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

NCT05067972 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: C4431001
• Study Type: interventional
• Target: 30
• Locations: 2 countries
• Sites: 15

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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• Number of Participants With Immune-Related Adverse Events (irAEs)

  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

  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)

  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)

  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)

  Day 1 pre-dose, 1, 4, 8, 24, 48 and 168 hours post-dose, till Day 15 pre-dose in Cycle 1

Study Arms (4)

Monotherapy dose escalation (Part 1)

EXPERIMENTAL

Participants will receive PF-07260437

Drug: PF-07260437

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

EXPERIMENTAL

Participants will receive PF-07260437

Drug: PF-07260437; Diagnostic Test: B7-H4 IHC

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

EXPERIMENTAL

Participants will receive PF-07260437

Drug: PF-07260437; Diagnostic Test: B7-H4 IHC

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

EXPERIMENTAL

Participants will receive PF07260437

Drug: PF-07260437; Diagnostic Test: B7-H4 IHC

Interventions

PF-07260437 DRUG

B7-H4 x CD3 bi-specific mAb

Also known as: B7-H4

Dose Expansion (Part 2A) - Tumor specific Arm A; Dose Expansion (Part 2B) - Tumor specific Arm B; Dose Expansion (Part 2C) - Tumor specific Arm C; Monotherapy dose escalation (Part 1)

B7-H4 IHC DIAGNOSTIC_TEST

B7-H4 expression

Dose Expansion (Part 2A) - Tumor specific Arm A; Dose Expansion (Part 2B) - Tumor specific Arm B; Dose Expansion (Part 2C) - Tumor specific Arm C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (15)

City of Hope (City of Hope National Medical Center, City of Hope Medical Center)

Duarte, California, 91010, United States

Location

Moffitt Cancer Center at McKinley Campus

Tampa, Florida, 33612, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

University of Chicago Comprehensive Cancer Center at Silver Cross Hospital

New Lenox, Illinois, 60451, United States

Location

The University of Chicago Medicine Center of Advanced Care Orland Park

Orland Park, Illinois, 60462, United States

Location

Montefiore Einstein Center for Cancer Care

The Bronx, New York, 10461, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

Swedish Cancer Institute Edmonds Campus

Edmonds, Washington, 98026, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

University of Washington Medical Center - Mountlake

Seattle, Washington, 98195, United States

Location

Pan American Center for Oncology Trials, LLC

Rio Piedras, 00935, Puerto Rico

Location

Pan American Center for Oncology Trials- Hospital Oncologico

Rio Piedras, 00935, Puerto Rico

Location

Pan American Center for Oncology Trials

Rio Piedras, 00935, Puerto Rico

Location

Related Links

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

MeSH Terms

Conditions

Ovarian Neoplasms; Endometrial Neoplasms; Breast Neoplasms

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

The decision to terminate the study was made on 27 Jul 2023, due to strategic reasons. The multiple dose PK samples were not collected due to dose interruption or discontinuation. By the time of study termination, Part 2 of the study has not been initiated. Therefore, no data have been collected for Part 2 and corresponding endpoints were not reported.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2021
• First Posted: October 5, 2021
• Study Start: October 7, 2021
• Primary Completion: October 17, 2023
• Study Completion: October 17, 2023
• Last Updated: May 6, 2025
• Results First Posted: May 6, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (12); PR (3)