Clinical trial NCT04881045: Study to Test the Safety and Tolerability of PF-07257876 in Participants With Selected Advanced Tumors.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-Small Cell Lung Cancer
Squamous Cell Carcinoma of the Head and Neck
Ovarian Cancer
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
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2021-05-11
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Number of participants with dose limiting toxicities (DLTs) in Dose Escalation (Part 1)
timeFrame: Baseline through end of Cycle 1 (each cycle is 28 days)
measure: Number of participants with adverse events (AEs)
timeFrame: Baseline through up to 2 years
measure: Number of participants with clinically significant laboratory abnormalities
timeFrame: Baseline through up to 2 years
measure: Objective response rate (ORR) in the Expansion cohorts (Part 2)
timeFrame: Baseline through up to 2 years or until disease progression
Secondary outcomes:
measure: Single dose Pharmacokinetics (PK) parameter: Maximal concentration (Cmax) in Part 1
timeFrame: 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
measure: Single dose PK parameter: Time to maximal plasma concentration (Tmax) in Part 1
timeFrame: 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
measure: Single dose PK parameter: Area under the Curve (AUClast) in Part 1
timeFrame: 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
measure: Multiple dose PK parameter: Maximal concentration (Cmax, ss) in Part 1
timeFrame: 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
measure: Multiple dose PK parameter: Time to maximal plasma concentration (Tmax, ss) in Part 1
timeFrame: 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
measure: Multiple dose PK parameter: Area under the Curve (AUCtau, ss) in Part 1
timeFrame: 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
measure: Immunogenicity of PF-07257876
timeFrame: 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
measure: Intratumor T cell levels
timeFrame: Baseline through Cycle 2 Day 15 (each cycle is 28 days)
measure: Intratumor PD-L1 expression
timeFrame: Baseline through Cycle 2 Day 15 (each cycle is 28 days)
measure: ORR in Dose Escalation (Part 1)
timeFrame: Baseline through up to 2 years or until disease progression
measure: Duration of response (DOR)
timeFrame: Baseline through up to 2 years or until disease progression
measure: Progression free survival (PFS)
timeFrame: Baseline through up to 2 years or until disease progression
measure: Time to progression (TTP)
timeFrame: Baseline through up to 2 years or until disease progression
measure: Lowest concentration (Ctrough) reached before the next dose is administered in Part 2
timeFrame: 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
measure: Overall Survival (OS) in the Expansion Cohorts (Part 2)
timeFrame: Baseline through up to 2 years or until disease progression
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Rogers
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Springdale
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Irvine
country: United States
facility: Hoag Hospital Irvine
state: California
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate
state: California
city: Los Angeles
country: United States
facility: Keck Hospital of USC
state: California
city: Los Angeles
country: United States
facility: Keck School of Medicine of USC
state: California
city: Los Angeles
country: United States
facility: LAC+USC Medical Center
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: Pasadena
country: United States
facility: Keck Hospital of USC Pasadena
state: California
city: Santa Monica
country: United States
facility: The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate (Emergency Back-Up Only)
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Creve Coeur
country: United States
facility: Siteman Cancer Center - West County
state: Missouri
city: Florissant
country: United States
facility: Siteman Cancer Center-North County
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center - South County
state: Missouri
city: Saint Peters
country: United States
facility: Siteman Cancer Center - St Peters
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: Durham
country: United States
facility: Duke Cancer Institute
state: North Carolina
city: Camp Hill
country: United States
facility: UPMC Hillman Cancer Center - Camp Hill
state: Pennsylvania
city: Carlisle
country: United States
facility: UPMC Hillman Cancer Center - Carlisle
state: Pennsylvania
city: Erie
country: United States
facility: UPMC Hillman Cancer Center Erie
state: Pennsylvania
city: Harrisburg
country: United States
facility: UPMC Pinnacle - Community Osteopathic / Medical Sciences Pavilion (MSP)
state: Pennsylvania
city: Mechanicsburg
country: United States
facility: UPMC Pinnacle - Ortenzio Cancer Center (OCC)
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital of UPMC
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Shadyside Hospital
state: Pennsylvania
city: York
country: United States
facility: UPMC Memorial
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Barcelona [barcelona]
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
state: Madrid, Comunidad DE
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
state: Madrid, Comunidad DE
city: Valencia
country: Spain
facility: Hospital Clinico de Valencia
state: Valenciana, Comunitat
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: