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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04881045
Recruitment Status : Recruiting
First Posted : May 11, 2021
Last Update Posted : April 1, 2022
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief 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 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.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Squamous Cell Carcinoma of the Head and Neck Ovarian Cancer Biological: PF-07257876 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 18, 2021
Estimated Primary Completion Date : July 12, 2024
Estimated Study Completion Date : July 12, 2024


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




Primary Outcome Measures :
  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 Outcome Measures :
  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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04881045


Contacts
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Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
Show Show 39 study locations
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT04881045    
Other Study ID Numbers: C4401001
First Posted: May 11, 2021    Key Record Dates
Last Update Posted: April 1, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
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
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Ovarian Neoplasms
Squamous Cell Carcinoma of Head and Neck
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neoplasms, Squamous Cell
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Head and Neck Neoplasms