Clinical Trials /

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

NCT04881045

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: C4401001
  • NCT ID: NCT04881045

Conditions

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

Interventions

DrugSynonymsArms
PF-07257876Dose Escalation (Part 1)

Purpose

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 Arms

NameTypeDescriptionInterventions
Dose Escalation (Part 1)ExperimentalParticipants will receive PF-07257876 at escalating dose levels.
  • PF-07257876
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.
  • PF-07257876
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.
  • PF-07257876

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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)
Safety Issue:
Description: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

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Pfizer

Trial 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

Last Updated

July 28, 2021