Description:
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.
Title
- Brief Title: A Dose Escalation Study Of PF-06939999 In Participants With Advanced Or Metastatic Solid Tumors
- Official Title: A PHASE 1 STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF ESCALATING DOSES OF PF-06939999 (PRMT5 INHIBITOR) IN PARTICIPANTS WITH ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER, HEAD AND NECK SQUAMOUS CELL CARCINOMA, ESOPHAGEAL CANCER, ENDOMETRIAL CANCER, CERVICAL CANCER AND BLADDER CANCER
Clinical Trial IDs
- ORG STUDY ID:
C3851001
- NCT ID:
NCT03854227
Conditions
- Advanced Solid Tumors
- Metastatic Solid Tumors
Interventions
| Drug | Synonyms | Arms |
|---|
| PF-06939999 dose escalation | PRMT5 inhibitor | Dose Escalation |
| PF-06939999 monotherapy | PRMT5 inhibitor | Head and neck squamous cell carcinoma |
| PF-06939999 in combination with docetaxel | PRMT5 inhibitor | Non small cell lung cancer PF-06939999 plus docetaxel |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Dose Escalation | Experimental | Participants will receive PF-06939999 orally at escalating doses in 28 day cycles on a continuous basis | - PF-06939999 dose escalation
|
| Non small cell lung cancer monotherapy | Experimental | Participants will receive PF-06939999 at the recommended Phase 2 dose in 28 day cycles on a continuous basis | |
| Urothelial carcinoma | Experimental | 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 | Experimental | 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 | Experimental | Participants will receive PF-06939999 on a continuous basis in combination with docetaxel | - PF-06939999 in combination with docetaxel
|
| Non small cell lung cancer dose finding | Experimental | Participants will receive PF-06939999 on a continuous basis at escalating doses in combination with docetaxel | - PF-06939999 in combination with docetaxel
|
Eligibility Criteria
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
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
| 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) |
| Time Frame: | Baseline through day 28 |
| Safety Issue: | |
| Description: | DLTs will be evaluated during the first cycle. The number of DLTs will be used to determine the maximum tolerated dose (MTD) |
Secondary Outcome Measures
| Measure: | Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax) |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | Single dose PK will be calculated including Maximum Observed Plasma Concentration (Cmax). |
| Measure: | Pharmacokinetic Parameters: Time to reach Maximum Observed Plasma Concentration (Tmax) |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | Single dose PK will be calculated including Time to reach Maximum Observed Plasma Concentration (Tmax). |
| Measure: | Pharmacokinetic Parameters: Area Under the Curve from time 0 to the last sampling time point within the dose interval (AUClast) |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | 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) |
| Measure: | Pharmacokinetic Parameters: Terminal elimination half life (t1/2) |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | Single dose PK will be calculated including, as data permit, terminal elimination half life (t1/2) |
| Measure: | Pharmacokinetic Parameters: AUC from time 0 extrapolated to infinity (AUCinf) |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | Single dose PK will be calculated including, as data permit, Area Under the Curve from time 0 extrapolated to infinity (AUCinf) |
| Measure: | Pharmacokinetic Parameters: Apparent oral plasma clearance (CL/F) |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | Single dose PK will be calculated including, as data permit, apparent oral plasma clearance (CL/F) |
| Measure: | Pharmacokinetic Parameters: Apparent volume of distribution (Vz/F) |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | Single dose PK will be calculated including, as data permit, apparent volume of distribution (Vz/F) |
| Measure: | Pharmacokinetic Parameters: Maximum Observed Steady State Plasma Concentration (Css,max) |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | Multiple dose PK will be calculated including Maximum Observed Steady State Plasma Concentration (Css,max). |
| Measure: | Pharmacokinetic Parameters: Time to reach Maximum Observed Steady State Plasma Concentration (Tss,max) |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | Multiple dose PK will be calculated including Time to reach Maximum Observed Steady State Plasma Concentration (Tss,max). |
| Measure: | Pharmacokinetic Parameters: Area Under the Curve within one dose interval (AUCss,t) |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | Multiple dose PK will be calculated including Area Under the Curve within one dose interval (AUCss,t) |
| Measure: | Pharmacokinetic Parameters: Steady state apparent oral plasma clearance (CL/F) |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | Multiple dose PK will be calculated including, as data permit, steady state apparent oral plasma clearance (CL/F) |
| Measure: | Pharmacokinetic Parameters: Steady state apparent volume of distribution (Vss/F) |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | Multiple dose PK will be calculated including, as data permit, steady state apparent volume of distribution (Vss/F) |
| Measure: | Pharmacokinetic Parameters: Accumulation ratio (Rac) |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | Multiple dose PK will be calculated including, as data permit, accumulation ratio (Rac) |
| Measure: | Duration of response (DOR) |
| Time Frame: | Baseline through up to 2 years or until disease progression |
| Safety Issue: | |
| Description: | DOR as assessed using RECIST 1.1 |
| Measure: | Progression free survival (PFS) |
| Time Frame: | Baseline through up to 2 years or until disease progression |
| Safety Issue: | |
| Description: | PFS as assessed using RECIST 1.1. |
| Measure: | Time to progression (TTP) |
| Time Frame: | Baseline through up to 2 years or until disease progression |
| Safety Issue: | |
| Description: | TTP as assessed using RECIST 1.1. |
| Measure: | Overall Survival (OS) |
| Time Frame: | Baseline through up to 2 years |
| Safety Issue: | |
| Description: | Proportion of participants alive at 6 months, 1 year and 2 years. |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Pfizer |
Last Updated
August 19, 2021
