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OpenTrials
Completed

NCT Number: NCT04881045

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

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Key information

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

PF-07257876

Biological

CD47-PDL-1 bispecific antibody

Primary outcomes

  1. 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)

    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

  2. Number of participants with adverse events (AEs)

    Time frame: Baseline through up to 2 years

    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.

  3. Number of participants with clinically significant laboratory abnormalities

    Time frame: Baseline through up to 2 years

    Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.

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

    Time frame: Baseline through up to 2 years or until disease progression

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

Secondary outcomes

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

    Time frame: 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

    Maximum observed plasma concentration of PF-07257876 (Cmax)

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

    Time frame: 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

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

  3. Single dose PK parameter: Area under the Curve (AUClast) in Part 1

    Time frame: 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

    Area under the concentration-time curve from time zero to the last quantifiable time point prior to the next dose.

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

    Time frame: 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

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

  5. Multiple dose PK parameter: Time to maximal plasma concentration (Tmax, ss) in Part 1

    Time frame: 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

    Time to reach Maximum Observed Steady State Plasma Concentration (Tmax,ss).

  6. Multiple dose PK parameter: Area under the Curve (AUCtau, ss) in Part 1

    Time frame: 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

    Area Under the curve within one dose interval at steady state (AUCtau,ss)

  7. Immunogenicity of PF-07257876

    Time frame: 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

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

  8. Intratumor T cell levels

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

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

  9. Intratumor PD-L1 expression

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

    PD-L1 expression levels in pretreatment tumor biopsies

  10. ORR in Dose Escalation (Part 1)

    Time frame: Baseline through up to 2 years or until disease progression

    Tumor response assessment based on RECIST 1.1

  11. Duration of response (DOR)

    Time frame: Baseline through up to 2 years or until disease progression

    DOR as assessed using RECIST 1.1

  12. Progression free survival (PFS)

    Time frame: Baseline through up to 2 years or until disease progression

    PFS as assessed using RECIST 1.1

  13. Time to progression (TTP)

    Time frame: Baseline through up to 2 years or until disease progression

    TTP as assessed using RECIST 1.1

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

    Time frame: 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

    PK assessment for PF-07257876

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

    Time frame: Baseline through up to 2 years or until disease progression

    Proportion of patients alive

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study 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

Important dates

Study start
2021
Primary completion
2023
Study completion
2023
First posted
May 11, 2021
Registry last updated
Jun 2, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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