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

NCT03854227 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: C3851001
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 22

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.

Conditions

Advanced Solid Tumors; Metastatic Solid Tumors

Outcome Measures

Primary Outcomes (6)

• Part 1A: Number of Participants With Dose-Limiting Toxicities (DLT)

  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.

  Baseline through day 29.

• Part 1A: Number of Participants With Treatment-Emergent Adverse Events (TEAE)

  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.

  Baseline up to a minimum of 28 days after last dose of study treatment (maximum of 13 months)

• Part 1A: Number of Participants With Laboratory Abnormalities

  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.

  Baseline up to a minimum of 28 days after last dose of study treatment (maximum of 12 months)

• Part 2: Number of Participants With TEAEs

  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.

  Baseline up to a minimum of 28 days after last dose of study treatment (maximum of 15 months)

• Part 2: Number of Participants With Laboratory Abnormalities

  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.

  Baseline up to a minimum of 28 days after last dose of study treatment (maximum of 8 months)

• Part 2: Number of Participants With Best Overall Response (BOR) Based on Investigator Assessment (RECIST, Version 1.1)

  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.

  From baseline up to 28 ~ 35 days after end of treatment (maximum of 6 months).

Secondary Outcomes (23)

• 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.

• 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.

• 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.

• 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.

• 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.

Study Arms (6)

Dose Escalation

EXPERIMENTAL

Participants will receive PF-06939999 orally at escalating doses in 28 day cycles on a continuous basis

Drug: 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

Drug: PF-06939999 monotherapy

Urothelial carcinoma

EXPERIMENTAL

Participants will receive PF-06939999 at the recommended Phase 2 dose in 28 day cycles on a continuous basis

Drug: PF-06939999 monotherapy

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

Drug: PF-06939999 monotherapy

Non small cell lung cancer PF-06939999 plus docetaxel

EXPERIMENTAL

Participants will receive PF-06939999 on a continuous basis in combination with docetaxel

Drug: 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

Drug: PF-06939999 in combination with docetaxel

Interventions

PF-06939999 dose escalation DRUG

PF-06939999 orally at escalating doses on a continuous basis

Also known as: PRMT5 inhibitor

Dose Escalation

PF-06939999 monotherapy DRUG

PF-06939999 at the recommended Phase 2 dose orally on a continuous basis

Also known as: PRMT5 inhibitor

Head and neck squamous cell carcinoma; Non small cell lung cancer monotherapy; Urothelial carcinoma

PF-06939999 in combination with docetaxel DRUG

PF-06939999 orally on a continuous basis in combination with docetaxel

Also known as: PRMT5 inhibitor

Non small cell lung cancer PF-06939999 plus docetaxel; Non small cell lung cancer dose finding

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (22)

Scottsdale Healthcare Hospitals d/b/a HonorHealth

Scottsdale, Arizona, 85258, United States

Location

Virginia G. Piper Cancer Pharmacy

Scottsdale, Arizona, 85258, United States

Location

Keck Hospital of USC

Los Angeles, California, 90033, United States

Location

LAC + USC Medical Center

Los Angeles, California, 90033, United States

Location

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Keck Medical Center of USC Pasadena

Pasadena, California, 91105, United States

Location

AdventHealth Celebration Infusion Center

Celebration, Florida, 34747, United States

Location

AdventHealth Medical Group Oncology Research at Celebration

Celebration, Florida, 34747, United States

Location

University Of Miami Hospital and Clinics/Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

AdventHealth Orlando - Investigational Drug Services

Orlando, Florida, 32804, United States

Location

AdventHealth Orlando Infusion Center

Orlando, Florida, 32804, United States

Location

AdventHealth Orlando

Orlando, Florida, 32804, United States

Location

St. Joseph Mercy Hospital

Ann Arbor, Michigan, 48106, United States

Location

St. Joseph Mercy Brighton

Brighton, Michigan, 48114, United States

Location

Henry-Joyce Cancer Clinic

Nashville, Tennessee, 37232, United States

Location

Oncology IDS Pharmacy

Nashville, Tennessee, 37232, United States

Location

The University of Texas

Houston, Texas, 77030, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

Inova Schar Cancer Institute

Fairfax, Virginia, 22031, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Related Publications (1)

• Guo C, Liao KH, Li M, Wang IM, Shaik N, Yin D. PK/PD model-informed dose selection for oncology phase I expansion: Case study based on PF-06939999, a PRMT5 inhibitor. CPT Pharmacometrics Syst Pharmacol. 2023 Nov;12(11):1619-1625. doi: 10.1002/psp4.12882. Epub 2022 Nov 16.

  PMID: 36394153 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

Docetaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Limitations and Caveats

The study was terminated based on a strategic decision. This decision was not due to any safety concerns or requests from any regulatory authorities.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_lnquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose Escalation and Dose expansion

Study Record Dates

• First Submitted: February 15, 2019
• First Posted: February 26, 2019
• Study Start: March 14, 2019
• Primary Completion: April 27, 2022
• Study Completion: April 27, 2022
• Last Updated: January 13, 2025
• Results First Posted: January 13, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (22)