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Non-Small Cell Lung CancerPhase 1NCT04881045

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

A Phase 1 study testing PF-07257876 in people with Non-Small Cell Lung Cancer and Squamous Cell Carcinoma of the Head and Neck, run by Pfizer at 43 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
PF-07257876
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
43 sitesin 2 countries
Study dates
18 Aug 2021to 24 Oct 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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
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  • 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

Trial locations and contacts

43 sites in 2 countries.

43 sites in 2 countries

United States39 sites

  • UPMC Hillman Cancer Center - Camp Hill

    Camp Hill, Pennsylvania, 17011

  • UPMC Hillman Cancer Center - Carlisle

    Carlisle, Pennsylvania, 17015

  • Siteman Cancer Center - St Peters

    City of Saint Peters, Missouri, 63376

  • Siteman Cancer Center - West County

    Creve Coeur, Missouri, 63141

  • Duke Cancer Institute

    Durham, North Carolina, 27710

  • UPMC Hillman Cancer Center Erie

    Erie, Pennsylvania, 16505

  • Virginia Cancer Specialists

    Fairfax, Virginia, 22031

  • Highlands Oncology Group

    Fayetteville, Arkansas, 72703

  • Siteman Cancer Center-North County

    Florissant, Missouri, 63031

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • John Theurer Cancer Center at Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • UPMC Pinnacle - Community Osteopathic / Medical Sciences Pavilion (MSP)

    Harrisburg, Pennsylvania, 17109

  • Hoag Hospital Irvine

    Irvine, California, 92618

  • Mayo Clinic Jacksonville

    Jacksonville, Florida, 32224

  • The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate

    Los Angeles, California, 90025

  • Keck Hospital of USC

    Los Angeles, California, 90033

  • Keck School of Medicine of USC

    Los Angeles, California, 90033

  • LAC+USC Medical Center

    Los Angeles, California, 90033

  • USC/Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • UPMC Pinnacle - Ortenzio Cancer Center (OCC)

    Mechanicsburg, Pennsylvania, 17050

  • Hoag Memorial Hospital Presbyterian

    Newport Beach, California, 92663

  • Keck Hospital of USC Pasadena

    Pasadena, California, 91105

  • Mayo Clinic Hospital

    Phoenix, Arizona, 85054

  • Magee-Womens Hospital of UPMC

    Pittsburgh, Pennsylvania, 15213

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • UPMC Shadyside Hospital

    Pittsburgh, Pennsylvania, 15232

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • The Miriam Hospital

    Providence, Rhode Island, 02906

  • Mayo Clinic Rochester

    Rochester, Minnesota, 55905

  • Highlands Oncology Group

    Rogers, Arkansas, 72758

  • The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate (Emergency Back-Up Only)

    Santa Monica, California, 90404

  • Mayo Clinic

    Scottsdale, Arizona, 85259

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

  • Highlands Oncology Group

    Springdale, Arkansas, 72762

  • Barnes-Jewish Hospital

    St Louis, Missouri, 63110

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Washington University

    St Louis, Missouri, 63110

  • Siteman Cancer Center - South County

    St Louis, Missouri, 63129

  • UPMC Memorial

    York, Pennsylvania, 17408

Other trials in United States

Spain4 sites

  • Hospital Universitari Vall d'Hebron

    Barcelona, Barcelona [barcelona], 08035

  • Hospital General Universitario Gregorio Marañon

    Madrid, Madrid, Comunidad de, 28009

  • Hospital Universitario 12 de Octubre

    Madrid, Madrid, Comunidad de, 28041

  • Hospital Clinico de Valencia

    Valencia, Valenciana, Comunitat, 46010

Other trials in Spain

About this study

Official title: 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.

Being tested
PF-07257876
Keywords
PD-L1 (Programmed death-ligand 1), CD47 (cluster of differentiation 47), immunotherapy, macrophage checkpoint inhibitor, advanced solid tumor, metastatic solid tumor, Ovarian Cancer, Lung Cancer, Non-small cell lung cancer, Head and Neck cancer, SCCHN, NSCLC, solid tumor, advanced cancer, metastatic cancer, Squamous cell carcinoma of the head and neck, Squamous cell head and neck cancer
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Squamous Cell Carcinoma of Head and Neck, Ovarian Neoplasms, Neoplasm Metastasis, Lung Neoplasms, Head and Neck Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PF-07257876Biological

    CD47-PDL-1 bispecific antibody

Study groups in NCT04881045
Study groupRoleWhat they receive
Dose Escalation (Part 1)ExperimentalParticipants will receive PF-07257876 at escalating dose levels.
Receives: Biological: PF-07257876
Dose Expansion (Part 2) - Cohort 1 (NSCLC)ExperimentalParticipants with non-small cell lung cancer (NSCLC) will receive PF-07257876 at the recommended dose from Part 1.
Receives: Biological: PF-07257876
Dose Expansion (Part 2) - Cohort 2 (SCCHN)ExperimentalParticipants with squamous cell carcinoma of the head and neck (SCCHN) will receive PF-07257876 at the recommended dose from Part 1.
Receives: Biological: PF-07257876

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Baseline through end of Cycle 1 (each cycle is 28 days)

  2. 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.

    Measured: Baseline through up to 2 years

  3. 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.

    Measured: Baseline through up to 2 years

  4. Objective response rate (ORR) in the Expansion cohorts (Part 2)

    Tumor response based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

    Measured: Baseline through up to 2 years or until disease progression

Secondary outcomes (15)

  1. Single dose Pharmacokinetics (PK) parameter: Maximal concentration (Cmax) in Part 1

    Maximum observed plasma concentration of PF-07257876 (Cmax)

    Measured: 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

  2. Single dose PK parameter: Time to maximal plasma concentration (Tmax) in Part 1

    Time to maximal observed plasma concentration of PF-07257876 (Tmax)

    Measured: 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

  3. 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.

    Measured: 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

  4. Multiple dose PK parameter: Maximal concentration (Cmax, ss) in Part 1

    Maximum observed steady state plasma concentration of PF-07257876 (Cmax, ss)

    Measured: 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

  5. 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).

    Measured: 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

  6. 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)

    Measured: 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

  7. Immunogenicity of PF-07257876

    Incidence, titers, and duration (if data permit) of antidrug antibodies (ADA) and neutralizing antibodies against PF-07257876

    Measured: 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

  8. Intratumor T cell levels

    Immune biomarker levels in archival biopsies and/or de novo and on-treatment tumor biopsies.

    Measured: Baseline through Cycle 2 Day 15 (each cycle is 28 days)

  9. Intratumor PD-L1 expression

    PD-L1 expression levels in pretreatment tumor biopsies

    Measured: Baseline through Cycle 2 Day 15 (each cycle is 28 days)

  10. ORR in Dose Escalation (Part 1)

    Tumor response assessment based on RECIST 1.1

    Measured: Baseline through up to 2 years or until disease progression

  11. Duration of response (DOR)

    DOR as assessed using RECIST 1.1

    Measured: Baseline through up to 2 years or until disease progression

  12. Progression free survival (PFS)

    PFS as assessed using RECIST 1.1

    Measured: Baseline through up to 2 years or until disease progression

  13. Time to progression (TTP)

    TTP as assessed using RECIST 1.1

    Measured: Baseline through up to 2 years or until disease progression

  14. Lowest concentration (Ctrough) reached before the next dose is administered in Part 2

    PK assessment for PF-07257876

    Measured: 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

  15. Overall Survival (OS) in the Expansion Cohorts (Part 2)

    Proportion of patients alive

    Measured: Baseline through up to 2 years or until disease progression

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 May 2021
  2. Study start18 Aug 2021
  3. Primary completion24 Oct 2023
  4. Study completion24 Oct 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04881045
Sponsor's protocol ID
C4401001
Other IDs
2022-003338-38
Status last verified
Oct 2025
First submitted
9 Apr 2021
Last updated
2 Jun 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PF-07257876 in people with Non-Small Cell Lung Cancer and Squamous Cell Carcinoma of the Head and Neck, run by Pfizer at 43 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 43 sites in United States, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with dose limiting toxicities (DLTs) in Dose Escalation (Part 1) (time frame: Baseline through end of Cycle 1 (each cycle is 28 days)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04881045.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2026.

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