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

Breast Neoplasms Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05067972
• Other study ID #: C4431001
• Status: Terminated
• Phase: Phase 1
• Start date: October 7, 2021
• Est. completion date: October 17, 2023

Study information

• Verified date: April 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: October 17, 2023
• Est. primary completion date: October 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Endometrial Neoplasms
• Neoplasms
• Ovarian Neoplasms

Intervention

Drug:
• PF-07260437
B7-H4 x CD3 bi-specific mAb

Diagnostic Test:
• B7-H4 IHC
B7-H4 expression

Locations

Country	Name	City	State
Puerto Rico	Pan American Center for Oncology Trials	Rio Piedras
Puerto Rico	Pan American Center for Oncology Trials, LLC	Rio Piedras
Puerto Rico	Pan American Center for Oncology Trials- Hospital Oncologico	Rio Piedras
United States	Montefiore Einstein Center for Cancer Care	Bronx	New York
United States	University of Chicago Medical Center	Chicago	Illinois
United States	City of Hope (City of Hope National Medical Center, City of Hope Medical Center)	Duarte	California
United States	Swedish Cancer Institute Edmonds Campus	Edmonds	Washington
United States	University of Chicago Comprehensive Cancer Center at Silver Cross Hospital	New Lenox	Illinois
United States	The University of Chicago Medicine Center of Advanced Care Orland Park	Orland Park	Illinois
United States	NEXT Oncology	San Antonio	Texas
United States	Fred Hutchinson Cancer Center	Seattle	Washington
United States	Swedish Cancer Institute	Seattle	Washington
United States	University of Washington Medical Center - Mountlake	Seattle	Washington
United States	Moffitt Cancer Center	Tampa	Florida
United States	Moffitt Cancer Center at McKinley Campus	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Baseline through 28 days after first dose
Primary	Number of participants with adverse events		Baseline through up to 2 years
Primary	Number of participants with clinically significant laboratory abnormalities		Baseline through 2 years
Primary	Number of participants with clinical adverse events at the recommended dose for expansion		Baseline through up to 2 years
Primary	Number of participants with clinically significant laboratory abnormalities at recommended dose for expansion		Baseline through 2 years
Secondary	Number of participants with immune related adverse events		Baseline through 90 days
Secondary	Single dose: Maximal concentration (Cmax)	PK assessment for PF-07260437	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
Secondary	Time to maximal plasma concentration (Tmax)	PK assessment of PF-07260437	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
Secondary	Single dose: Area Under the Curve (AUClast)	PK assessment of PF-07260437	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
Secondary	Plasma Decay Half-live (t1/2)	PK assessment of PF-07260437	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
Secondary	Area Under the Curve from Time Zero to Extrapolated Infinite Time (AUCinf)	PK assessment of PF-07260437	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
Secondary	Apparent Volume of Distribution (Vz/F)	PK assessment of PF-0260347	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
Secondary	Accumulation Ratio (Rac)	PK assessment for PF-07260437	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
Secondary	Apparent Oral Clearance (CL/F)	PF assessment of PF-07260437	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
Secondary	Apparent Oral Clearance of Study Drug (CLss/F)	PK assessment for PF-07260437	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
Secondary	Area under the curve at steady state under a dosing interval (AUCss,t)	PK assessment of PF-07260437	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
Secondary	Maximum Observed Plasma Concentration at Steady State (Cmax,ss)	PK assessment of PF-07260437	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
Secondary	Time to reach maximum Observed Plasma Concentration at Steady State (Tmax,ss)	PK assessment of PF-07260437	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
Secondary	Minimum Observed Plasma Trough Concentration at Steady State (Cmin,ss)	PK assessment for PF-07260437	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.
Secondary	Incident and titers of anti-body drug antibody against PF-07260437	Immunogenicity of PF-07260437	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
Secondary	Incident and titers of anti-body neutralizing antibody against PF-07260437	Immunogenicity of PF-07260437	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
Secondary	Number of participants with immune related adverse events at the recommended dose for expansion		Baseline through up to 2 years
Secondary	Duration of response (DOR) in dose expansion	DOR as assessed using RECIST 1.1 and irRECIST	Baseline through up to 2 years or until disease progression
Secondary	Time to progression (TTP) in dose expansion	TTP as assessed using RECIST 1.1 and irRECIST	Baseline through up to 2 years or until disease progression
Secondary	Objective response rate (ORR) in dose expansion	ORR as assessed using RECIST 1.1 and irRECIST	Baseline through up to 2 years or until disease progression
Secondary	Progression free survival (PFS)	PFS as assessed using RECIST 1.1 and irRECIST	Baseline through up to 2 years or until disease progression
Secondary	Overall survival (OS) in the Expansion Cohorts (Part 2)	Proportion of participants alive	Baseline through up to 2 years
Secondary	Phenotypes and quantity of tumor infiltrating lymphocytes (TIL) before and after PF-07260437 treatment	Immune Cells assessments from paired biopsies	28 days prior to first dose and 7 days within Cycle 2, Day 15 of PF-07260437

External Links

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