Study to Test the Safety and Tolerability of PF-07257876 in Participants With Selected Advanced Tumors.
- Conditions
- Squamous Cell Carcinoma of the Head and NeckOvarian CancerNon-Small Cell Lung Cancer
- Interventions
- Biological: PF-07257876
- Registration Number
- NCT04881045
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 29
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation (Part 1) PF-07257876 Participants will receive PF-07257876 at escalating dose levels. Dose Expansion (Part 2) - Cohort 1 (NSCLC) PF-07257876 Participants 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) PF-07257876 Participants with squamous cell carcinoma of the head and neck (SCCHN) will receive PF-07257876 at the recommended dose from Part 1.
- Primary Outcome Measures
Name Time Method Number of participants with adverse events (AEs) 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.
Number of participants with clinically significant laboratory abnormalities Baseline through up to 2 years Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.
Objective response rate (ORR) in the Expansion cohorts (Part 2) Baseline through up to 2 years or until disease progression Tumor response based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Number of participants with dose limiting toxicities (DLTs) in Dose Escalation (Part 1) 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
- Secondary Outcome Measures
Name Time Method 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 Area under the concentration-time curve from time zero to the last quantifiable time point prior to the next dose.
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 Maximum observed steady state plasma concentration of PF-07257876 (Cmax, ss)
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 Time to reach Maximum Observed Steady State Plasma Concentration (Tmax,ss).
Duration of response (DOR) Baseline through up to 2 years or until disease progression DOR as assessed using RECIST 1.1
Progression free survival (PFS) Baseline through up to 2 years or until disease progression PFS as assessed using RECIST 1.1
Time to progression (TTP) Baseline through up to 2 years or until disease progression TTP as assessed using RECIST 1.1
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 Time to maximal observed plasma concentration of PF-07257876 (Tmax)
Intratumor PD-L1 expression Baseline through Cycle 2 Day 15 (each cycle is 28 days) PD-L1 expression levels in pretreatment tumor biopsies
ORR in Dose Escalation (Part 1) Baseline through up to 2 years or until disease progression Tumor response assessment based on RECIST 1.1
Immunogenicity of 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 Incidence, titers, and duration (if data permit) of antidrug antibodies (ADA) and neutralizing antibodies against PF-07257876
Intratumor T cell levels 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.
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 Maximum observed plasma concentration of PF-07257876 (Cmax)
Multiple dose PK parameter: Area under the Curve (AUCtau, 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 Area Under the curve within one dose interval at steady state (AUCtau,ss)
Lowest concentration (Ctrough) reached before the next dose is administered in Part 2 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
Overall Survival (OS) in the Expansion Cohorts (Part 2) Baseline through up to 2 years or until disease progression Proportion of patients alive
Trial Locations
- Locations (41)
Siteman Cancer Center - St Peters
🇺🇸Saint Peters, Missouri, United States
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Madrid, Comunidad DE, Spain
The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate (Emergency Back-Up Only)
🇺🇸Santa Monica, California, United States
John Theurer Cancer Center at Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Highlands Oncology Group
🇺🇸Springdale, Arkansas, United States
Siteman Cancer Center-North County
🇺🇸Florissant, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Barcelona [barcelona], Spain
Mayo Clinic Jacksonville
🇺🇸Jacksonville, Florida, United States
UPMC Hillman Cancer Center - Carlisle
🇺🇸Carlisle, Pennsylvania, United States
UPMC Hillman Cancer Center Erie
🇺🇸Erie, Pennsylvania, United States
Siteman Cancer Center - West County
🇺🇸Creve Coeur, Missouri, United States
UPMC Pinnacle - Ortenzio Cancer Center (OCC)
🇺🇸Mechanicsburg, Pennsylvania, United States
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Madrid, Comunidad DE, Spain
Hospital Clinico de Valencia
🇪🇸Valencia, Valenciana, Comunitat, Spain
Hoag Hospital Irvine
🇺🇸Irvine, California, United States
The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate
🇺🇸Los Angeles, California, United States
Keck School of Medicine of USC
🇺🇸Los Angeles, California, United States
Keck Hospital of USC
🇺🇸Los Angeles, California, United States
UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
LAC+USC Medical Center
🇺🇸Los Angeles, California, United States
USC/Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Hoag Memorial Hospital Presbyterian
🇺🇸Newport Beach, California, United States
Magee-Womens Hospital of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC Shadyside Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC Memorial
🇺🇸York, Pennsylvania, United States
Keck Hospital of USC Pasadena
🇺🇸Pasadena, California, United States
Siteman Cancer Center - South County
🇺🇸Saint Louis, Missouri, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
UPMC Hillman Cancer Center - Camp Hill
🇺🇸Camp Hill, Pennsylvania, United States
UPMC Pinnacle - Community Osteopathic / Medical Sciences Pavilion (MSP)
🇺🇸Harrisburg, Pennsylvania, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Duke Cancer Institute
🇺🇸Durham, North Carolina, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Mayo Clinic
🇺🇸Scottsdale, Arizona, United States
Barnes-Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
The Miriam Hospital
🇺🇸Providence, Rhode Island, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States