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

Phase 1

Terminated

• Conditions: Breast Neoplasms; Endometrial Neoplasms; Ovarian Neoplasms
• Interventions: Drug: PF-07260437; Diagnostic Test: B7-H4 IHC

• Registration Number: NCT05067972
• Lead Sponsor: Pfizer

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2021-09-24
• Study First Submitted QC: 2021-09-24
• Study First Posted: 2021-10-05
• Study Start: 2021-10-07
• Primary Completion: 2023-10-17
• Study Completion: 2023-10-17
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-19
• Last Update Posted: 2024-04-22

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 30

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Monotherapy dose escalation (Part 1)	PF-07260437	Participants will receive PF-07260437
Dose Expansion (Part 2A) - Tumor specific Arm A	PF-07260437	Participants will receive PF-07260437
Dose Expansion (Part 2A) - Tumor specific Arm A	B7-H4 IHC	Participants will receive PF-07260437
Dose Expansion (Part 2B) - Tumor specific Arm B	PF-07260437	Participants will receive PF-07260437
Dose Expansion (Part 2B) - Tumor specific Arm B	B7-H4 IHC	Participants will receive PF-07260437
Dose Expansion (Part 2C) - Tumor specific Arm C	PF-07260437	Participants will receive PF07260437
Dose Expansion (Part 2C) - Tumor specific Arm C	B7-H4 IHC	Participants will receive PF07260437

Primary Outcome Measures

Name	Time	Method
Number of participants with clinical adverse events at the recommended dose for expansion	Baseline through up to 2 years
Number of participants with adverse events	Baseline through up to 2 years
Number of participants with dose limiting toxicities (DLTs) in Dose escalation	Baseline through 28 days after first dose	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 clinically significant laboratory abnormalities	Baseline through 2 years
Number of participants with clinically significant laboratory abnormalities at recommended dose for expansion	Baseline through 2 years

Secondary Outcome Measures

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

Trial Locations

Locations (15)

Swedish Cancer Institute; 🇺🇸 Seattle, Washington, United States

University of Washington Medical Center - Mountlake; 🇺🇸 Seattle, Washington, United States

Pan American Center for Oncology Trials- Hospital Oncologico; 🇵🇷 Rio Piedras, Puerto Rico

Swedish Cancer Institute Edmonds Campus; 🇺🇸 Edmonds, Washington, United States

Pan American Center for Oncology Trials, LLC; 🇵🇷 Rio Piedras, Puerto Rico

NEXT Oncology; 🇺🇸 San Antonio, Texas, United States

Fred Hutchinson Cancer Center; 🇺🇸 Seattle, Washington, United States

Moffitt Cancer Center at McKinley Campus; 🇺🇸 Tampa, Florida, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

City of Hope (City of Hope National Medical Center, City of Hope Medical Center); 🇺🇸 Duarte, California, 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

University of Chicago Medical Center; 🇺🇸 Chicago, Illinois, United States

Pan American Center for Oncology Trials; 🇵🇷 Rio Piedras, Puerto Rico

Montefiore Einstein Center for Cancer Care; 🇺🇸 Bronx, New York, United States