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

Ovarian Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04881045
• Other study ID #: C4401001
• Secondary ID: 2022-003338-38
• Status: Completed
• Phase: Phase 1
• Start date: August 18, 2021
• Est. completion date: October 24, 2023

Study information

• Verified date: April 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: October 24, 2023
• Est. primary completion date: October 24, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Squamous Cell
• Lung Neoplasms
• Non-Small Cell Lung Cancer
• Ovarian Cancer
• Ovarian Neoplasms
• Squamous Cell Carcinoma of Head and Neck
• Squamous Cell Carcinoma of the Head and Neck

Intervention

Biological:
• PF-07257876
CD47-PDL-1 bispecific antibody

Locations

Country	Name	City	State
Spain	Hospital Universitari Vall d'Hebron	Barcelona	Barcelona [barcelona]
Spain	Hospital General Universitario Gregorio Marañon	Madrid	Madrid, Comunidad DE
Spain	Hospital Universitario 12 de Octubre	Madrid	Madrid, Comunidad DE
Spain	Hospital Clinico de Valencia	Valencia	Valenciana, Comunitat
United States	UPMC Hillman Cancer Center - Camp Hill	Camp Hill	Pennsylvania
United States	UPMC Hillman Cancer Center - Carlisle	Carlisle	Pennsylvania
United States	Siteman Cancer Center - West County	Creve Coeur	Missouri
United States	Duke Cancer Institute	Durham	North Carolina
United States	UPMC Hillman Cancer Center Erie	Erie	Pennsylvania
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Highlands Oncology Group	Fayetteville	Arkansas
United States	Siteman Cancer Center-North County	Florissant	Missouri
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	UPMC Pinnacle - Community Osteopathic / Medical Sciences Pavilion (MSP)	Harrisburg	Pennsylvania
United States	Hoag Hospital Irvine	Irvine	California
United States	Mayo Clinic Jacksonville	Jacksonville	Florida
United States	Keck Hospital of USC	Los Angeles	California
United States	Keck School of Medicine of USC	Los Angeles	California
United States	LAC+USC Medical Center	Los Angeles	California
United States	The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	UPMC Pinnacle - Ortenzio Cancer Center (OCC)	Mechanicsburg	Pennsylvania
United States	Hoag Memorial Hospital Presbyterian	Newport Beach	California
United States	Keck Hospital of USC Pasadena	Pasadena	California
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	Magee-Womens Hospital of UPMC	Pittsburgh	Pennsylvania
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	UPMC Shadyside Hospital	Pittsburgh	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	The Miriam Hospital	Providence	Rhode Island
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	Highlands Oncology Group	Rogers	Arkansas
United States	Barnes-Jewish Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center - South County	Saint Louis	Missouri
United States	Washington University	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Siteman Cancer Center - St Peters	Saint Peters	Missouri
United States	The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate (Emergency Back-Up Only)	Santa Monica	California
United States	Mayo Clinic	Scottsdale	Arizona
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Highlands Oncology Group	Springdale	Arkansas
United States	UPMC Memorial	York	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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
Primary	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
Primary	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	Single dose Pharmacokinetics (PK) parameter: Maximal concentration (Cmax) in Part 1	Maximum observed plasma concentration of PF-07257876 (Cmax)	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
Secondary	Single dose PK parameter: Time to maximal plasma concentration (Tmax) in Part 1	Time to maximal observed plasma concentration of PF-07257876 (Tmax)	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
Secondary	Single dose PK parameter: Area under the Curve (AUClast) in Part 1	Area under the concentration-time curve from time zero to the last quantifiable time point prior to the next dose.	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
Secondary	Multiple dose PK parameter: Maximal concentration (Cmax, ss) in Part 1	Maximum observed steady state plasma concentration of PF-07257876 (Cmax, ss)	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
Secondary	Multiple dose PK parameter: Time to maximal plasma concentration (Tmax, ss) in Part 1	Time to reach Maximum Observed Steady State Plasma Concentration (Tmax,ss).	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
Secondary	Multiple dose PK parameter: Area under the Curve (AUCtau, ss) in Part 1	Area Under the curve within one dose interval at steady state (AUCtau,ss)	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
Secondary	Immunogenicity of PF-07257876	Incidence, titers, and duration (if data permit) of antidrug antibodies (ADA) and neutralizing antibodies against 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
Secondary	Intratumor T cell levels	Immune biomarker levels in archival biopsies and/or de novo and on-treatment tumor biopsies.	Baseline through Cycle 2 Day 15 (each cycle is 28 days)
Secondary	Intratumor PD-L1 expression	PD-L1 expression levels in pretreatment tumor biopsies	Baseline through Cycle 2 Day 15 (each cycle is 28 days)
Secondary	ORR in Dose Escalation (Part 1)	Tumor response assessment based on RECIST 1.1	Baseline through up to 2 years or until disease progression
Secondary	Duration of response (DOR)	DOR as assessed using RECIST 1.1	Baseline through up to 2 years or until disease progression
Secondary	Progression free survival (PFS)	PFS as assessed using RECIST 1.1	Baseline through up to 2 years or until disease progression
Secondary	Time to progression (TTP)	TTP as assessed using RECIST 1.1	Baseline through up to 2 years or until disease progression
Secondary	Lowest concentration (Ctrough) reached before the next dose is administered in Part 2	PK assessment for PF-07257876	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
Secondary	Overall Survival (OS) in the Expansion Cohorts (Part 2)	Proportion of patients alive	Baseline through up to 2 years or until disease progression

External Links

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