Study to Test the Safety and Tolerability of PF-07257876 in Participants With Selected Advanced Tumors.

A PHASE 1 DOSE ESCALATION AND EXPANSION STUDY EVALUATING THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTITUMOR ACTIVITY OF PF-07257876 IN PATIENTS WITH ADVANCED OR METASTATIC TUMORS

This is a first-in-human, Phase 1, open label, multicenter, multiple dose, dose escalation and dose expansion study intended to evaluate the safety, pharmacokinetic, pharmacodynamic and potential clinical benefit of PF-07257876, a CD47-PD-L1 bispecific antibody, in participants with selected advanced or metastatic tumors for whom no standard therapy is available. The study contains 2 parts, single agent Dose Escalation (Part 1) to determine the recommended dose of PF-07257876, followed by Dose Expansion (Part 2) in selected tumor types at the recommended dose.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer; Non-Small Cell Lung Cancer; Squamous Cell Carcinoma of the Head and Neck
• Intervention / Treatment: Biological: PF-07257876

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona [barcelona]
    • Barcelona, Barcelona [barcelona], Spain, 08035
      • Hospital Universitari Vall d'Hebron
  • Madrid, Comunidad de
    • Madrid, Madrid, Comunidad de, Spain, 28041
      • Hospital Universitario 12 de Octubre
    • Madrid, Madrid, Comunidad de, Spain, 28009
      • Hospital General Universitario Gregorio Marañon
  • Valenciana, Comunitat
    • Valencia, Valenciana, Comunitat, Spain, 46010
      • Hospital Clinico de Valencia
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Hospital
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group
    • Rogers, Arkansas, United States, 72758
      • Highlands Oncology Group
    • Springdale, Arkansas, United States, 72762
      • Highlands Oncology Group
  • California
    • Irvine, California, United States, 92618
      • Hoag Hospital Irvine
    • Los Angeles, California, United States, 90033
      • USC/Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90033
      • Keck Hospital of USC
    • Los Angeles, California, United States, 90033
      • LAC+USC Medical Center
    • Los Angeles, California, United States, 90033
      • Keck School of Medicine of USC
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate
    • Newport Beach, California, United States, 92663
      • Hoag Memorial Hospital Presbyterian
    • Pasadena, California, United States, 91105
      • Keck Hospital of USC Pasadena
    • Santa Monica, California, United States, 90404
      • The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate (Emergency Back-Up Only)
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • Missouri
    • City of Saint Peters, Missouri, United States, 63376
      • Siteman Cancer Center - St Peters
    • Creve Coeur, Missouri, United States, 63141
      • Siteman Cancer Center - West County
    • Florissant, Missouri, United States, 63031
      • Siteman Cancer Center-North County
    • St Louis, Missouri, United States, 63110
      • Barnes-Jewish Hospital
    • St Louis, Missouri, United States, 63110
      • Washington University
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • St Louis, Missouri, United States, 63129
      • Siteman Cancer Center - South County
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Institute
  • Pennsylvania
    • Camp Hill, Pennsylvania, United States, 17011
      • UPMC Hillman Cancer Center - Camp Hill
    • Carlisle, Pennsylvania, United States, 17015
      • UPMC Hillman Cancer Center - Carlisle
    • Erie, Pennsylvania, United States, 16505
      • UPMC Hillman Cancer Center Erie
    • Harrisburg, Pennsylvania, United States, 17109
      • UPMC Pinnacle - Community Osteopathic / Medical Sciences Pavilion (MSP)
    • Mechanicsburg, Pennsylvania, United States, 17050
      • UPMC Pinnacle - Ortenzio Cancer Center (OCC)
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15213
      • Magee-Womens Hospital of UPMC
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Shadyside Hospital
    • York, Pennsylvania, United States, 17408
      • UPMC Memorial
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hospital
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histological/cytological diagnosis of selected advanced or metastatic tumor
• Prior treatment with PD-1 (Programmed cell death 1) or PD-L1 (programmed death-ligand 1) in NSCLC and SCCHN or platinum-based therapy in Ovarian cancer
• Confirmed radiographic progression of disease
• PD-L1 IHC positivity ≥1%
• Have ≥1 measurable lesion as defined by RECIST 1.1 that has not been previously irradiated
• Eastern Cooperative Oncology Group performance status 0-1
• Adequate hematologic, renal and liver functions
• Resolved acute effects of any prior therapy
• Participants in Part 1 must be able to provide archival tumor tissue collected within the prior 6 months or consent to undergo a fresh biopsy during screening. Participants enrolled to the MTD (Maximum Tolerated Dose) cohort in Part 1 must consent to mandatory paired pre-treatment and on-treatment biopsies. Participants in Part 2 must consent to a pre-treatment biopsy and a subset of patients must consent to a paired on-study biopsy as well until the Sponsor deems an adequate number have been received.

Exclusion Criteria:

• Participants with known brain metastasis larger than 4 cm or that is symptomatic. New brain metastases detected at screening. Participants with previously diagnosed brain metastases are eligible if they have completed treatment and recovered from acute effects prior to study entry.
• Abnormal neurological assessment by investigator
• Other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ
• Major surgery or radiation therapy within 4 weeks prior to planned first dose
• Last systemic anti-cancer therapy within 28 days or 5 half-lives (whichever is shorter) prior to planned first dose (6 weeks for mitomycin C or nitrosoureas)
• Active bleeding disorder in the past 6 months prior to first dose
• History of clinically significant severe immune mediated adverse event that was considered related to prior immune modulatory therapy and required immunosuppressive therapy (other than hormone replacement therapy)
• History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (ie, bronchiolitis obliterans, cryptogenic organizing pneumonia), evidence of active pneumonitis on screening chest CT(computer tomography) scan
• Anticoagulation with vitamin K antagonists or factor Xa inhibitors is not allowed
• Treatment with chronic systemic corticosteroids or other immunosuppressive medications
• Participation in other studies involving investigational drug(s) within 4 weeks prior to planned first dose
• Active, uncontrolled bacterial, fungal, or viral infection, Hepatitis B, Hepatitis C, or Human immunodeficiency virus (HIV) infection
• Active COVID-19/SARS-CoV2
• Pregnant or breastfeeding female participant
• Organ transplant requiring immunosuppressive treatment or prior allogeneic bone marrow or hematopoietic stem cell transplant
• Significant cardiac or pulmonary conditions or events within previous 6 months

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation (Part 1); Participants will receive PF-07257876 at escalating dose levels.	Biological: PF-07257876; CD47-PDL-1 bispecific antibody
Experimental: Dose Expansion (Part 2) - Cohort 1 (NSCLC); Participants with non-small cell lung cancer (NSCLC) will receive PF-07257876 at the recommended dose from Part 1.	Biological: PF-07257876; CD47-PDL-1 bispecific antibody
Experimental: Dose Expansion (Part 2) - Cohort 2 (SCCHN); Participants with squamous cell carcinoma of the head and neck (SCCHN) will receive PF-07257876 at the recommended dose from Part 1.	Biological: PF-07257876; CD47-PDL-1 bispecific antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events (AEs)	AEs characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 5.0), timing, seriousness, and relationship to study therapy.	Baseline through up to 2 years
Number of participants with clinically significant laboratory abnormalities	Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.	Baseline through up to 2 years
Number of participants with dose limiting toxicities (DLTs) in Dose Escalation (Part 1)	DLTs will be evaluated during Cycle 1 (a cycle is 28 days) in Part 1. The number of DLTs will be used to determine the optimal dose	Baseline through end of Cycle 1 (each cycle is 28 days)
Objective response rate (ORR) in the Expansion cohorts (Part 2)	Tumor response based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	Baseline through up to 2 years or until disease progression

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DOR)	DOR as assessed using RECIST 1.1	Baseline through up to 2 years or until disease progression
Time to progression (TTP)	TTP as assessed using RECIST 1.1	Baseline through up to 2 years or until disease progression
Progression free survival (PFS)	PFS as assessed using RECIST 1.1	Baseline through up to 2 years or until disease progression
Single dose Pharmacokinetics (PK) parameter: Maximal concentration (Cmax) in Part 1	Maximum observed plasma concentration of PF-07257876 (Cmax)	Cycle 1, Cycle 2, Cycle 3, Cycle 4, and pre-dose on Day 1 at Cycle 5 and every third cycle thereafter (all cycles are 28 days) and at End of Treatment, up to 2 years
Single dose PK parameter: Time to maximal plasma concentration (Tmax) in Part 1	Time to maximal observed plasma concentration of PF-07257876 (Tmax)	Cycle 1, Cycle 2, Cycle 3, Cycle 4, and pre-dose on Day 1 at Cycle 5 and every third cycle thereafter (all cycles are 28 days) and at End of Treatment, up to 2 years
Single dose PK parameter: Area under the Curve (AUClast) in Part 1	Area under the concentration-time curve from time zero to the last quantifiable time point prior to the next dose.	Cycle 1, Cycle 2, Cycle 3, Cycle 4, and pre-dose on Day 1 at Cycle 5 and every third cycle thereafter (all cycles are 28 days) and at End of Treatment, up to 2 years
Multiple dose PK parameter: Maximal concentration (Cmax, ss) in Part 1	Maximum observed steady state plasma concentration of PF-07257876 (Cmax, ss)	Cycle 1, Cycle 2, Cycle 3, Cycle 4, and pre-dose on Day 1 at Cycle 5 and every third cycle thereafter (all cycles are 28 days) and at End of Treatment, up to 2 years
Multiple dose PK parameter: Time to maximal plasma concentration (Tmax, ss) in Part 1	Time to reach Maximum Observed Steady State Plasma Concentration (Tmax,ss).	Cycle 1, Cycle 2, Cycle 3, Cycle 4, and pre-dose on Day 1 at Cycle 5 and every third cycle thereafter (all cycles are 28 days) and at End of Treatment, up to 2 years
Multiple dose PK parameter: Area under the Curve (AUCtau, ss) in Part 1	Area Under the curve within one dose interval at steady state (AUCtau,ss)	Cycle 1, Cycle 2, Cycle 3, Cycle 4, and pre-dose on Day 1 at Cycle 5 and every third cycle thereafter (all cycles are 28 days) and at End of Treatment, up to 2 years
Immunogenicity of PF-07257876	Incidence, titers, and duration (if data permit) of antidrug antibodies (ADA) and neutralizing antibodies against PF-07257876	Cycle 1, Cycle 2, Cycle 3, Cycle 4, and pre-dose on Day 1 at Cycle 5 and every third cycle thereafter (all cycles are 28 days) and at End of Treatment, up to 2 years
Intratumor T cell levels	Immune biomarker levels in archival biopsies and/or de novo and on-treatment tumor biopsies.	Baseline through Cycle 2 Day 15 (each cycle is 28 days)
Intratumor PD-L1 expression	PD-L1 expression levels in pretreatment tumor biopsies	Baseline through Cycle 2 Day 15 (each cycle is 28 days)
ORR in Dose Escalation (Part 1)	Tumor response assessment based on RECIST 1.1	Baseline through up to 2 years or until disease progression
Lowest concentration (Ctrough) reached before the next dose is administered in Part 2	PK assessment for PF-07257876	Pre-dose on Day 1 at Cycles 1, 2, 3, 4, 5 and every third cycle thereafter (each cycle is 28 days) and End of Treatment visit, up to 2 years
Overall Survival (OS) in the Expansion Cohorts (Part 2)	Proportion of patients alive	Baseline through up to 2 years or until disease progression

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): August 18, 2021
• Primary Completion (Actual): October 24, 2023
• Study Completion (Actual): October 24, 2023

Study Registration Dates

• First Submitted: April 9, 2021
• First Submitted That Met QC Criteria: May 5, 2021
• First Posted (Actual): May 11, 2021

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Lung Cancer; immunotherapy; NSCLC; Non-small cell lung cancer; metastatic cancer; solid tumor; Ovarian Cancer; advanced cancer; advanced solid tumor; metastatic solid tumor; Head and Neck cancer; SCCHN; Squamous cell carcinoma of the head and neck; PD-L1 (Programmed death-ligand 1); CD47 (cluster of differentiation 47); macrophage checkpoint inhibitor; Squamous cell head and neck cancer
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Respiratory Tract Diseases; Neoplasms by Histologic Type; Genital Diseases, Female; Lung Diseases; Endocrine Gland Neoplasms; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplastic Processes; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Carcinoma; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Squamous Cell; Pathological Conditions, Signs and Symptoms; Squamous Cell Carcinoma of Head and Neck; Lung Neoplasms; Ovarian Neoplasms; Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung; Head and Neck Neoplasms
• Other Study ID Numbers: C4401001; 2022-003338-38 (EudraCT Number)

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