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A Study of PF-07260437 in Advanced or Metastatic Solid Tumors (C4431001)

Primary Purpose

Ovarian Neoplasms, Endometrial Neoplasms, Breast Neoplasms

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
PF-07260437
B7-H4 IHC
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Neoplasms focused on measuring Cancer of Endometrium, Cancer of the Endometrium, Carcinoma of Endometrium, Endometrial Cancer, Endometrial Carcinoma, Endometrium Cancer, Neoplasms, Endometrial, Cancer of Ovary, Cancer of the Ovary, Neoplasms, Ovarian, Ovarian Cancer, Ovary Cancer, Ovary Neoplasms, Breast Cancer, Breast Carcinoma, Breast Tumors, Cancer of Breast, Cancer of the Breast, Human Mammary Carcinoma, Malignant Neoplasm of Breast, Malignant Tumor of Breast

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Part 1: Histological/cytological diagnosis of selected locally advanced or metastatic breast cancer, endometrial cancer and ovarian cancer
  • Part 2A:In second line or more, participants with histological/cytological diagnosis of locally advanced or metastatic HR+ HER2- breast cancer showing high B7-H4 expression
  • Part 2B: In second line or more participants with histological or cytological diagnosis of locally advance or metastatic HR+ Her2- breast cancer or triple negative breast cancer (TNBC) with no biomarker pre-selection
  • Part 2C: In second line or more participants with histological diagnosis of locally advance or metastatic triple negative breast cancer with high B7-H4 expression
  • Thyroid function within normal laboratory range; in participants with abnormal thyroid function if Free T4 is normal and participant is clinically euthyroid, participants is eligible

Exclusion Criteria:

  • Participants with any active malignancy within 3 years prior to enrollment
  • Participants with advanced/metastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term (including participants with massive uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and over 50% liver involvement).
  • History of Grade ≥3 immune mediated adverse events (including liver function tests that where considered drug related and cytokine release syndrome) that was considered related to prior immune modulatory therapy (eg, immune checkpoint inhibitors, co stimulatory agents, etc.) and required immunosuppressive therapy within 1 year of treatment.

Sites / Locations

  • City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
  • Moffitt Cancer Center at McKinley Campus
  • Moffitt Cancer Center
  • University of Chicago Medical Center
  • University of Chicago Comprehensive Cancer Center at Silver Cross Hospital
  • The University of Chicago Medicine Center of Advanced Care Orland Park
  • Montefiore Einstein Center for Cancer Care
  • NEXT Oncology
  • Swedish Cancer Institute Edmonds Campus
  • Swedish Cancer Institute
  • Fred Hutchinson Cancer Center
  • University of Washington Medical Center - Mountlake
  • Pan American Center for Oncology Trials- Hospital Oncologico
  • Pan American Center for Oncology Trials

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Monotherapy dose escalation (Part 1)

Dose Expansion (Part 2A) - Tumor specific Arm A

Dose Expansion (Part 2B) - Tumor specific Arm B

Dose Expansion (Part 2C) - Tumor specific Arm C

Arm Description

Participants will receive PF-07260437

Participants will receive PF-07260437

Participants will receive PF-07260437

Participants will receive PF07260437

Outcomes

Primary Outcome Measures

Number of participants with dose limiting toxicities (DLTs) in Dose escalation
DLTs will be evaluated in Part 1. The number of DLTs will be used to determine the dose escalation decision and recommended dose of PF-07260437
Number of participants with adverse events
Number of participants with clinically significant laboratory abnormalities
Number of participants with clinical adverse events at the recommended dose for expansion
Number of participants with clinically significant laboratory abnormalities at recommended dose for expansion

Secondary Outcome Measures

Number of participants with immune related adverse events
Single dose: Maximal concentration (Cmax)
PK assessment for PF-07260437
Time to maximal plasma concentration (Tmax)
PK assessment of PF-07260437
Single dose: Area Under the Curve (AUClast)
PK assessment of PF-07260437
Plasma Decay Half-live (t1/2)
PK assessment of PF-07260437
Area Under the Curve from Time Zero to Extrapolated Infinite Time (AUCinf)
PK assessment of PF-07260437
Apparent Volume of Distribution (Vz/F)
PK assessment of PF-0260347
Accumulation Ratio (Rac)
PK assessment for PF-07260437
Apparent Oral Clearance (CL/F)
PF assessment of PF-07260437
Apparent Oral Clearance of Study Drug (CLss/F)
PK assessment for PF-07260437
Area under the curve at steady state under a dosing interval (AUCss,τ)
PK assessment of PF-07260437
Maximum Observed Plasma Concentration at Steady State (Cmax,ss)
PK assessment of PF-07260437
Time to reach maximum Observed Plasma Concentration at Steady State (Tmax,ss)
PK assessment of PF-07260437
Minimum Observed Plasma Trough Concentration at Steady State (Cmin,ss)
PK assessment for PF-07260437
Incident and titers of anti-body drug antibody against PF-07260437
Immunogenicity of PF-07260437
Incident and titers of anti-body neutralizing antibody against PF-07260437
Immunogenicity of PF-07260437
Number of participants with immune related adverse events at the recommended dose for expansion
Duration of response (DOR) in dose expansion
DOR as assessed using RECIST 1.1 and irRECIST
Time to progression (TTP) in dose expansion
TTP as assessed using RECIST 1.1 and irRECIST
Objective response rate (ORR) in dose expansion
ORR as assessed using RECIST 1.1 and irRECIST
Progression free survival (PFS)
PFS as assessed using RECIST 1.1 and irRECIST
Overall survival (OS) in the Expansion Cohorts (Part 2)
Proportion of participants alive
Phenotypes and quantity of tumor infiltrating lymphocytes (TIL) before and after PF-07260437 treatment
Immune Cells assessments from paired biopsies

Full Information

First Posted
September 24, 2021
Last Updated
September 15, 2023
Sponsor
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT05067972
Brief Title
A Study of PF-07260437 in Advanced or Metastatic Solid Tumors
Acronym
C4431001
Official Title
A PHASE 1 DOSE ESCALATION AND EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETIC, PHARMACODYNAMIC, AND ANTITUMOR ACTIVITY OF PF-07260437 IN ADVANCED OR METASTATIC SOLID TUMORS
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 7, 2021 (Actual)
Primary Completion Date
January 15, 2024 (Anticipated)
Study Completion Date
January 15, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
A study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of PF-07260437, a B7-H4 x CD3 bispecific mAb, in participants aged ≥18 years of age with advanced or metastatic breast cancer, ovarian cancer or endometrial cancer. Adult participants with other advanced or metastatic high B7-H4 expressing tumors may be considered after discussion with and approval from sponsor.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Neoplasms, Endometrial Neoplasms, Breast Neoplasms
Keywords
Cancer of Endometrium, Cancer of the Endometrium, Carcinoma of Endometrium, Endometrial Cancer, Endometrial Carcinoma, Endometrium Cancer, Neoplasms, Endometrial, Cancer of Ovary, Cancer of the Ovary, Neoplasms, Ovarian, Ovarian Cancer, Ovary Cancer, Ovary Neoplasms, Breast Cancer, Breast Carcinoma, Breast Tumors, Cancer of Breast, Cancer of the Breast, Human Mammary Carcinoma, Malignant Neoplasm of Breast, Malignant Tumor of Breast

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Monotherapy dose escalation (Part 1)
Arm Type
Experimental
Arm Description
Participants will receive PF-07260437
Arm Title
Dose Expansion (Part 2A) - Tumor specific Arm A
Arm Type
Experimental
Arm Description
Participants will receive PF-07260437
Arm Title
Dose Expansion (Part 2B) - Tumor specific Arm B
Arm Type
Experimental
Arm Description
Participants will receive PF-07260437
Arm Title
Dose Expansion (Part 2C) - Tumor specific Arm C
Arm Type
Experimental
Arm Description
Participants will receive PF07260437
Intervention Type
Drug
Intervention Name(s)
PF-07260437
Other Intervention Name(s)
B7-H4
Intervention Description
B7-H4 x CD3 bi-specific mAb
Intervention Type
Diagnostic Test
Intervention Name(s)
B7-H4 IHC
Intervention Description
B7-H4 expression
Primary Outcome Measure Information:
Title
Number of participants with dose limiting toxicities (DLTs) in Dose escalation
Description
DLTs will be evaluated in Part 1. The number of DLTs will be used to determine the dose escalation decision and recommended dose of PF-07260437
Time Frame
Baseline through 28 days after first dose
Title
Number of participants with adverse events
Time Frame
Baseline through up to 2 years
Title
Number of participants with clinically significant laboratory abnormalities
Time Frame
Baseline through 2 years
Title
Number of participants with clinical adverse events at the recommended dose for expansion
Time Frame
Baseline through up to 2 years
Title
Number of participants with clinically significant laboratory abnormalities at recommended dose for expansion
Time Frame
Baseline through 2 years
Secondary Outcome Measure Information:
Title
Number of participants with immune related adverse events
Time Frame
Baseline through 90 days
Title
Single dose: Maximal concentration (Cmax)
Description
PK assessment for PF-07260437
Time Frame
Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3, and Day 1 of each subsequent cycle through end of treatment, up to about 2 years
Title
Time to maximal plasma concentration (Tmax)
Description
PK assessment of PF-07260437
Time Frame
Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3, and Day 1 of each subsequent cycle through end of treatment, up to about 2 years
Title
Single dose: Area Under the Curve (AUClast)
Description
PK assessment of PF-07260437
Time Frame
Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3, and Day 1 of each subsequent cycle through end of treatment, up to about 2 years
Title
Plasma Decay Half-live (t1/2)
Description
PK assessment of PF-07260437
Time Frame
Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3, and Day 1 of each subsequent cycle through end of treatment, up to about 2 years
Title
Area Under the Curve from Time Zero to Extrapolated Infinite Time (AUCinf)
Description
PK assessment of PF-07260437
Time Frame
Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3, and Day 1 of each subsequent cycle through end of treatment, up to about 2 years
Title
Apparent Volume of Distribution (Vz/F)
Description
PK assessment of PF-0260347
Time Frame
Cycle 1 (each cycle is 28 days) Cycle 2, Cycle 3, and Day 1 of each subsequent cycle through end of treatment, up to about 2 years
Title
Accumulation Ratio (Rac)
Description
PK assessment for PF-07260437
Time Frame
Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3 and Day 1 of each subsequent cycle through end of treatment, up to about 2 years
Title
Apparent Oral Clearance (CL/F)
Description
PF assessment of PF-07260437
Time Frame
Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3, and Day 1 of each subsequent cycle through end of treatment, up to about 2 years
Title
Apparent Oral Clearance of Study Drug (CLss/F)
Description
PK assessment for PF-07260437
Time Frame
Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3, and Day of each subsequent cycle through end of treatment, up to about 2 years
Title
Area under the curve at steady state under a dosing interval (AUCss,τ)
Description
PK assessment of PF-07260437
Time Frame
Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3, and Day 1 of each subsequent cycle through end of treatment, up to about 2 years
Title
Maximum Observed Plasma Concentration at Steady State (Cmax,ss)
Description
PK assessment of PF-07260437
Time Frame
Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3, and Day 1 of each subsequent cycle through end of treatment, up to about 2 years
Title
Time to reach maximum Observed Plasma Concentration at Steady State (Tmax,ss)
Description
PK assessment of PF-07260437
Time Frame
Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3, and Day 1 of each subsequent Cycle through end of treatment, up to about 2 years
Title
Minimum Observed Plasma Trough Concentration at Steady State (Cmin,ss)
Description
PK assessment for PF-07260437
Time Frame
Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3 and Day 1 of each subsequent cycle through end of treatment, up to about 2 years.
Title
Incident and titers of anti-body drug antibody against PF-07260437
Description
Immunogenicity of PF-07260437
Time Frame
Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3, and Day 1 of each subsequent cycle through end of treatment, up to about 2 years
Title
Incident and titers of anti-body neutralizing antibody against PF-07260437
Description
Immunogenicity of PF-07260437
Time Frame
Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3, and Day 1 of each subsequent cycle through end of treatment, up to about 2 years
Title
Number of participants with immune related adverse events at the recommended dose for expansion
Time Frame
Baseline through up to 2 years
Title
Duration of response (DOR) in dose expansion
Description
DOR as assessed using RECIST 1.1 and irRECIST
Time Frame
Baseline through up to 2 years or until disease progression
Title
Time to progression (TTP) in dose expansion
Description
TTP as assessed using RECIST 1.1 and irRECIST
Time Frame
Baseline through up to 2 years or until disease progression
Title
Objective response rate (ORR) in dose expansion
Description
ORR as assessed using RECIST 1.1 and irRECIST
Time Frame
Baseline through up to 2 years or until disease progression
Title
Progression free survival (PFS)
Description
PFS as assessed using RECIST 1.1 and irRECIST
Time Frame
Baseline through up to 2 years or until disease progression
Title
Overall survival (OS) in the Expansion Cohorts (Part 2)
Description
Proportion of participants alive
Time Frame
Baseline through up to 2 years
Title
Phenotypes and quantity of tumor infiltrating lymphocytes (TIL) before and after PF-07260437 treatment
Description
Immune Cells assessments from paired biopsies
Time Frame
28 days prior to first dose and 7 days within Cycle 2, Day 15 of PF-07260437

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Part 1: Histological/cytological diagnosis of selected locally advanced or metastatic breast cancer, endometrial cancer and ovarian cancer Part 2A:In second line or more, participants with histological/cytological diagnosis of locally advanced or metastatic HR+ HER2- breast cancer showing high B7-H4 expression Part 2B: In second line or more participants with histological or cytological diagnosis of locally advance or metastatic HR+ Her2- breast cancer or triple negative breast cancer (TNBC) with no biomarker pre-selection Part 2C: In second line or more participants with histological diagnosis of locally advance or metastatic triple negative breast cancer with high B7-H4 expression Thyroid function within normal laboratory range; in participants with abnormal thyroid function if Free T4 is normal and participant is clinically euthyroid, participants is eligible Exclusion Criteria: Participants with any active malignancy within 3 years prior to enrollment Participants with advanced/metastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term (including participants with massive uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and over 50% liver involvement). History of Grade ≥3 immune mediated adverse events (including liver function tests that where considered drug related and cytokine release syndrome) that was considered related to prior immune modulatory therapy (eg, immune checkpoint inhibitors, co stimulatory agents, etc.) and required immunosuppressive therapy within 1 year of treatment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Moffitt Cancer Center at McKinley Campus
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
University of Chicago Comprehensive Cancer Center at Silver Cross Hospital
City
New Lenox
State/Province
Illinois
ZIP/Postal Code
60451
Country
United States
Facility Name
The University of Chicago Medicine Center of Advanced Care Orland Park
City
Orland Park
State/Province
Illinois
ZIP/Postal Code
60462
Country
United States
Facility Name
Montefiore Einstein Center for Cancer Care
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
NEXT Oncology
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Swedish Cancer Institute Edmonds Campus
City
Edmonds
State/Province
Washington
ZIP/Postal Code
98026
Country
United States
Facility Name
Swedish Cancer Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Fred Hutchinson Cancer Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
University of Washington Medical Center - Mountlake
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
Facility Name
Pan American Center for Oncology Trials- Hospital Oncologico
City
Rio Piedras
ZIP/Postal Code
00935
Country
Puerto Rico
Facility Name
Pan American Center for Oncology Trials
City
Rio Piedras
ZIP/Postal Code
00935
Country
Puerto Rico

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing 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.
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=C4431001
Description
To obtain contact information for a study center near you, click here.

Learn more about this trial

A Study of PF-07260437 in Advanced or Metastatic Solid Tumors

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