A Study to Learn About the Study Medicine Called PF-08046876 in People With Advanced Solid Tumors

Not Applicable

Not yet recruiting

• Conditions: Advanced/Metastatic Solid Tumors; Bladder Cancer; Urothelial Carcinoma; Advanced Non-Small Cell Lung Cancer; Carcinoma, Non Small Cell Lung; Carcinoma, Squamous Cell of Head and Neck; Head and Neck Cancer; Esophageal Cancer; Gastroesophageal Junction Adenocarcinoma; Esophageal Squamous Cell Carcinoma
• Interventions: Drug: PF-08046876

• Registration Number: NCT07090499
• Lead Sponsor: Pfizer

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-07
• Study First Submitted: 2025-07-21
• Study First Submitted QC: 2025-07-21
• Last Update Submitted: 2025-07-21
• Study First Posted: 2025-07-29
• Last Update Posted: 2025-07-29
• Study Start: 2025-08-07
• Primary Completion: 2028-08-19
• Study Completion: 2029-08-19

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 310

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 1 Dose Escalation	PF-08046876	Different groups of participants will receive different doses and/or schedules of the study drug
Part 2 Dose Optimization	PF-08046876	Participants will be randomized to 2 dosing regimens deemed to be safe in Part 1
Part 2 Dose Expansion	PF-08046876	Participants in tumor-specific groups will receive 1 dosing regimen deemed to be safe in Part 1

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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).
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.
Progression Free Survival (PFS)	From Baseline to date of first disease progression or death (approximately 2 Years)	PFS as defined per RECIST 1.1.
Overall Survival (OS)	From baseline to up to 3 years	OS defined as the time until death due to any cause.
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.
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.
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.