Clinical trial NCT04171141: Study to Test the Safety and Tolerability of PF-07062119 in Patients With Selected Advanced or Metastatic Gastrointestinal Tumors.
Official title: A PHASE 1 DOSE ESCALATION AND EXPANSION STUDY EVALUATING THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS AND ANTI TUMOR ACTIVITY OF PF-07062119 IN PATIENTS WITH ADVANCED GASTROINTESTINAL TUMORS
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Gastrointestinal Tumors
Colorectal Adenocarcinomas
Gastric Adenocarcinomas
Esophageal Adenocarcinomas
Keywords: Gastric cancer
Esophageal cancer
Colorectal cancer
Advanced esophageal cancer
Metastatic esophageal cancer
Advanced colorectal cancer
Metastatic gastric cancer
Advanced gastric cancer
Metastatic colorectal cancer
GUCY2c
Anti-PD1
Anti-VEGF
Measurable disease
PF-07062119
PF-06801591
Bevacizumab
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2019-11-20
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: A phase 1, open-label, dose escalation and expansion study of PF-07062119 in patients with selected advanced or metastatic gastrointestinal tumors

Detailed description: This is a Phase 1, open-label, multi-center, non-randomized, multiple dose, safety, tolerability, pharmacokinetic, and pharmacodynamic study of PF-07062119 administered as a single agent in sequential dose levels and then in combination with anti-programmed cell death -1 protein (anti-PD-1) and in combination with an anti-vascular endothelial growth factor (anti-VEGF). In Part 1A, successive cohorts of patients will receive escalating doses of PF-007062119 and then in dose finding (Part 1B) with PF-07062119 in combination with anti-PD-1 and in combination with anti-VEGF. This study contains 2 parts, dose escalation with single agent (Part 1A) and then dose finding with PF-007062119 in combination with ant-PD-1 and in combination with anti-VEGF (Part 1B) followed by dose expansion arms as a single agent and PF-07062119 in combination with anti-PD 1 and in combination with anti-VEGF (Part 2).

Eligibility criteria: Inclusion Criteria:

* For Part 1 and Part 2, diagnosis of advanced/metastatic colorectal, gastric or esophageal adenocarcinoma that is resistant to standard therapy or for which no local regulatory approved standard therapy is available that would confer significant benefit.
* For Part 2, diagnosis of colorectal adenocarcinoma that is resistant to standard therapy or for which no standard therapy is available
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
* Measurable disease or non-measurable disease and refractory to or intolerant of existing therapies (Part 1)
* Measurable disease as defined by RECIST 1.1 is required (Part 2)

Exclusion Criteria:

* Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases
* Other active malignancy within 3 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ
* Major surgery or radiation within 3 weeks prior to study entry
* Last anti-cancer treatment within 4 weeks prior to study entry
* Active or history of clinically significant autoimmune disease that required systemic immunosuppressive medication
* Active or history of clinically significant gastrointestinal disease
* Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry
* Pregnant or breastfeeding female patients

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs) Assessed Through Cycle 1
timeFrame: 28 Days
measure: Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs),Treatment-Emergent Serious Adverse Events (TESAEs), Maximum Grade 3 or 4 and 5 TEAEs
timeFrame: 4 Years
measure: Number of Participants With Treatment-Related TEAEs, TESAEs, Maximum Grade 3 or 4 and 5 TEAEs
timeFrame: 4 Years
measure: Number of Participants With CTCAE Grade 3 or 4 Hematology Laboratory Abnormalities
timeFrame: 4 Years
measure: Number of Participants With CTCAE Grade 3 or 4 Chemistry Laboratory Abnormalities
timeFrame: 4 Years
Secondary outcomes:
measure: Cycle 1 and Cycle 4 PF-07062119 PK Parameters: Maximum Concentration (Cmax) - Priming Cohorts
timeFrame: Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 4 Day 1
measure: Cycle 1 and Cycle 4 PF-07062119 PK Parameters: Cmax - Non-Priming Cohorts
timeFrame: Cycle 1 Day 1 and Cycle 4 Day 1
measure: Cycle 1 and Cycle 4 PF-07062119 PK Parameters: Time to Achieve Cmax (Tmax) - Priming Cohorts
timeFrame: Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 4 Day 1
measure: Cycle 1 and Cycle 4 PF-07062119 PK Parameters: Tmax - Non-Priming Cohorts
timeFrame: Cycle 1 Day 1 and Cycle 4 Day 1
measure: Cycle 1 and Cycle 4 PF-07062119 PK Parameters: Area Under the Serum Concentration-Time Profile From Time 0 to Time Tau, the Dosing Interval (AUCtau) - Priming Cohorts
timeFrame: Cycle 1 Day 1 and Cycle 4 Day 1
measure: Cycle 1 and Cycle 4 PF-07062119 PK Parameters: AUCtau - Non-Priming Cohorts
timeFrame: Cycle 1 Day 1 and Cycle 4 Day 1
measure: Cycle 1 and Cycle 4 PF-07062119 PK Parameters: Area Under the Serum Concentration-Time Profile From Day 1 to Day 7 (168 Hours) (AUC168) - Priming Cohorts
timeFrame: Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 4 Day 1
measure: Cycle 1 and Cycle 4 PF-07062119 PK Parameters: AUC168 - Non-Priming Cohorts
timeFrame: Cycle 1 Day 1 and Cycle 4 Day 1
measure: Pre-dose Trough Concentrations After Multiple Doses of PF-07062119
timeFrame: Cycle 1 Day 15, Cycle 2 Days 1 and 15, Cycle 3 Days 1 and 15, Cycle 4 Days 1 and 15, Cycle 5 Day 1, Cycle 8 Day 1 and Cycle 11 Day 1
measure: Incidence of Anti-Drug Antibody (ADA) Positive Against PF-07062119
timeFrame: Pre-dose on Cycle 1 Day 1 and Day 15; Day 1 of Cycles 2 to 4; Day 1 of every 3rd cycle since Cycle 5
measure: Titers of ADA Against PF-07062119
timeFrame: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 and End of Treatment
measure: Incidence of Neutralizing Antibody (NAb) Positive Against PF-07062119
timeFrame: Pre-dose on Cycle 1 Day 1 and Day 15; Day 1 of Cycles 2 to 4; Day 1 of every 3rd cycle since Cycle 5
measure: Incidence of ADA Positive Against PF-06801591
timeFrame: Cycle 1 Day 1 and Day 15, Cycle 2 Day 1 and Day 15, Cycle 3 Day 1 and Day 15, Cycle 4 Day 15, Cycle 5 Day 15 and End of Treatment
measure: Percent Change From Baseline in Immune Biomarkers (CD3+ and CD8+ Cells/mm2 CT+, PD-L1 Tumor Cell Membrane Staining and PD-L1 Positive Immune Cells Per Tumor Area) in Pre-treatment and On-Treatment Paired Tumor Biopsies
timeFrame: Baseline (Baseline was defined as the time closest to, but prior to, the start of study drug administration in the first cycle), Cycle 3 Day 1
measure: Number of Participants With Confirmed Objective Response
timeFrame: Baseline up to maximum of 4 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
state: California
city: Duarte
country: United States
facility: City of Hope IDS Pharmacy
state: California
city: Los Angeles
country: United States
facility: UCLA Department of Medicine: Hematology-Oncology
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology Oncology - Santa Monica
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
state: Colorado
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center Rockefeller Outpatient Pavillion
state: New York
city: New York
country: United States
facility: Evelyn H. Lauder Breast and Imaging Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center - Main Campus
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Christus Santa Rosa Hospital
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: