Study to Test the Safety and Tolerability of PF-07062119 in Patients With Selected Advanced or Metastatic Gastrointestinal Tumors.

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

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

Study Overview

• Status: Terminated
• Conditions: Gastrointestinal Tumors; Esophageal Adenocarcinomas; Colorectal Adenocarcinomas; Gastric Adenocarcinomas
• Intervention / Treatment: Drug: PF-07062119; Drug: Anti-PD1; Drug: Anti-VEGF

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).

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
    • Parkville, Victoria, Australia, 3050
      • The Royal Melbourne Hospital
• Japan
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
    • Duarte, California, United States, 91010
      • City of Hope IDS Pharmacy
    • Los Angeles, California, United States, 90055
      • UCLA Department of Medicine: Hematology-Oncology
    • Santa Monica, California, United States, 90404
      • UCLA Hematology Oncology - Santa Monica
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • START Midwest
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center - Main Campus
    • New York, New York, United States, 10022
      • Memorial Sloan Kettering Cancer Center Rockefeller Outpatient Pavillion
    • New York, New York, United States, 10065
      • Evelyn H. Lauder Breast and Imaging Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • NEXT Oncology
    • San Antonio, Texas, United States, 78229
      • Christus Santa Rosa Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; Single Agent Dose Escalation	Drug: PF-07062119; PF-07062119
Experimental: Dose Finding Anti-PD-1 Combination; Part 1B PF-07062119 plus anti-PD-1	Drug: PF-07062119; PF-07062119; Drug: Anti-PD1; Anti-PD1 PF-06801591
Experimental: Dose Finding anti-VEGF Combination; Part 1B PF-07062119 plus anti-VEGF	Drug: PF-07062119; PF-07062119; Drug: Anti-VEGF; Anti-VEGF IV (bevacizumab)
Experimental: Dose Expansion Arm A; PF-07062119 as a Single Agent in CRC	Drug: PF-07062119; PF-07062119
Experimental: Dose Expansion Arm B; PF-07062119 in Combination with anti-PD-1 in CRC	Drug: PF-07062119; PF-07062119
Experimental: Dose Expansion Arm C; PF-07062119 in Combination with anti-VEGF in CRC	Drug: PF-07062119; PF-07062119; Drug: Anti-PD1; Anti-PD1 PF-06801591; Drug: Anti-VEGF; Anti-VEGF IV (bevacizumab)
Experimental: Dose Expansion Arm D; PF-07062119 in Combination with either anti-PD-1 or anti-VEGF in various Tumor Types	Drug: PF-07062119; PF-07062119; Drug: Anti-PD1; Anti-PD1 PF-06801591; Drug: Anti-VEGF; Anti-VEGF IV (bevacizumab)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose Limiting Toxicities (DLTs) Assessed Through Cycle 1	Hematological DLTs: Grade 3 neutropenia lasting >5 days; Febrile neutropenia defined as an ANC <1.0 x 10 ̂9/L with a single temperature of >38.3°C, or a sustained temperature of ≥38°C, for more than 1 hour; Grade ≥3 Neutropenia with infection; Grade 3 Thrombocytopenia with Grade ≥2 (clinically significant) bleeding; any Grade 4 Thrombocytopenia; Anemia or Thrombocytopenia requiring transfusion Non Hematological DLTs: Grade ≥3 fatigue lasting ≥7 days; for participants with liver, bone, or lung metastasis, an AST or ALT increase >8 x ULN or ALP >10 x ULN;; confirmed DILI meeting Hy's law criteria; Grade 3 Vomiting or Diarrhea lasting ≥3 days despite adequate treatment/other supportive care; Grade 4 Vomiting or Diarrhea; Grade ≥3 CRS regardless of duration; Grade ≥3 QTcF prolongation irrespective of duration; any death not clearly due to underlying disease or extraneous causes Clinically important/persistent toxicities were DLTs reviewed by investigators and sponsor.	28 Days
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	An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect, etc. Treatment-emergent events were with onset date occurring during the on-treatment period. AEs were documented and recorded at each visit using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.	4 Years
Number of Participants With Treatment-Related TEAEs, TESAEs, Maximum Grade 3 or 4 and 5 TEAEs	An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect, etc. Treatment-emergent events were with onset date occurring during the on-treatment period. Relatedness to study treatment was determined by the investigator. AEs were documented and recorded at each visit using the NCI CTCAE version 5.0. Severe AEs were classified as Grade 3; life-threatening consequences and urgent intervention indicated were classified as Grade 4; deaths related to AEs were classified as Grade 5.	4 Years
Number of Participants With CTCAE Grade 3 or 4 Hematology Laboratory Abnormalities	The investigator reviewed the laboratory report, documented this review, and recorded any clinically relevant changes occurring during the study in the AE section of the CRF. Clinically significant abnormal laboratory findings were those which were not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. CTCAE version 5.0 was applied.	4 Years
Number of Participants With CTCAE Grade 3 or 4 Chemistry Laboratory Abnormalities	The investigator reviewed the laboratory report, documented this review, and recorded any clinically relevant changes occurring during the study in the AE section of the case report form (CRF). Clinically significant abnormal laboratory findings were those which were not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. CTCAE version 5.0 was applied.	4 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cycle 1 and Cycle 4 PF-07062119 PK Parameters: Maximum Concentration (Cmax) - Priming Cohorts	Cmax was observed directly from data.	Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 4 Day 1
Cycle 1 and Cycle 4 PF-07062119 PK Parameters: Cmax - Non-Priming Cohorts	Cmax was observed directly from data.	Cycle 1 Day 1 and Cycle 4 Day 1
Cycle 1 and Cycle 4 PF-07062119 PK Parameters: Time to Achieve Cmax (Tmax) - Priming Cohorts	Tmax was time at which Cmax occurred which was observed directly from data as time of first occurrence.	Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 4 Day 1
Cycle 1 and Cycle 4 PF-07062119 PK Parameters: Tmax - Non-Priming Cohorts	Tmax was time at which Cmax occurred which was observed directly from data as time of first occurrence.	Cycle 1 Day 1 and Cycle 4 Day 1
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	AUCtau was area under the serum concentration-time profile from time 0 to time tau, the dosing interval, determined using linear/Log trapezoidal method.	Cycle 1 Day 1 and Cycle 4 Day 1
Cycle 1 and Cycle 4 PF-07062119 PK Parameters: AUCtau - Non-Priming Cohorts	AUCtau was area under the serum concentration-time profile from time 0 to time tau, the dosing interval, determined using linear/Log trapezoidal method.	Cycle 1 Day 1 and Cycle 4 Day 1
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	AUC168 was area under the serum concentration-time profile from Day 1 to Day 7 (168 hours) determined using linear/Log trapezoidal method.	Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 4 Day 1
Cycle 1 and Cycle 4 PF-07062119 PK Parameters: AUC168 - Non-Priming Cohorts	AUC168 was area under the serum concentration-time profile from Day 1 to Day 7 (168 hours) determined using linear/Log trapezoidal method.	Cycle 1 Day 1 and Cycle 4 Day 1
Pre-dose Trough Concentrations After Multiple Doses of PF-07062119	PF-07062119 pre-dose trough concentrations were the serum PF-07062119 concentrations assessed at 0 min of Day 1 and Day 15 in each Cycle.	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
Incidence of Anti-Drug Antibody (ADA) Positive Against PF-07062119	Blood samples of approximately 4 mL, to provide a minimum of serum 2 mL, were collected for determination of ADA against PF-07062119. All samples were collected on Day 1 of a cycle (also on Day 15, in Cycle 1 only) and drawn pre-dose - within 6 hours prior to any of the drugs being administered. Starting at Cycle 5, blood samples for ADA against PF-07062119 were collected every 3rd cycle pre-dose (ie, Cycle 5 Day 1, Cycle 8 Day 1, Cycle 11 Day 1, etc.). Participants with an unresolved AE possibly related to ADA were asked to return to the clinic for ADA and drug concentration assessments at approximately 3 month intervals until the AE or its sequelae resolved or stabilized at a level acceptable to the investigator and sponsor up to a maximum of 9 months.	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
Titers of ADA Against PF-07062119	Blood samples of approximately 4 mL, to provide a minimum of serum 2 mL, were collected for determination of ADA against PF-07062119. ADA titers of participants with positive PF-07062119 ADA (titer ≥70) are summarized.	Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 and End of Treatment
Incidence of Neutralizing Antibody (NAb) Positive Against PF-07062119	Blood samples of approximately 4 mL, to provide a minimum of serum 2 mL, were collected for determination of NAb against PF-07062119. All samples were collected on Day 1 of a cycle (also on Day 15, in Cycle 1 only) and will be drawn pre-dose - within 6 hours prior to any of the drugs being administered. Starting at Cycle 5, blood samples for NAb against PF-07062119 were collected every 3rd cycle pre-dose (ie, Cycle 5 Day 1, Cycle 8 Day 1, Cycle 11 Day 1, etc). An NAb sample was defined as positive when NAb titer was ≥2.	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
Incidence of ADA Positive Against PF-06801591	Blood samples of approximately 4 mL, to provide a minimum of serum 2 mL, were collected for determination of ADA against PF-06801591. All samples were collected on Day 1 of a cycle (also on Day 15, in Cycle 1 only) and drawn pre-dose - within 6 hours prior to any of the drugs being administered. Starting at Cycle 5, blood samples for ADA against PF-06801591 in Part 1B were collected every 3rd cycle pre-dose (ie, Cycle 5 Day 1, Cycle 8 Day 1, Cycle 11 Day 1, etc). Participants with an unresolved AE possibly related to ADA were asked to return to the clinic for ADA and drug concentration assessments at approximately 3 month intervals until the AE or its sequelae resolved or stabilized at a level acceptable to the investigator and sponsor up to a maximum of 9 months. A participant was PF-06801591 ADA positive when ADA titer was ≥99.	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
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	Tumor biospecimens from archival and/de novo biopsies were used to analyze candidate nucleic acid and protein and cellular biomarkers for their ability to inform those participants who were most likely to benefit from treatment with the study interventions. De novo tumor biopsies obtained during therapy and upon disease progression could be used to help confirm pharmacodynamic effects of treatment and investigate potential acquired mechanisms of resistance (ie, presence of but not limited to regulatory T-cells or myeloid derived suppressor cells and other immune suppressive cells or proteins).	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
Number of Participants With Confirmed Objective Response	Tumor assessments included all known or suspected disease sites. Imaging included contrast enhanced chest, abdomen and pelvis CT or MRI scans; brain CT or MRI scan for participants with known or suspected brain metastases; bone scan and/or bone x rays for participants with known or suspected bone metastases. For participants with known CT contrast allergy, a non-contrast CT of the chest with contrast enhanced abdominal and pelvic MRI could be used. The same imaging technique used to characterize each identified and reported lesion at baseline was employed in the tumor assessments. Assessment of response used Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Objective Response was defined as complete response (CR) + partial response (PR).	Baseline up to maximum of 4 years

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2019
• Primary Completion (Actual): November 28, 2023
• Study Completion (Actual): November 28, 2023

Study Registration Dates

• First Submitted: November 8, 2019
• First Submitted That Met QC Criteria: November 18, 2019
• First Posted (Actual): November 20, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 13, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Colorectal cancer; Gastric cancer; Bevacizumab; Advanced gastric cancer; Esophageal cancer; Metastatic colorectal cancer; Anti-PD1; Advanced colorectal cancer; Anti-VEGF; PF-06801591; Measurable disease; Advanced esophageal cancer; Metastatic esophageal cancer; Metastatic gastric cancer; GUCY2c; PF-07062119
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Diseases; Gastrointestinal Diseases; Neoplasms, Glandular and Epithelial; Carcinoma; Gastrointestinal Neoplasms; Adenocarcinoma; Digestive System Neoplasms
• Other Study ID Numbers: C3861001; GUCY2C (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No