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

Pfizer41 sites in 2 countries29 target enrollmentAugust 18, 2021

ConditionsNon-Small Cell Lung Cancer Squamous Cell Carcinoma of the Head and Neck Ovarian Cancer

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Non-Small Cell Lung Cancer
Sponsor: Pfizer
Enrollment: 29
Locations: 41
Primary Endpoint: Number of participants with adverse events (AEs)
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

August 18, 2021

End Date

October 24, 2023

Last Updated

2 years ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Pfizer

Responsible Party

Sponsor

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

Outcomes

Primary Outcomes

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.

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.

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

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

Secondary Outcomes

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)
Duration of response (DOR)(Baseline through up to 2 years or until disease progression)
Progression free survival (PFS)(Baseline through up to 2 years or until disease progression)
Time to progression (TTP)(Baseline through up to 2 years or until disease progression)
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)
Intratumor PD-L1 expression(Baseline through Cycle 2 Day 15 (each cycle is 28 days))
ORR in Dose Escalation (Part 1)(Baseline through up to 2 years or until disease progression)
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)
Intratumor T cell levels(Baseline through Cycle 2 Day 15 (each cycle is 28 days))
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)
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)
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)
Overall Survival (OS) in the Expansion Cohorts (Part 2)(Baseline through up to 2 years or until disease progression)