06939999 dose escalation Participants will receive PF-06939999 orally at escalating doses in 28 day cycles on a continuous basis Non small cell lung cancer monotherapy PF-06939999 monotherapy Participants will receive PF-06939999 at the recommended Phase 2 dose in 28 day cycles on a continuous basis Urothelial carcinoma PF-06939999 monotherapy Participants will receive PF-06939999 at the recommended Phase 2 dose in 28 day cycles on a continuous basis Head and neck squamous cell carcinoma PF-06939999 monotherapy Participants will receive PF-06939999 at the recommended Phase 2 dose in 28 day cycles on a continuous basis Non small cell lung cancer PF-06939999 plus docetaxel PF-06939999 in combination with docetaxel Participants will receive PF-06939999 on a continuous basis in combination with docetaxel Non small cell lung cancer dose finding PF-06939999 in combination with docetaxel Participants will receive PF-06939999 on a continuous basis at escalating doses in combination with docetaxel
- Primary Outcome Measures
Name Time Method Part 1A: Number of Participants With Dose-Limiting Toxicities (DLT) Baseline through day 29. DLTs=any of the following adverse events (AEs) occurring in the DLT observation period (first treatment cycle):1) Any Grade 4 hematologic AEs; Grade 4 neutropenia, febrile neutropenia, Grade 3 neutropenia with infection, Grade 3 thrombocytopenia with ≥Grade 2 clinically significant bleeding, Grade 3 anemia requiring blood transfusion; 2) Any Grade ≥3 non-hematologic AEs; Grade 3 nausea/vomiting or diarrhea lasting ≥4 days after treatment, confirmed drug induced liver injury meeting Hy's law criteria; a hepatic transaminase or alkaline phosphatase level \>10 times the upper limit of normal for participants with Grade 2 hepatic transaminase or alkaline phosphatase levels at baseline as a result of liver/bone metastasis; clinically important or persistent toxicities; 3) Any toxicity causing \>2 weeks of dose delay; 4) any dose reduction due to AE during the first cycle. Grades of AEs were defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.
Part 1A: Number of Participants With Treatment-Emergent Adverse Events (TEAE) Baseline up to a minimum of 28 days after last dose of study treatment (maximum of 13 months) An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Grades of AEs were defined by NCI CTCAE version 5.0. Grade 3 events = unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 events = events that caused participant to be in imminent danger of death. Grade 5 events = death related to an AE.
Part 1A: Number of Participants With Laboratory Abnormalities Baseline up to a minimum of 28 days after last dose of study treatment (maximum of 12 months) Laboratory assessments included hematology, chemistry and urinary tests. Participants with maximum Grade 3-4 laboratory abnormalities are reported in this OM. Grades of laboratory results were defined by NCI CTCAE version 5.0. Grade 3 events = unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 events = events that caused participant to be in imminent danger of death. Some of the Grade 4 events (activated partial thromboplastin time prolonged, anemia, hemoglobin increased, leukocytosis, lymphocyte count increased and hypoalbuminemia) could not be defined/determined based only on lab data, therefore are not reported in this OM.
Part 2: Number of Participants With TEAEs Baseline up to a minimum of 28 days after last dose of study treatment (maximum of 15 months) An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Grades of AEs were defined by NCI CTCAE version 5.0. Grade 3 events = unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 events = events that caused participant to be in imminent danger of death. Grade 5 events = death related to an AE.
Part 2: Number of Participants With Laboratory Abnormalities Baseline up to a minimum of 28 days after last dose of study treatment (maximum of 8 months) Laboratory assessments included hematology, chemistry and urinary tests. Participants with maximum Grade 3-4 laboratory abnormalities are reported in this OM. Grades of laboratory results were defined by NCI CTCAE version 5.0. Grade 3 events = unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 events = events that caused participant to be in imminent danger of death. Some of the Grade 4 events (activated partial thromboplastin time prolonged, anemia, hemoglobin increased, leukocytosis, lymphocyte count increased and hypoalbuminemia) could not be defined/determined based only on lab data, therefore are not reported in this OM.
Part 2: Number of Participants With Best Overall Response (BOR) Based on Investigator Assessment (RECIST, Version 1.1) From baseline up to 28 ~ 35 days after end of treatment (maximum of 6 months). Number of participants with BOR assessed using Response Evaluation Criteria in Solid Tumor (RECIST) v1.1: Complete Response (CR): disappearance of all lesions (with the exception of nodal disease when assessing target lesions). Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered a sign of progression. Stable disease (SD): does not qualify for CR, PR or PD. Non-CR/Non-PD: Persistence of any non target lesions and/or tumor marker level above the normal limits.
- Secondary Outcome Measures
Name Time Method Part 2B: PK Parameters of PF-06939999 Given With and Without Food - Tmax Predose and 0.5, 1, 2, 4, 6 and 12 hours post dose on Cycle 1 Day 15 (fasted condition); predose and 0.5, 1, 2, 4, 6 and 12 hours post dose on Cycle 1 Day 16 (with food). Time to maximum plasma concentration of PF-06939999 given with and without food. On Cycle 1 Day 15, participants enrolled in the food-effect substudy of Part 2B received an oral dose of PF-06939999 under the fasted condition (overnight fasting of at least 10 hours; water permitted). On Cycle 1 Day 16, these participants received another oral dose of PF-06939999 with a high-fat, high-calorie meal (breakfast) following 10-hour overnight fasting (water permitted).
Part 1A: PK Parameters of PF-06939999: Single Dose (SD) - Maximum Observed Plasma Concentration (Cmax) Pre-dose and 0.5 hour, 1 hour, 2 hours, 4 hours, 6 hours and 12 hours post the morning dose on Cycle 1 Day 1. Maximum plasma concentration of PF-06939999 after the participant received a SD on Cycle 1 Day 1. Cmax was directly observed from data.
Part 1A: PK Parameters of PF-06939999: SD - Time to Reach Maximum Observed Plasma Concentration (Tmax) Predose, 0.5, 1, 2, 4, 6 and 12 hours post the morning dose on Cycle 1 Day 1. Time to maximum plasma concentration of PF-06939999 after the participant received a SD on Cycle 1 Day 1. Tmax was observed directly from data.
Part 1A: PK Parameters of PF-06939999: SD - Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Predose, 0.5, 1, 2, 4, 6 and 12 hours post the morning dose on Cycle 1 Day 1. Area under the plasma concentration versus time curve (AUC) from time 0 to the last measured concentration (AUClast) after the participant received a SD of PF-06939999 on Cycle 1 Day 1.
Part 1A: PK Parameters of PF-06939999: Multiple Dose (MD) - Steady State Maximum Observed Plasma Concentration (Cmax,ss) Predose, 0.5, 1, 2, 4, 6 and 12 hours post the morning dose on Cycle 1 Day 15. Cmax,ss was the steady-state maximum concentration of PF-06939999 after MD. Cmax,ss was observed directly from the data.
Part 1A: PK Parameters of PF-06939999: MD - Steady State Time to Reach Maximum Observed Plasma Concentration (Tmax,ss) Predose, 0.5, 1, 2, 4, 6 and 12 hours post the morning dose on Cycle 1 Day 15. Tmax,ss was the steady-state time to maximum plasma concentration of PF-06939999 after MD. Tmax,ss was observed directly from data.
Part 1A: PK Parameters of PF-06939999: MD - Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau,ss) Predose, 0.5, 1, 2, 4, 6 and 12 hours post the morning dose on Cycle 1 Day 15. AUCtau,ss was the steady-state area under the concentration-time profile from time zero to time tau (τ) of PF-06939999 after MD.
Part 1A: PK Parameters of PF-06939999: MD - Apparent Oral Clearance (CL/F) Predose, 0.5, 1, 2, 4, 6 and 12 hours post the morning dose on Cycle 1 Day 15. Apparent oral plasma clearance of PF-06939999 after MD. CL/F after multiple doses = Dose/AUCtau,ss. AUCtau,ss = area under the concentration-time profile from time zero to time tau after multiple doses.
Part 1A: PK Parameters of PF-06939999: MD - Accumulation Ratio (Rac) Pre-dose and 0.5 hour, 1 hour, 2 hours, 4 hours, 6 hours and 12 hours post the morning dose on Cycle 1 Day 1; Pre-dose and 0.5, 1, 2, 4, 6 and 12 hours post the morning dose on Cycle 1 Day 15. Rac was observed accumulation ratio based on AUCtau. Rac was calculated as AUCtau (multiple dose, Cycle 1 Day 15)/ AUCtau (single dose, Cycle 1 Day 1). AUCtau was area under the concentration-time profile from time zero to time tau (τ), the dosing interval.
Part 2: PK Parameters of PF-06939999: SD - Cmax Pre-dose and 0.5 hour, 1 hour, 2 hours and 4 hours post Cycle 1 Day 1 dosing. Maximum plasma concentration of PF-06939999 after the participant received a SD on Cycle 1 Day 1. Cmax was directly observed from data.
Part 2: PK Parameters of PF-06939999: SD - Tmax Pre-dose and 0.5 hour, 1 hour, 2 hours and 4 hours post Cycle 1 Day 1 dosing. Time to maximum plasma concentration of PF-06939999 after the participant received a SD on Cycle 1 Day 1. Tmax was observed directly from data.
Part 2: PK Parameters of PF-06939999: MD - Cmax,ss Pre-dose and 0.5 hour, 1 hour, 2 hours and 4 hours post Cycle 1 Day 15 dosing. Cmax,ss was the steady-state maximum concentration of PF-06939999 after MD. Cmax,ss was observed directly from the data.
Part 2: PK Parameters of PF-06939999: MD - Tmax,ss Pre-dose and 0.5 hour, 1 hour, 2 hours and 4 hours post Cycle 1 Day 15 dosing. Tmax,ss was the steady-state time to maximum plasma concentration of PF-06939999 after MD. Tmax,ss was observed directly from data.
Part 2: PK Parameters of PF-06939999: MD - Trough Concentration (Ctrough). Pre-dose and 0.5 hour, 1 hour, 2 hours and 4 hours post Cycle 1 Day 15 dosing. Ctrough was trough serum concentration of PF-06939999 after MD. Ctrough = Cmin.
Part 2B: PK Parameters of PF-06939999 Given With and Without Food - Cmax Predose and 0.5, 1, 2, 4, 6 and 12 hours post dose on Cycle 1 Day 15 (fasted condition); predose and 0.5, 1, 2, 4, 6 and 12 hours post dose on Cycle 1 Day 16 (with food). Maximum concentration of PF-06939999 given with and without food. On Cycle 1 Day 15, participants enrolled in the food-effect substudy of Part 2B received an oral dose of PF-06939999 under the fasted condition (overnight fasting of at least 10 hours; water permitted). On Cycle 1 Day 16, these participants received another oral dose of PF-06939999 with a high-fat, high-calorie meal (breakfast) following 10-hour overnight fasting (water permitted).
Part 2B: PK Parameters of PF-06939999 Given With and Without Food - AUClast Predose and 0.5, 1, 2, 4, 6 and 12 hours post dose on Cycle 1 Day 15 (fasted condition); predose and 0.5, 1, 2, 4, 6 and 12 hours post dose on Cycle 1 Day 16 (with food). AUClast of PF-06939999 given with and without food. On Cycle 1 Day 15, participants enrolled in the food-effect substudy of Part 2B received an oral dose of PF-06939999 under the fasted condition (overnight fasting of at least 10 hours; water permitted). On Cycle 1 Day 16, these participants received another oral dose of PF-06939999 with a high-fat, high-calorie meal (breakfast) following 10-hour overnight fasting (water permitted).
Part 1A: Percentage of Participants With Objective Response Based on Investigator Assessment (RECIST v1.1) From baseline up to 28 ~ 35 days after end of treatment (maximum of 12 months). Objective Response Rate (ORR) was defined as the percentage of participants who achieved CR or PR per RECIST 1.1. CR was defined as disappearance of all lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Part 1A: Duration of Response Based on Investigator Assessment (RECIST, v1.1) From baseline up to 28 ~ 35 days after end of treatment (maximum of 12 months). Duration of response was defined as the time from start date (which is the date of first documentation of PR or CR) to date of first documentation of objective progression or death. DOR was only applicable to those participants with an objective response (confirmed CR or PR). CR: disappearance of all lesions (with the exception of nodal disease when assessing target lesions). PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Part 2: Duration of Response Based on Investigator Assessment (RECIST, v1.1) From baseline up to 28 ~ 35 days after end of treatment (maximum of 6 months). Duration of response was defined as the time from start date (which is the date of first documentation of PR or CR) to date of first documentation of objective progression or death. DoR was only applicable to those participants with an objective response (confirmed CR or PR). CR: disappearance of all lesions (with the exception of nodal disease when assessing target lesions). PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Part 2: Progression Free Survival Based on Investigator Assessment (RECIST, v1.1) From baseline up to 28 ~ 35 days after end of treatment (maximum of 6 months). Progression Free Survival (PFS) was defined as the time from initiation of PF-06939999 therapy to first documentation of tumor progression or to death due to any cause, whichever occurred first.
Part 2: Time to Progression Based on Investigator Assessment (RECIST, v1.1) From baseline up to 28 ~ 35 days after end of treatment (maximum of 6 months). Time to Progression (TTP) was defined as the time from the date of the first treatment to the date of the first documentation of objective tumor progression or death due to tumor progression. Disease progression is defined using RECIST v 1.1.
Part 2: Overall Survival From baseline up to maximum follow up (15 months). Overall Survival (OS) was defined as the time from the start date (first dose) of study treatment to the date of death due to any cause.
Part 2: Probability of Survival at 6 Months and 1 Year of PF-06939999 Monotherapy From baseline up to maximum follow up (15 months). The probability of survival at select times was estimated using the Kaplan Meier method. Although an endpoint of Overall Survival at 2 years of study treatment was defined in the protocol, no data were collected/analyzed for this endpoint due to maximum follow up not reaching 2 year post study treatment.
Trial Locations
- Locations (22)
Scottsdale Healthcare Hospitals d/b/a HonorHealth
🇺🇸Scottsdale, Arizona, United States
Virginia G. Piper Cancer Pharmacy
🇺🇸Scottsdale, Arizona, United States
University Of Miami Hospital and Clinics/Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
AdventHealth Orlando - Investigational Drug Services
🇺🇸Orlando, Florida, United States
AdventHealth Orlando Infusion Center
🇺🇸Orlando, Florida, United States
Henry-Joyce Cancer Clinic
🇺🇸Nashville, Tennessee, United States
Keck Hospital of USC
🇺🇸Los Angeles, California, United States
LAC + USC Medical Center
🇺🇸Los Angeles, California, United States
USC Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
USC/Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
AdventHealth Celebration Infusion Center
🇺🇸Celebration, Florida, United States
St. Joseph Mercy Brighton
🇺🇸Brighton, Michigan, United States
The University of Texas
🇺🇸Houston, Texas, United States
NEXT Oncology
🇺🇸San Antonio, Texas, United States
Inova Schar Cancer Institute
🇺🇸Fairfax, Virginia, United States
Keck Medical Center of USC Pasadena
🇺🇸Pasadena, California, United States
AdventHealth Medical Group Oncology Research at Celebration
🇺🇸Celebration, Florida, United States
AdventHealth Orlando
🇺🇸Orlando, Florida, United States
St. Joseph Mercy Hospital
🇺🇸Ann Arbor, Michigan, United States
Oncology IDS Pharmacy
🇺🇸Nashville, Tennessee, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States