Non-Small Cell Lung Cancer, Ovarian Cancer, Squamous Cell Carcinoma of the Head and Neck
Conditions
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
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.
Interventions
BIOLOGICALPF-07257876
CD47-PDL-1 bispecific antibody
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with dose limiting toxicities (DLTs) in Dose Escalation (Part 1) | 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 |
| Number of participants with adverse events (AEs) | 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 | 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) | Baseline through up to 2 years or until disease progression | Tumor response based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Maximum observed plasma concentration of PF-07257876 (Cmax) |
| 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 | Time to maximal observed plasma concentration of PF-07257876 (Tmax) |
| 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 | Area under the concentration-time curve from time zero to the last quantifiable time point prior to the next dose. |
| 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 | Maximum observed steady state plasma concentration of PF-07257876 (Cmax, ss) |
| 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 | Time to reach Maximum Observed Steady State Plasma Concentration (Tmax,ss). |
| 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 | Area Under the curve within one dose interval at steady state (AUCtau,ss) |
| 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 | Incidence, titers, and duration (if data permit) of antidrug antibodies (ADA) and neutralizing antibodies against PF-07257876 |
| Intratumor T cell levels | Baseline through Cycle 2 Day 15 (each cycle is 28 days) | Immune biomarker levels in archival biopsies and/or de novo and on-treatment tumor biopsies. |
| Intratumor PD-L1 expression | Baseline through Cycle 2 Day 15 (each cycle is 28 days) | PD-L1 expression levels in pretreatment tumor biopsies |
| ORR in Dose Escalation (Part 1) | Baseline through up to 2 years or until disease progression | Tumor response assessment based on RECIST 1.1 |
| Duration of response (DOR) | Baseline through up to 2 years or until disease progression | DOR as assessed using RECIST 1.1 |
| Progression free survival (PFS) | Baseline through up to 2 years or until disease progression | PFS as assessed using RECIST 1.1 |
| Time to progression (TTP) | Baseline through up to 2 years or until disease progression | TTP as assessed using RECIST 1.1 |
| 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 | PK assessment for PF-07257876 |
| Overall Survival (OS) in the Expansion Cohorts (Part 2) | Baseline through up to 2 years or until disease progression | Proportion of patients alive |
Countries
Spain, United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed