A Dose Escalation Study Of PF-06939999 In Participants With Advanced Or Metastatic Solid Tumors

Phase 1

Terminated

• Conditions: Metastatic Solid Tumors; Advanced Solid Tumors
• Interventions: Drug: PF-06939999 dose escalation; Drug: PF-06939999 monotherapy; Drug: PF-06939999 in combination with docetaxel

• 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

Study Timeline

• Study First Submitted: 2019-02-15
• Study First Submitted QC: 2019-02-22
• Study First Posted: 2019-02-26
• Study Start: 2019-03-14
• Primary Completion: 2022-04-27
• Study Completion: 2022-04-27
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-17
• Last Update Posted: 2022-11-22

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 54

Inclusion Criteria

• 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

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Exclusion Criteria

• 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

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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
Number of participants with dose limiting toxicities (DLTs)	Baseline through day 28	DLTs will be evaluated during the first cycle. The number of DLTs will be used to determine the maximum tolerated dose (MTD)
Number of participants with treatment emergent adverse events (AEs)	Baseline through up to 2 years or until disease progression	Adverse events as characterized by type, frequency, severity, timing, seriousness and relationship to study therapy
Number of participants with laboratory abnormalities	Baseline through up to 2 years or until disease progression	Laboratory abnormalities as characterized by type, frequency, severity, and timing.
Objective Response Rate	Baseline through up to 2 years or until disease progression	Best Overall Response by RECIST 1.1

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax)	Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24	Single dose PK will be calculated including Maximum Observed Plasma Concentration (Cmax).
Pharmacokinetic Parameters: Time to reach Maximum Observed Plasma Concentration (Tmax)	Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24	Single dose PK will be calculated including Time to reach Maximum Observed Plasma Concentration (Tmax).
Pharmacokinetic Parameters: Area Under the Curve from time 0 to the last sampling time point within the dose interval (AUClast)	Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24	Single dose PK will be calculated including Area Under the Curve from time 0 to the last sampling time point within the dose interval (AUClast)
Pharmacokinetic Parameters: Steady state apparent volume of distribution (Vss/F)	Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24	Multiple dose PK will be calculated including, as data permit, steady state apparent volume of distribution (Vss/F)
Overall Survival (OS)	Baseline through up to 2 years	Proportion of participants alive at 6 months, 1 year and 2 years.
Pharmacokinetic Parameters: Terminal elimination half life (t1/2)	Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24	Single dose PK will be calculated including, as data permit, terminal elimination half life (t1/2)
Pharmacokinetic Parameters: AUC from time 0 extrapolated to infinity (AUCinf)	Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24	Single dose PK will be calculated including, as data permit, Area Under the Curve from time 0 extrapolated to infinity (AUCinf)
Pharmacokinetic Parameters: Apparent oral plasma clearance (CL/F)	Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24	Single dose PK will be calculated including, as data permit, apparent oral plasma clearance (CL/F)
Pharmacokinetic Parameters: Apparent volume of distribution (Vz/F)	Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24	Single dose PK will be calculated including, as data permit, apparent volume of distribution (Vz/F)
Pharmacokinetic Parameters: Maximum Observed Steady State Plasma Concentration (Css,max)	Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24	Multiple dose PK will be calculated including Maximum Observed Steady State Plasma Concentration (Css,max).
Time to progression (TTP)	Baseline through up to 2 years or until disease progression	TTP as assessed using RECIST 1.1.
Pharmacokinetic Parameters: Time to reach Maximum Observed Steady State Plasma Concentration (Tss,max)	Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24	Multiple dose PK will be calculated including Time to reach Maximum Observed Steady State Plasma Concentration (Tss,max).
Progression free survival (PFS)	Baseline through up to 2 years or until disease progression	PFS as assessed using RECIST 1.1.
Pharmacokinetic Parameters: Area Under the Curve within one dose interval (AUCss,t)	Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24	Multiple dose PK will be calculated including Area Under the Curve within one dose interval (AUCss,t)
Pharmacokinetic Parameters: Steady state apparent oral plasma clearance (CL/F)	Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8. 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24	Multiple dose PK will be calculated including, as data permit, steady state apparent oral plasma clearance (CL/F)
Pharmacokinetic Parameters: Accumulation ratio (Rac)	Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24	Multiple dose PK will be calculated including, as data permit, accumulation ratio (Rac)
Duration of response (DOR)	Baseline through up to 2 years or until disease progression	DOR as assessed using RECIST 1.1

Trial Locations

Locations (22)

Scottsdale Healthcare Hospitals d/b/a HonorHealth; 🇺🇸 Scottsdale, Arizona, United States

Virginia G. Piper Cancer Pharmacy; 🇺🇸 Scottsdale, Arizona, United States

Keck Hospital of USC; 🇺🇸 Los Angeles, California, United States

USC Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

LAC + USC Medical Center; 🇺🇸 Los Angeles, California, United States

NEXT Oncology; 🇺🇸 San Antonio, Texas, United States

Inova Schar Cancer Institute; 🇺🇸 Fairfax, Virginia, United States

USC/Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

Henry-Joyce Cancer Clinic; 🇺🇸 Nashville, Tennessee, United States

University Of Miami Hospital and Clinics/Sylvester Comprehensive Cancer Center; 🇺🇸 Miami, Florida, United States

The University of Texas; 🇺🇸 Houston, Texas, United States

University of Washington Medical Center; 🇺🇸 Seattle, Washington, United States

Seattle Cancer Care Alliance; 🇺🇸 Seattle, Washington, United States

AdventHealth Medical Group Oncology Research at Celebration; 🇺🇸 Celebration, Florida, United States

AdventHealth Celebration Infusion Center; 🇺🇸 Celebration, Florida, United States

Oncology IDS Pharmacy; 🇺🇸 Nashville, Tennessee, United States

St. Joseph Mercy Brighton; 🇺🇸 Brighton, Michigan, United States

Keck Medical Center of USC Pasadena; 🇺🇸 Pasadena, California, United States

AdventHealth Orlando - Investigational Drug Services; 🇺🇸 Orlando, Florida, United States

AdventHealth Orlando Infusion Center; 🇺🇸 Orlando, Florida, United States

AdventHealth Hematology and Oncology; 🇺🇸 Orlando, Florida, United States

St. Joseph Mercy Hospital; 🇺🇸 Ann Arbor, Michigan, United States