Clinical trial NCT03284723: PF-06804103 Dose Escalation in HER2 Positive and Negative (Negative Only in Part 2) Solid Tumors
Official title: A Phase 1 Dose Escalation Study Evaluating the Safety and Tolerability of PF-06804103 in Patients With Human Epidermal Growth Factor Receptor 2 (HER2) Positive and Negative Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Breast Neoplasms
Keywords: HER2
PF-06804103
ADC
breast cancer
neoplasms
solid tumors
human epidermal growth receptor 2
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2017-09-15
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The study will evaluate the safety, pharmacokinetics and pharmacodynamics of increasing doses of PF-06804103 in patients with HER2 positive and negative breast and gastric cancer (HER2 positive only and gastric were studied in Part 1A only). The study will expand to look at selected doses in patients with HER2 positive and negative breast cancer.


Eligibility criteria: Inclusion Criteria:

* HER2 positive breast cancer or gastric cancer that is resistant to standard therapy or for which no standard therapy is available (Part 1A only)
* HER2 positive and negative breast cancer (Part 2A)
* HER2 negative breast cancer (Part 1B \& Part 2B)
* Performance status of 0 or 1
* Adequate bone marrow, kidney and liver function

Exclusion Criteria:

* Known CNS disease including, but not limited to, metastases
* History of exposure to certain cumulative doses of anthracyclines
* Grade 3 or higher hypersensitivity reaction to prior receipt of any antibody therapy
* Active and clinically significant bacterial, fungal, or viral infection
* Abnormal cardiac function defined by a LVEF \<50% by ECHO or MUGA
* Patients with previous history or active interstitial lung disease or pulmonary fibrosis, or a history of other clinically significant lung diseases

Primary outcomes:
measure: Number of Participants With Cycle 1 (21 Days) Dose-Limiting Toxicities (DLTs) in Part 1A
timeFrame: First cycle, Day 1 up to Day 21
measure: Number of Participants Wth Cycle 1 (28 Days) Dose-Limiting Toxicities (DLTs) in Part 1B
timeFrame: First Cycle, Day 1 up to Day 28
measure: Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs
timeFrame: From the first dose of study treatment up to a minimum of 28 calendar days after the last dose of study treatment (maximum duration between first and last dose: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B)
measure: Number of Participants With Laboratory Abnormalities-Hematology
timeFrame: From baseline to end of treatment (maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B)
measure: Number of Participants With Laboratory Abnormalities-Chemistries
timeFrame: From baseline to end of treatment (maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B)
measure: Number of Participants With Laboratory Abnormalities-Urinalysis
timeFrame: From baseline to end of treatment (maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B)
measure: Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria
timeFrame: From baseline up to follow up (at least 28 days and no more than 35 days after discontinuation of treatment), maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B
measure: Percentage of Participants With Objective Response in Part 2
timeFrame: Baseline, every 6 weeks from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 49.4 weeks)
measure: Duration of Response (DR) in Part 2
timeFrame: Baseline, every 6 weeks from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 49.4 weeks)
measure: Progression-Free Survival (PFS) in Part 2
timeFrame: Baseline, every 6 weeks from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 49.4 weeks)
measure: Time to Tumor Progression (TTP) in Part 2
timeFrame: Baseline, every 6 weeks from the start of treatment until disease progression, death, or withdrawal from treatment (maximum treatment duration: 49.4 weeks)
Secondary outcomes:
measure: Percentage of Participants With Objective Response in Part 1
timeFrame: Baseline, every 6 weeks (for Part 1A) or every 8 weeks (for Part 1B) from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 89.3 weeks for Part 1A, 53.7 weeks for Part 1B)
measure: Duration of Response (DR) in Part 1
timeFrame: Baseline, every 6 weeks (for Part 1A) or every 8 weeks (for Part 1B) from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 89.3 weeks for Part 1A, 53.7 weeks for Part 1B)
measure: Progression-Free Survival (PFS) in Part 1
timeFrame: Baseline, every 6 weeks (for Part 1A) or every 8 weeks (for Part 1B) from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 89.3 weeks for Part 1A, 53.7 weeks for Part 1B)
measure: Time to Tumor Progression (TTP) in Part 1
timeFrame: Baseline, every 6 weeks (for Part 1A) or every 8 weeks (for Part 1B) from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 89.3 weeks for Part 1A, 53.7 weeks for Part 1B)
measure: Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103
timeFrame: Prior to the start of treatment on Day 1 of Cycle 1 up to end of treatment (maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B)
measure: Number of Participants With HER2 Positivity Based on Tumor Tissue Analysis
timeFrame: Baseline
measure: Maximum Observed Concentration (Cmax) of PF-06804103 Antibody-Drug Conjugate (ADC)
timeFrame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
measure: Terminal Serum Half-Life (t1/2) of PF-06804103 ADC
timeFrame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
measure: Area Under The Serum Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06804103 ADC
timeFrame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 Day 1 for Part 1B
measure: Area Under the Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06804103 ADC
timeFrame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 4 Day 1 for Part 1B
measure: Clearance (CL) of PF-06804103 ADC
timeFrame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
measure: Volume of Distribution at Steady State (Vss) of PF-06804103 ADC
timeFrame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 4 Day 1 for Part 1B
measure: Observed Accumulation Ratio (Rac) of PF-06804103 ADC
timeFrame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 Day 1, pre-dose, 1 hour post-dose of Cycle 3 Day 1 for Part 1B
measure: Cmax of PF-06804103 Total Antibody
timeFrame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
measure: t1/2 of PF-06804103 Total Antibody
timeFrame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
measure: AUCinf of PF-06804103 Total Antibody
timeFrame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 Day 1 for Part 1B
measure: AUCtau of PF-06804103 Total Antibody
timeFrame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 4 Day 1 for Part 1B
measure: CL of PF-06804103 Total Antibody
timeFrame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
measure: Vss of PF-06804103 Total Antibody
timeFrame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 4 Day 1 for Part 1B
measure: Rac of PF-06804103 Total Antibody
timeFrame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 Day 1, pre-dose, 1 hour post-dose of Cycle 3 Day 1 for Part 1B
measure: Cmax of PF-06380101 Unconjugated Payload
timeFrame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
measure: Time for Cmax (Tmax) of PF-06380101 Unconjugated Payload
timeFrame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
measure: t1/2 of PF-06380101 Unconjugated Payload
timeFrame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
measure: AUCinf of PF-06380101 Unconjugated Payload
timeFrame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 Day 1 for Part 1B
measure: AUCtau of PF-06380101 Unconjugated Payload
timeFrame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 4 Day 1 for Part 1B
measure: Rac of PF-06380101 Unconjugated Payload
timeFrame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 Day 1, pre-dose, 1 hour post-dose of Cycle 3 Day 1 for Part 1B
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Banner-University Medical Center Tucson
state: Arizona
city: Tucson
country: United States
facility: The University of Arizona Cancer Center - North Campus
state: Arizona
city: Tucson
country: United States
facility: The University of Arizona Cancer Center
state: Arizona
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
state: California
city: Los Angeles
country: United States
facility: UCLA Health (main campus)
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology/Oncology
state: California
city: Santa Monica
country: United States
facility: Santa Monica - UCLA Medical Center and Orthopaedic Hospital
state: California
city: Santa Monica
country: United States
facility: UCLA Dept of Medicine - Hematology/Oncology, Santa Monica
state: California
city: Santa Monica
country: United States
facility: UCLA Health, Santa Monica
state: California
city: Athens
country: United States
facility: Northside Hospital Inc.- GCS/Athens
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Cancer Care - Atlanta
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital, Inc. - GCS/Northside
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Blairsville
country: United States
facility: Northside Hospital,Inc.-GCS /Blairsville
state: Georgia
city: Canton
country: United States
facility: Northside Hospital, Inc. - GCS/Canton
state: Georgia
city: Cumming
country: United States
facility: Atlanta Cancer Care - Cumming
state: Georgia
city: Decatur
country: United States
facility: Northside Hospital, Inc.-GCS/Stemmer
state: Georgia
city: Duluth
country: United States
facility: Suburban Hematology-Oncology Associates - Duluth
state: Georgia
city: Jonesboro
country: United States
facility: Atlanta Cancer Care - Lake Spivey
state: Georgia
city: Lawrenceville
country: United States
facility: Suburban Hematology-Oncology Associates- Lawrenceville
state: Georgia
city: Macon
country: United States
facility: Northside Hospital, Inc. - GCS/Macon
state: Georgia
city: Marietta
country: United States
facility: Northside Hospital, Inc. GCS/Kennestone
state: Georgia
city: Omaha
country: United States
facility: Oncology Hematology West, PC dba Nebraska Cancer Specialists
state: Nebraska
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah, Huntsman Cancer Hospital
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah, Huntsman Cancer Institute
state: Utah
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Macquarie Park
country: Australia
facility: Macquarie University
state: New South Wales
city: Milan
country: Italy
facility: Istituto Clinico Humanitas U. O. Oculistica
state: Lombardia
city: Monza
country: Italy
facility: Azienda Socio-Sanitaria Territoriale Monza
state: MB
city: Milano
country: Italy
facility: Fondazione IRCCS, Istituto Nazionale dei Tumori
state: MI
city: Milano
country: Italy
facility: Divisione di Cardiologia - Istituto Europeo di Oncologia Divisione di Medicina Nucleare
state: MI
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
state: MI
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Pyatigorsk
country: Russian Federation
facility: LLC "Clinica UZI 4D"
state: Stavropol Region
city: Saint-Petersburg
country: Russian Federation
facility: Private Healthcare Institution "Clinical hospital "RZD-Medicine" of Saint-Petersburg
city: Pozuelo de Alarcón
country: Spain
facility: Hospital Universitario Quirón Madrid
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: