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
2 other identifiers
interventional
29
2 countries
43
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1 nonsmall-cell-lung-cancer
Started Aug 2021
43 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 9, 2021
CompletedFirst Posted
Study publicly available on registry
May 11, 2021
CompletedStudy Start
First participant enrolled
August 18, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 24, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
October 24, 2023
CompletedApril 3, 2024
April 1, 2024
2.2 years
April 9, 2021
April 2, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
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)
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
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 Outcomes (15)
Single dose Pharmacokinetics (PK) parameter: Maximal concentration (Cmax) in Part 1
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
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
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
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
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
- +10 more secondary outcomes
Study Arms (3)
Dose Escalation (Part 1)
EXPERIMENTALParticipants will receive PF-07257876 at escalating dose levels.
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.
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.
Interventions
CD47-PDL-1 bispecific antibody
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pfizerlead
Study Sites (43)
Mayo Clinic Hospital
Phoenix, Arizona, 85054, United States
Mayo Clinic
Scottsdale, Arizona, 85259, United States
Highlands Oncology Group
Fayetteville, Arkansas, 72703, United States
Highlands Oncology Group
Rogers, Arkansas, 72758, United States
Highlands Oncology Group
Springdale, Arkansas, 72762, United States
Hoag Hospital Irvine
Irvine, California, 92618, United States
The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate
Los Angeles, California, 90025, United States
Keck Hospital of USC
Los Angeles, California, 90033, United States
Keck School of Medicine of USC
Los Angeles, California, 90033, United States
LAC+USC Medical Center
Los Angeles, California, 90033, United States
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
Hoag Memorial Hospital Presbyterian
Newport Beach, California, 92663, United States
Keck Hospital of USC Pasadena
Pasadena, California, 91105, United States
The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate (Emergency Back-Up Only)
Santa Monica, California, 90404, United States
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224, United States
Mayo Clinic Rochester
Rochester, Minnesota, 55905, United States
Siteman Cancer Center - St Peters
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center - West County
Creve Coeur, Missouri, 63141, United States
Siteman Cancer Center-North County
Florissant, Missouri, 63031, United States
Barnes-Jewish Hospital
St Louis, Missouri, 63110, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Washington University
St Louis, Missouri, 63110, United States
Siteman Cancer Center - South County
St Louis, Missouri, 63129, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Duke Cancer Institute
Durham, North Carolina, 27710, United States
UPMC Hillman Cancer Center - Camp Hill
Camp Hill, Pennsylvania, 17011, United States
UPMC Hillman Cancer Center - Carlisle
Carlisle, Pennsylvania, 17015, United States
UPMC Hillman Cancer Center Erie
Erie, Pennsylvania, 16505, United States
UPMC Pinnacle - Community Osteopathic / Medical Sciences Pavilion (MSP)
Harrisburg, Pennsylvania, 17109, United States
UPMC Pinnacle - Ortenzio Cancer Center (OCC)
Mechanicsburg, Pennsylvania, 17050, United States
Magee-Womens Hospital of UPMC
Pittsburgh, Pennsylvania, 15213, United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
UPMC Shadyside Hospital
Pittsburgh, Pennsylvania, 15232, United States
UPMC Memorial
York, Pennsylvania, 17408, United States
Rhode Island Hospital
Providence, Rhode Island, 02903, United States
The Miriam Hospital
Providence, Rhode Island, 02906, United States
Virginia Cancer Specialists
Fairfax, Virginia, 22031, United States
Seattle Cancer Care Alliance
Seattle, Washington, 98109, United States
Hospital Universitari Vall d'Hebron
Barcelona, Barcelona [barcelona], 08035, Spain
Hospital General Universitario Gregorio Marañon
Madrid, Madrid, Comunidad de, 28009, Spain
Hospital Universitario 12 de Octubre
Madrid, Madrid, Comunidad de, 28041, Spain
Hospital Clinico de Valencia
Valencia, Valenciana, Comunitat, 46010, Spain
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Pfizer CT.gov Call Center
Pfizer
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
April 9, 2021
First Posted
May 11, 2021
Study Start
August 18, 2021
Primary Completion
October 24, 2023
Study Completion
October 24, 2023
Last Updated
April 3, 2024
Record last verified: 2024-04
Data Sharing
- IPD Sharing
- Will not share
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.