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.
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
Drug | Synonyms | Arms |
---|
PF-07257876 | | Dose 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
Name | Type | Description | Interventions |
---|
Dose Escalation (Part 1) | Experimental | Participants will receive PF-07257876 at escalating dose levels. | |
Dose Expansion (Part 2) - Cohort 1 (NSCLC) | Experimental | 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) | Experimental | Participants with squamous cell carcinoma of the head and neck (SCCHN) will receive PF-07257876 at the recommended dose from Part 1. | |
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