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Gastrointestinal TumorsPhase 1NCT04171141

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

A Phase 1 study testing PF-07062119, Anti-PD1 and Anti-VEGF in people with Gastrointestinal Tumors and Colorectal Adenocarcinomas, run by Pfizer at 19 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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

Who is it for?
Ages 18 years and older
What is being tested?
PF-07062119, Anti-PD1 and Anti-VEGF
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
79 participants
Where
19 sitesin 3 countries
Study dates
19 Nov 2019to 28 Nov 2023
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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

Trial locations and contacts

19 sites in 3 countries.

19 sites in 3 countries

United States15 sites
  • University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)

    Aurora, Colorado, 80045

  • University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)

    Aurora, Colorado, 80045

  • University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)

    Aurora, Colorado, 80045

  • University Hospitals Cleveland Medical Center

    Cleveland, Ohio, 44106

  • City of Hope (City of Hope National Medical Center, City of Hope Medical Center)

    Duarte, California, 91010

  • City of Hope IDS Pharmacy

    Duarte, California, 91010

  • START Midwest

    Grand Rapids, Michigan, 49546

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • UCLA Department of Medicine: Hematology-Oncology

    Los Angeles, California, 90055

  • Memorial Sloan Kettering Cancer Center Rockefeller Outpatient Pavillion

    New York, New York, 10022

  • Evelyn H. Lauder Breast and Imaging Center

    New York, New York, 10065

  • Memorial Sloan Kettering Cancer Center - Main Campus

    New York, New York, 10065

  • Christus Santa Rosa Hospital

    San Antonio, Texas, 78229

  • NEXT Oncology

    San Antonio, Texas, 78229

  • UCLA Hematology Oncology - Santa Monica

    Santa Monica, California, 90404

Other trials in United States

Australia2 sites
  • Peter MacCallum Cancer Centre

    Melbourne, Victoria, 3000

  • The Royal Melbourne Hospital

    Parkville, Victoria, 3050

Other trials in Australia

Japan2 sites
  • National Cancer Center Hospital

    Chuo-ku, Tokyo, 104-0045

  • National Cancer Center Hospital East

    Kashiwa, Chiba, 277-8577

Other trials in Japan

About this study

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

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

Read the 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).

Being tested
PF-07062119, Anti-PD1, Anti-VEGF
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
Medical subject headings
Digestive System Neoplasms, Stomach Neoplasms, Esophageal Neoplasms, Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PF-07062119Drug

    PF-07062119

  • Anti-PD1Drug

    Anti-PD1 PF-06801591

  • Anti-VEGFDrug

    Anti-VEGF IV (bevacizumab)

Study groups in NCT04171141
Study groupRoleWhat they receive
Dose EscalationExperimentalSingle Agent Dose Escalation
Receives: Drug: PF-07062119
Dose Finding Anti-PD-1 CombinationExperimentalPart 1B PF-07062119 plus anti-PD-1
Receives: Drug: PF-07062119; Drug: Anti-PD1
Dose Finding anti-VEGF CombinationExperimentalPart 1B PF-07062119 plus anti-VEGF
Receives: Drug: PF-07062119; Drug: Anti-VEGF
Dose Expansion Arm AExperimentalPF-07062119 as a Single Agent in CRC
Receives: Drug: PF-07062119
Dose Expansion Arm BExperimentalPF-07062119 in Combination with anti-PD-1 in CRC
Receives: Drug: PF-07062119
Dose Expansion Arm CExperimentalPF-07062119 in Combination with anti-VEGF in CRC
Receives: Drug: PF-07062119; Drug: Anti-PD1; Drug: Anti-VEGF
Dose Expansion Arm DExperimentalPF-07062119 in Combination with either anti-PD-1 or anti-VEGF in various Tumor Types
Receives: Drug: PF-07062119; Drug: Anti-PD1; Drug: Anti-VEGF

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 28 Days

  2. 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.

    Measured: 4 Years

  3. 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.

    Measured: 4 Years

  4. 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.

    Measured: 4 Years

  5. 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.

    Measured: 4 Years

Secondary outcomes (15)
  1. Cycle 1 and Cycle 4 PF-07062119 PK Parameters: Maximum Concentration (Cmax) - Priming Cohorts

    Cmax was observed directly from data.

    Measured: Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 4 Day 1

  2. Cycle 1 and Cycle 4 PF-07062119 PK Parameters: Cmax - Non-Priming Cohorts

    Cmax was observed directly from data.

    Measured: Cycle 1 Day 1 and Cycle 4 Day 1

  3. 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.

    Measured: Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 4 Day 1

  4. 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.

    Measured: Cycle 1 Day 1 and Cycle 4 Day 1

  5. 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.

    Measured: Cycle 1 Day 1 and Cycle 4 Day 1

  6. 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.

    Measured: Cycle 1 Day 1 and Cycle 4 Day 1

  7. 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.

    Measured: Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 4 Day 1

  8. 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.

    Measured: Cycle 1 Day 1 and Cycle 4 Day 1

  9. 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.

    Measured: 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

  10. 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.

    Measured: 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

  11. 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.

    Measured: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 and End of Treatment

  12. 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.

    Measured: 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

  13. 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.

    Measured: 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

  14. 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).

    Measured: 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

  15. 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).

    Measured: Baseline up to maximum of 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Nov 2019
  2. Study start19 Nov 2019
  3. Primary completion28 Nov 2023
  4. Study completion28 Nov 2023

Why it stopped: Study was terminated due to strategic considerations and not due to safety.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
79 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04171141
Sponsor's protocol ID
C3861001
Other IDs
GUCY2C
Status last verified
Jan 2025
First submitted
8 Nov 2019
Last updated
16 Jan 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PF-07062119, Anti-PD1 and Anti-VEGF in people with Gastrointestinal Tumors and Colorectal Adenocarcinomas, run by Pfizer at 19 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 16 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States, Australia, Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose Limiting Toxicities (DLTs) Assessed Through Cycle 1 (time frame: 28 Days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2025.

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