Advanced/Metastatic Solid Tumors, Advanced Non-Small Cell Lung Cancer, Bladder Cancer, Carcinoma, Non Small Cell Lung, Carcinoma, Squamous Cell of Head and Neck, Esophageal Adenocarcinoma, Esophageal Cancer, Esophageal Squamous Cell Carcinoma, Gastroesophageal Junction Adenocarcinoma, Head and Neck Cancer, Pancreatic Adenocarcinoma, Pancreatic Cancer, Urothelial Carcinoma
Conditions
Keywords
B6C, integrin beta 6, ADC, antibody drug conjugate, bladder cancer, urothelial carcinoma, non-small cell lung cancer, NSCLC, head and neck cancer, HNSCC, SCCHN, esophageal cancer, EC, esophageal squamous cell carcinoma, gastroesophageal junction adenocarcinoma, pancreatic cancer, PDAC, pancreatic adenocarcinoma, esophageal adenocarcinoma, lung adenocarcinoma, lung squamous cell carcinoma, integrin alpha-v beta-6 receptor, ITGB6
Brief summary
The purpose of the study is to explore the safety and effects of the study drug (PF-08046876) in people diagnosed with advanced cancer of the bladder, lung, head and neck, esophagus, or pancreas. PF-08046876 is an investigational anticancer therapy called an 'antibody drug conjugate' or 'ADC'. ADCs are anticancer drugs designed to stick to cancer cells and kill them. The study drug will be given to participants through a needle in a vein (intravenous infusion). This study includes multiple parts. In the first part of the study, there will be different groups of people receiving different doses of the study drug. The study may also test different schedules.
Interventions
DRUGPF-08046876
Intravenous administration
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age or older * Advanced cancer of the bladder, lung, head and neck, esophagus, or pancreas * Measurable disease * ECOG Performance status 0-1 * Part 1: progression or relapse following standard treatments * Part 2: maximum of 2 prior lines of systemic therapy in the advanced setting * Resolution of acute effects of prior anticancer therapy to baseline or Grade 1 * Consent to submit required pre-treatment tumor tissue as medically feasible
Exclusion criteria
* Received prior treatment with an antibody drug conjugate with a camptothecin-class payload (e.g. sacituzumab govitecan, trastuzumab deruxtecan ) * Active anorexia, nausea or vomiting, and/or signs of intestinal obstruction meeting protocol exclusion * Pulmonary disease meeting protocol exclusion * Other unacceptable abnormalities as defined by protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment Emergent Adverse Events (TEAEs) estimated during the Adverse Events (AE) evaluation | Start of treatment up to 30 days after last dose or start of new anticancer therapy (whichever occurs first) | AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy dose modifications. |
| Part 1: Number of Participants With Dose-limiting Toxicities (DLTs): Monotherapy | Baseline to end of DLT evaluation period | Occurrence of DLTs as defined by the protocol |
| Part 1: Recommended Monotherapy Dose for Expansion | Baseline to 30 days post last study drug administration | RDE will be based on cumulative safety, preliminary antitumor activity and pharmacokinetics findings |
| Part 2: Recommended Phase 2 Dose | Baseline to 30 days post last study drug administration | RP2D will be determined based on the cumulative safety, preliminary anti tumor activity and Pharmacokinetics findings. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Neutralizing Antibodies (NAb) | Baseline to approximately 30 days after last dose of study drug | To evaluate the immunogenicity of PF-08046876. |
| Percent change of immune cells within tumors based on multiplex immunofluorescence | Baseline through 4-7 weeks after first dose of study drug | This measure will assess changes in the presence or activation of immune cells in the tumor microenvironment using RNA and/or Immunohistochemistry (IHC) assays. |
| Duration of Response (DOR) | From the date of the first objective response to the date of disease progression or death (approximately 2 years) | DOR as defined per RECIST 1.1. |
| Pharmacokinetics (PK): Maximum Observed Serum Concentration (Cmax) | Baseline to approximately 30 days after last dose of study drug | Evaluate the single and multiple dose PK of PF-08048676. |
| Overall Survival (OS) | From baseline to up to 3 years | OS defined as the time until death due to any cause. |
| Objective Response Rate (ORR) | Baseline until the date of the first documentation of disease progression, death, or start of new anticancer therapy (approximately 2 years) | ORR defined as per Response Evaluation Criteria in Solid Tumors (RECIST v1.1). |
| Progression Free Survival (PFS) | From Baseline to date of first disease progression or death (approximately 2 Years) | PFS as defined per RECIST 1.1. |
| PK: Time to Reach Maximum Observed Plasma Concentration (Tmax) | Baseline to approximately 30 days after last dose of study drug | Evaluate the single and multiple dose PK of PF-08048676. |
| PK: Area Under the Curve (AUC) from Time Zero to Last Quantifiable Concentration (AUClast) | Baseline to approximately 30 days after last dose of study drug | Evaluate the single and multiple dose PK of PF-08048676. |
| Incidence of Anti-Drug Antibody (ADA) | Baseline to approximately 30 days after last dose of study drug | To evaluate the immunogenicity of PF-08046876. |
Countries
Canada, China, Puerto Rico, Spain, United Kingdom, United States
Contacts
CONTACTPfizer CT.gov Call Center
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed