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

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

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.

Study Overview

• Status: Terminated
• Conditions: Breast Neoplasms; Ovarian Neoplasms; Endometrial Neoplasms
• Intervention / Treatment: Drug: PF-07260437; Diagnostic test: B7-H4 IHC

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Puerto Rico
  • Rio Piedras, Puerto Rico, 00935
    • Pan American Center for Oncology Trials
  • Rio Piedras, Puerto Rico, 00935
    • Pan American Center for Oncology Trials- Hospital Oncologico
  • Rio Piedras, Puerto Rico, 00935
    • Pan American Center for Oncology Trials, LLC
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope (City of Hope National Medical Center, City Of Hope Medical Center)
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center at McKinley Campus
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University Of Chicago Medical Center
    • New Lenox, Illinois, United States, 60451
      • University of Chicago Comprehensive Cancer Center at Silver Cross Hospital
    • Orland Park, Illinois, United States, 60462
      • The University of Chicago Medicine Center of Advanced Care Orland Park
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Einstein Center for Cancer Care
  • Texas
    • San Antonio, Texas, United States, 78229
      • NEXT Oncology
  • Washington
    • Edmonds, Washington, United States, 98026
      • Swedish Cancer Institute Edmonds Campus
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Center
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center - Mountlake

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Monotherapy dose escalation (Part 1); Participants will receive PF-07260437	Drug: PF-07260437; B7-H4 x CD3 bi-specific mAb; Other Names: B7-H4
Experimental: Dose Expansion (Part 2A) - Tumor specific Arm A; Participants will receive PF-07260437	Drug: PF-07260437; B7-H4 x CD3 bi-specific mAb; Other Names: B7-H4; Diagnostic test: B7-H4 IHC; B7-H4 expression
Experimental: Dose Expansion (Part 2B) - Tumor specific Arm B; Participants will receive PF-07260437	Drug: PF-07260437; B7-H4 x CD3 bi-specific mAb; Other Names: B7-H4; Diagnostic test: B7-H4 IHC; B7-H4 expression
Experimental: Dose Expansion (Part 2C) - Tumor specific Arm C; Participants will receive PF07260437	Drug: PF-07260437; B7-H4 x CD3 bi-specific mAb; Other Names: B7-H4; Diagnostic test: B7-H4 IHC; B7-H4 expression

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose-Limiting Toxicities (DLTs) in Dose Escalation - Part 1	Any of the following treatment-related adverse events (AEs) occurring during the DLT observation period were classified as DLTs: Hematological DLTs: neutropenia Grade (G) 4, febrile neutropenia, ≥G3 for >7d (days), G3 with infection; thrombocytopenia G4, G3 with bleeding or requiring platelet transfusion; anemia G4, G3 requiring blood transfusion. Non-hematologic: hepatic toxicity; ≥G3 fatigue for ≥5d, ≥G3 nausea/vomiting or diarrhea for ≥3d, ≥G3 cytokine release syndrome (CRS) of any duration/QTcF prolongation/anaphylaxis, G5 AE without clear reason; immune-related (ir)AE: ≥G4 irAEs/colitis, G3/4 non-infectious pneumonitis, G2 pneumonitis not resolved to ≤G1 within 3d of the initiation of max supportive care. Severity of AEs were graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, with the exception of CRS, which were graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading for CRS.	The first dose of the study intervention (C1D1) through Day 28 for participants without a priming dose or through Day 42 for participants with a priming dose.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) - Part 1	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. TEAE was defined as any AE that occurred from first dose of study intervention to either last dose of study treatment + 90 days, start of new anti-cancer therapy, or completion in study as determined by disposition, whichever was earliest. A serious AE (SAE) was defined as any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, persistent disability/incapacity, or was a congenital anomaly/birth defect. AEs were graded by the investigator according to CTCAE v5.0.	Baseline (Day 1 of dosing ) through 4 week follow-up, up to 35.1 weeks
Number of Participants With Clinically Significant Laboratory Abnormalities - Part 1	Laboratory parameters included: hematology (hemoglobin, hematocrit, red blood cell, platelet and white blood cell count, neutrophils, eosinophils, monocytes, basophils and lymphocytes), chemistry (blood urea nitrogen, creatinine, sodium, potassium, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein and serum pregnancy test [for all female participants]) and urine (urine pregnancy test [for all female participants]). Clinical significance of laboratory parameters was determined at the investigator's discretion.	Baseline through up to 35.1 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Immune-Related Adverse Events (irAEs)	irAEs included gastrointestinal (ie, diarrhea/colitis), dermatological (ie, rash), pulmonary (ie, pneumonitis), hepatic (ie, liver test elevation), renal (ie, creatinine increased), cardiac (ie, myocarditis), endocrine (ie, endocrine disorder), and other toxicities.	Day 1 up to 90 days after the last dose of study intervention (Day 246 [C9D15]), up to approximately 336 days
Number of Participants by Categories of Anti-Drug Antibody (ADA) Against PF-07260437	Number of participants with positive ADA against PF-07257876 were summarized for each treatment arm. A participant had treatment-induced ADA response if he/she had negative or missing ADA at baseline and ≥1 post-treatment ADA positive titer. A participant had treatment-boosted ADA response if he/she had positive titer at baseline and a ratio of ≥4 in titer (dilution) to baseline in ≥1 post-treatment sample.	On Day 1 of Cycle 1, 2, 3. From Cycle 4 onwards: collection on Day 1 of every 3 cycles (C4D1, C7D1, etc.) until end-of-treatment visit, up to 35.1 weeks.
Single Dose: Maximal Concentration (Cmax)	Maximum observed serum concentration following single dose of PF-07260437. The multiple dose PK samples were not collected due to dose interruption or discontinuation. The PK sampling schedule was designed to evaluate the dosing interval of 2 weeks. Since the 100/300/800 group received the second dose (300 ug) only 1 week after the first dose. The PK parameters were not calculable.	Day 1 pre-dose, 1, 4, 8, 24, 48 and 168 hours post-dose, till Day 15 pre-dose in Cycle 1
Single Dose: Area Under the Curve (AUCtau)	Area under the plasma concentration-time profile from time 0 to time tau (τ), the dosing interval following single dose of PF-07260437. The multiple dose PK samples were not collected due to dose interruption or discontinuation. The PK sampling schedule was designed to evaluate the dosing interval of 2 weeks. Since the 100/300/800 group received the second dose (300 ug) only 1 week after the first dose. The PK parameters were not calculable.	Day 1 pre-dose, 1, 4, 8, 24, 48 and 168 hours post-dose, till Day 15 pre-dose in Cycle 1
Single Dose: Time to Maximal Plasma Concentration (Tmax)	Time to maximal plasma concentration following single dose of PF-07260437. The multiple dose PK samples were not collected due to dose interruption or discontinuation. The PK sampling schedule was designed to evaluate the dosing interval of 2 weeks. Since the 100/300/800 group received the second dose (300 ug) only 1 week after the first dose. The PK parameters were not calculable.	Day 1 pre-dose, 1, 4, 8, 24, 48 and 168 hours post-dose, till Day 15 pre-dose in Cycle 1

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2021
• Primary Completion (Actual): October 17, 2023
• Study Completion (Actual): October 17, 2023

Study Registration Dates

• First Submitted: September 24, 2021
• First Submitted That Met QC Criteria: September 24, 2021
• First Posted (Actual): October 5, 2021

Study Record Updates

• Last Update Posted (Actual): May 6, 2025
• Last Update Submitted That Met QC Criteria: April 17, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Breast Cancer; Ovarian Cancer; Endometrial Carcinoma; Endometrium Cancer; Endometrial Cancer; Breast Carcinoma; Cancer of the Breast; Breast Tumors; Malignant Neoplasm of Breast; Cancer of Endometrium; Cancer of the Endometrium; Carcinoma of Endometrium; Neoplasms, Endometrial; Cancer of Breast; Neoplasms, Ovarian; Human Mammary Carcinoma; Cancer of Ovary; Cancer of the Ovary; Ovary Cancer; Ovary Neoplasms; Malignant Tumor of Breast
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Breast Diseases; Uterine Neoplasms; Neoplasms; Ovarian Neoplasms; Breast Neoplasms; Endometrial Neoplasms
• Other Study ID Numbers: C4431001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No