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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04171141




Registration number
NCT04171141
Ethics application status
Date submitted
8/11/2019
Date registered
20/11/2019
Date last updated
16/01/2025

Titles & IDs
Public title
Study to Test the Safety and Tolerability of PF-07062119 in Patients With Selected Advanced or Metastatic Gastrointestinal Tumors.
Scientific 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
Secondary ID [1] 0 0
GUCY2C
Secondary ID [2] 0 0
C3861001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gastrointestinal Tumors 0 0
Colorectal Adenocarcinomas 0 0
Gastric Adenocarcinomas 0 0
Esophageal Adenocarcinomas 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 0 0 0 0
Oesophageal (gullet)
Cancer 0 0 0 0
Other cancer types
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PF-07062119
Treatment: Drugs - Anti-PD1
Treatment: Drugs - Anti-VEGF

Experimental: Dose Escalation - Single Agent Dose Escalation

Experimental: Dose Finding Anti-PD-1 Combination - Part 1B PF-07062119 plus anti-PD-1

Experimental: Dose Finding anti-VEGF Combination - Part 1B PF-07062119 plus anti-VEGF

Experimental: Dose Expansion Arm A - PF-07062119 as a Single Agent in CRC

Experimental: Dose Expansion Arm B - PF-07062119 in Combination with anti-PD-1 in CRC

Experimental: Dose Expansion Arm C - PF-07062119 in Combination with anti-VEGF in CRC

Experimental: Dose Expansion Arm D - PF-07062119 in Combination with either anti-PD-1 or anti-VEGF in various Tumor Types


Treatment: Drugs: PF-07062119
PF-07062119

Treatment: Drugs: Anti-PD1
Anti-PD1 PF-06801591

Treatment: Drugs: Anti-VEGF
Anti-VEGF IV (bevacizumab)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Dose Limiting Toxicities (DLTs) Assessed Through Cycle 1
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
28 Days
Primary outcome [2] 0 0
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
Assessment method [2] 0 0
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.
Timepoint [2] 0 0
4 Years
Primary outcome [3] 0 0
Number of Participants With Treatment-Related TEAEs, TESAEs, Maximum Grade 3 or 4 and 5 TEAEs
Assessment method [3] 0 0
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.
Timepoint [3] 0 0
4 Years
Primary outcome [4] 0 0
Number of Participants With CTCAE Grade 3 or 4 Hematology Laboratory Abnormalities
Assessment method [4] 0 0
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.
Timepoint [4] 0 0
4 Years
Primary outcome [5] 0 0
Number of Participants With CTCAE Grade 3 or 4 Chemistry Laboratory Abnormalities
Assessment method [5] 0 0
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.
Timepoint [5] 0 0
4 Years
Secondary outcome [1] 0 0
Cycle 1 and Cycle 4 PF-07062119 PK Parameters: Maximum Concentration (Cmax) - Priming Cohorts
Assessment method [1] 0 0
Cmax was observed directly from data.
Timepoint [1] 0 0
Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 4 Day 1
Secondary outcome [2] 0 0
Cycle 1 and Cycle 4 PF-07062119 PK Parameters: Cmax - Non-Priming Cohorts
Assessment method [2] 0 0
Cmax was observed directly from data.
Timepoint [2] 0 0
Cycle 1 Day 1 and Cycle 4 Day 1
Secondary outcome [3] 0 0
Cycle 1 and Cycle 4 PF-07062119 PK Parameters: Time to Achieve Cmax (Tmax) - Priming Cohorts
Assessment method [3] 0 0
Tmax was time at which Cmax occurred which was observed directly from data as time of first occurrence.
Timepoint [3] 0 0
Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 4 Day 1
Secondary outcome [4] 0 0
Cycle 1 and Cycle 4 PF-07062119 PK Parameters: Tmax - Non-Priming Cohorts
Assessment method [4] 0 0
Tmax was time at which Cmax occurred which was observed directly from data as time of first occurrence.
Timepoint [4] 0 0
Cycle 1 Day 1 and Cycle 4 Day 1
Secondary outcome [5] 0 0
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
Assessment method [5] 0 0
AUCtau was area under the serum concentration-time profile from time 0 to time tau, the dosing interval, determined using linear/Log trapezoidal method.
Timepoint [5] 0 0
Cycle 1 Day 1 and Cycle 4 Day 1
Secondary outcome [6] 0 0
Cycle 1 and Cycle 4 PF-07062119 PK Parameters: AUCtau - Non-Priming Cohorts
Assessment method [6] 0 0
AUCtau was area under the serum concentration-time profile from time 0 to time tau, the dosing interval, determined using linear/Log trapezoidal method.
Timepoint [6] 0 0
Cycle 1 Day 1 and Cycle 4 Day 1
Secondary outcome [7] 0 0
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
Assessment method [7] 0 0
AUC168 was area under the serum concentration-time profile from Day 1 to Day 7 (168 hours) determined using linear/Log trapezoidal method.
Timepoint [7] 0 0
Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 4 Day 1
Secondary outcome [8] 0 0
Cycle 1 and Cycle 4 PF-07062119 PK Parameters: AUC168 - Non-Priming Cohorts
Assessment method [8] 0 0
AUC168 was area under the serum concentration-time profile from Day 1 to Day 7 (168 hours) determined using linear/Log trapezoidal method.
Timepoint [8] 0 0
Cycle 1 Day 1 and Cycle 4 Day 1
Secondary outcome [9] 0 0
Pre-dose Trough Concentrations After Multiple Doses of PF-07062119
Assessment method [9] 0 0
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.
Timepoint [9] 0 0
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
Secondary outcome [10] 0 0
Incidence of Anti-Drug Antibody (ADA) Positive Against PF-07062119
Assessment method [10] 0 0
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.
Timepoint [10] 0 0
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
Secondary outcome [11] 0 0
Titers of ADA Against PF-07062119
Assessment method [11] 0 0
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.
Timepoint [11] 0 0
Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 and End of Treatment
Secondary outcome [12] 0 0
Incidence of Neutralizing Antibody (NAb) Positive Against PF-07062119
Assessment method [12] 0 0
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.
Timepoint [12] 0 0
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
Secondary outcome [13] 0 0
Incidence of ADA Positive Against PF-06801591
Assessment method [13] 0 0
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.
Timepoint [13] 0 0
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
Secondary outcome [14] 0 0
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
Assessment method [14] 0 0
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).
Timepoint [14] 0 0
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
Secondary outcome [15] 0 0
Number of Participants With Confirmed Objective Response
Assessment method [15] 0 0
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).
Timepoint [15] 0 0
Baseline up to maximum of 4 years

Eligibility
Key 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)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/11/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/11/2023
Sample size
Target
Accrual to date
Final
79
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [2] 0 0
The Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
Japan
State/province [7] 0 0
Chiba
Country [8] 0 0
Japan
State/province [8] 0 0
Tokyo

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT04171141