Clinical trial NCT02078752: A Study Of PF-06647263 In Patients With Advanced Solid Tumors
Official title: A FIRST-IN-HUMAN PHASE 1, DOSE ESCALATION, SAFETY AND PHARMACOKINETIC STUDY OF PF-06647263 IN ADULT PATIENTS WITH ADVANCED SOLID TUMORS
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Neoplasms
Triple-Negative Breast Cancer
Keywords: ADC
PF-06647263
solid tumors
tumors
neoplasm metastasis
TNBC
Triple negative breast cancer
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2014-03-05
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To assess the safety and tolerability at increasing dose levels of PF-06647263 in patients with advanced solid tumors in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.

Detailed description: The clinical study will include 2 parts. Part 1 will estimate the MTD in dose escalation cohorts in patients with advanced solid tumors for whom no standard therapy is available in order to establish the RP2D. Part 2 will include patients with previously treated metastatic triple negative breast cancer (TNBC).

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 advanced triple negative 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
* Active and clinically significant bacterial, fungal or viral infection

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs) (Part 1)
timeFrame: Baseline up to Cycle 2 Day 1 (22 days)
measure: Percentage of Participants With Objective Response (Part 2)
timeFrame: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) (All Causality, All Cycles)
timeFrame: Baseline up to 28 days after the last treatment administration (Approximately 13 months)
measure: Number of Participants With Treatment-Emergent AEs (Treatment-related, All Cycles)
timeFrame: Baseline up to 28 days after the last treatment administration (Approximately 13 months)
measure: Number of Participants With Treatment-Emergent Serious Adverse Events (SAEs) (All Causality, All Cycles)
timeFrame: Baseline up to 28 days after the last treatment administration (Approximately 13 months)
measure: Number of Participants With Treatment-Emergent SAEs (Treatment-related, All Cycles)
timeFrame: Baseline up to 28 days after the last treatment administration (Approximately 13 months)
measure: Number of Participants With Vital Signs Abnormalities
timeFrame: Baseline, Days 1, 8, 15 of each cycle, and post treatment period. (Approximately 13 months)
measure: Area Under the Serum Concentration-time Profile From Time 0 to the 504-hour Time Point (AUC504) of PF-06647263
timeFrame: Cycle 1 Day 1: predose, 1, 4, 24, 72 hrs postdose, Cycle 1 Days 8 and 15: predose, 1 and 72 hrs postdose, up to Cycle 2 Day 1 predose (504 hr).
measure: Area Under the Concentration-Time Profile From Time 0 to Time Tau (AUCtau) of PF-06647263
timeFrame: QW: C1D1: predose, 1,4,24,72 hrs postdose, C1D8 & 15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
measure: Maximum Observed Serum Concentration (Cmax) of PF-06647263
timeFrame: QW: C1D1: predose, 1,4,24,72 hrs postdose, C1D8 & 15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
measure: Time for Cmax (Tmax) of PF-06647963
timeFrame: QW: C1D1: predose, 1,4,24,72 hrs postdose, C1D8 & 15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
measure: Clearance (CL) of PF-06647263
timeFrame: QW: C1D15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
measure: Volume of Distribution at Steady State (Vss) of PF-06647263
timeFrame: QW: C1D15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
measure: Terminal Serum Half-life (t1/2) of PF-06647263
timeFrame: Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
measure: AUC504 of Total Antibody
timeFrame: Cycle 1 Day 1: predose, 1, 4, 24, 72 hrs postdose, Cycle 1 Days 8 and 15: predose, 1 and 72 hrs postdose, up to Cycle 2 Day 1 predose (504 hr).
measure: AUCtau of Total Antibody
timeFrame: QW: C1D1: predose, 1,4,24,72 hrs postdose, C1D8 & 15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
measure: Cmax of Total Antibody
timeFrame: QW: C1D1: predose, 1,4,24,72 hrs postdose, C1D8 & 15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
measure: Tmax of Total Antibody
timeFrame: QW: C1D1: predose, 1,4,24,72 hrs postdose, C1D8 & 15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
measure: CL of Total Antibody
timeFrame: QW: C1D15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
measure: Vss of Total Antibody
timeFrame: QW: C1D15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
measure: t1/2 of Total Antibody
timeFrame: Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
measure: Cmax of Unconjugated Payload CL-184538
timeFrame: Every Cycle: Days 1, 8, 15. up to end of treatment (Approximately 13 months)
measure: Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
timeFrame: Baseline up to 7 days post end of treatment (Approximately 13 months)
measure: Number of Participants With Positive Antibodies for PF-06647263, Total Antibody (PF-06523432), and Unconjugated Payload (CL-184538)
timeFrame: QW: C1:D1&D15; every other cycle: D1; end of treatment. Q3W:C1: D1&D15; Cycles 2 through 4: D1; every other cycle: D1; end of treatment.
measure: Number of Participants With Positive Neutralizing Anti PF-06647263 Antibody
timeFrame: QW: C1:D1&D15; every other cycle: D1; end of treatment. Q3W:C1: D1&D15; Cycles 2 through 4: D1; every other cycle: D1; end of treatment.
measure: Number of Participants With Treatment-Emergent and Treatment-Boosted Anti PF-06647263 Antibody
timeFrame: QW: C1:D1&D15; every other cycle: D1; end of treatment. Q3W:C1: D1&D15; Cycles 2 through 4: D1; every other cycle: D1; end of treatment.
measure: Percentage of Participants With Objective Response (Part 1)
timeFrame: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months
measure: Percentage of Participants With Clinical Benefit Response
timeFrame: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months
measure: Progression Free Survival
timeFrame: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months
measure: Overall Survival (OS)-Stratifying for EFNA4 Expression (Part 2)
timeFrame: Baseline up to 24 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham & Women's Hospital (BWH)
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute (DFCI)
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers Of Nevada
state: Nevada
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Hospital / University of Utah
state: Utah
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute-University of Utah
state: Utah
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Garrido-Laguna I, Krop I, Burris HA 3rd, Hamilton E, Braiteh F, Weise AM, Abu-Khalaf M, Werner TL, Pirie-Shepherd S, Zopf CJ, Lakshminarayanan M, Holland JS, Baffa R, Hong DS. First-in-human, phase I study of PF-06647263, an anti-EFNA4 calicheamicin antibody-drug conjugate, in patients with advanced solid tumors. Int J Cancer. 2019 Oct 1;145(7):1798-1808. doi: 10.1002/ijc.32154. Epub 2019 Feb 23.