Advanced/Metastatic Solid TumorsPhase 1NCT07090499
A Study to Learn About the Study Medicine Called PF-08046876 in People With Advanced Solid Tumors
A Phase 1 study testing PF-08046876, Pembrolizumab and Cisplatin in people with Advanced/Metastatic Solid Tumors and Bladder Cancer, run by Pfizer at 31 sites in 6 countries.
Trial 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'. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced/Metastatic Solid Tumors, Bladder Cancer, Urothelial Carcinoma
- What is being tested?
- PF-08046876, Pembrolizumab and Cisplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 540 participants
- Where
- 31 sitesin 6 countries
- Study dates
- 20 Aug 2025to 8 Jul 2029
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- Part 3: advanced cancer of the lung or bladder, prior treatment requirements vary by combination therapy group
- Resolution of acute effects of prior anticancer therapy to baseline or Grade 1
- Consent to submit required pre-treatment tumor tissue as medically feasible
Who cannot join
- 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
- Part 3: Meet contraindications of combination products per protocol and/or local labels
Trial locations and contacts
31 sites in 6 countries. Contact the study team or a site near you to ask about taking part.
31 sites in 6 countries
United States21 sites, 21 recruiting
- Recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02115
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
- Recruiting
The University of Texas MD Anderson Cancer Center - Conroe
Conroe, Texas, 77384
- Recruiting
City of Hope National Medical Center
Duarte, California, 91010
- Recruiting
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
- Recruiting
The University of Texas, MD Anderson Cancer Center - West Houston
Houston, Texas, 77079
- Recruiting
City of Hope at Irvine Lennar
Irvine, California, 92618
- Recruiting
The University of Texas, MD Anderson Cancer Center - League City
League City, Texas, 77573
- Not yet recruiting
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095
- Not yet recruiting
UCLA Department of Medicine-Hematology/Oncology
Los Angeles, California, 90095
- Recruiting
Sarah Cannon Research Institute - Pharmacy
Nashville, Tennessee, 37203
- Recruiting
SCRI Oncology Partners
Nashville, Tennessee, 37203
- Recruiting
Smilow Cancer Hospital - Yale New Haven Health
New Haven, Connecticut, 06510
- Recruiting
Yale - New Haven Hospital - Yale Cancer Center
New Haven, Connecticut, 06510
- Recruiting
Smilow Cancer Hospital Phase 1 Unit
New Haven, Connecticut, 06511
- Recruiting
Dana-Farber Cancer Institute - Chestnut Hill
Newton, Massachusetts, 02467
- Recruiting
NEXT Oncology
San Antonio, Texas, 78229
- Not yet recruiting
Santa Monica UCLA Medical Center & Orthopaedic Hospital
Santa Monica, California, 90404
- Not yet recruiting
UCLA Hematology/Oncology - Santa Monica
Santa Monica, California, 90404
- Recruiting
The University of Texas, MD Anderson Cancer Center - Sugar Land
Sugar Land, Texas, 77478
- Recruiting
Smilow Cancer Hospital - Trumbull
Trumbull, Connecticut, 06611
Canada3 sites, 3 recruiting
- Recruiting
McGill University Health Centre
Montreal, Quebec, H4A 3J1
- Recruiting
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 1Z5
- Recruiting
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9
Spain3 sites, 3 recruiting
- Recruiting
Hospital Universitari Vall d'Hebron
Barcelona, Barcelona [barcelona], 08035
- Recruiting
Hospital Universitario 12 de Octubre
Madrid, Madrid, Comunidad de, 28041
- Recruiting
Hospital Universitario Fundación Jiménez Díaz
Madrid, 28040
United Kingdom2 sites, 2 recruiting
- Not yet recruiting
Barts Cancer Centre at St. Bartholomew's Hospital; Queen Mary University of London
London, EC1A 7BE
- Recruiting
The Christie NHS Foundation Trust
Manchester, M20 4BX
China1 site, 1 recruiting
- Not yet recruiting
Hunan Cancer Hospital
Changsha, Hunan, 410013
Puerto Rico1 site, 1 recruiting
- Recruiting
Pan American Center for Oncology Trials, LLC
Rio Piedras, 00935
About this study
Official title: A Phase 1 Open-label Study to Investigate PF-08046876 in Adult Participants With Advanced Solid Tumors.
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. In the second part of the study, groups of people will receive the study drug in dosing regimens deemed to be safe in Part 1. In the third part of the study, people will receive the study drug together with other anti-cancer medicines.
- 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
- Being tested
- PF-08046876, Pembrolizumab, Cisplatin, Carboplatin
- 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
- Medical subject headings
- Urinary Bladder Neoplasms, Carcinoma, Transitional Cell, Carcinoma, Non-Small-Cell Lung, Squamous Cell Carcinoma of Head and Neck, Head and Neck Neoplasms, Esophageal Neoplasms, Esophageal Squamous Cell Carcinoma, Adenocarcinoma Of Esophagus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PF-08046876Drug
Intravenous administration
PembrolizumabCombination product
Intravenous administration
CisplatinCombination product
Intravenous administration
CarboplatinCombination product
Intravenous administration
| Study group | Role | What they receive |
|---|---|---|
| Part 1 Dose Escalation | Experimental | Different groups of participants will receive different doses and/or schedules of the study drug Receives: Drug: PF-08046876 |
| Part 2 Dose Expansion | Experimental | Participants in tumor-specific groups will receive 1 dosing regimen deemed to be safe in Part 1 Receives: Drug: PF-08046876 |
| Part 2 Dose Optimization | Experimental | Participants will be enrolled to 2 dosing regimens deemed to be safe in Part 1 Receives: Drug: PF-08046876 |
| Part 3 - Combination Cohort 1 | Experimental | Participants with advanced non-small cell lung cancer who have not received treatment in the metastatic/recurrent setting will receive PF-08046876 together with pembrolizumab Receives: Drug: PF-08046876; Combination Product: Pembrolizumab |
| Part 3 - Combination Cohort 2 | Experimental | Participants with advanced non-small cell lung cancer who have not received treatment in the metastatic/recurrent setting will receive PF-08046876 together with pembrolizumab and carboplatin Receives: Drug: PF-08046876; Combination Product: Pembrolizumab; Combination Product: Carboplatin |
| Part 3 - Combination Cohort 3 | Experimental | Participants with advanced urothelial cancer that has progressed after 1 to 2 prior lines of treatment in the metastatic/recurrent setting will receive PF-08046876 together with cisplatin Receives: Drug: PF-08046876; Combination Product: Cisplatin |
| Part 3 - Combination Cohort 4 | Experimental | Participants with advanced urothelial cancer that has progressed after 1 to 2 prior lines of treatment in the metastatic/recurrent setting will receive PF-08046876 together with carboplatin Receives: Drug: PF-08046876; Combination Product: Carboplatin |
| Part 3 - Combination Cohort 5 | Experimental | Participants with advanced urothelial cancer who have not received treatment in the metastatic/recurrent setting will receive PF-08046876 together with pembrolizumab Receives: Drug: PF-08046876; Combination Product: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment Emergent Adverse Events (TEAEs) estimated during the Adverse Events (AE) evaluation
AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy dose modifications.
Measured: Start of treatment up to 30 days after last dose or start of new anticancer therapy (whichever occurs first)
Part 1: Number of Participants With Dose-limiting Toxicities (DLTs): Monotherapy
Occurrence of DLTs as defined by the protocol
Measured: Baseline to end of DLT evaluation period
Part 1: Recommended Monotherapy Dose for Expansion
RDE will be based on cumulative safety, preliminary anti-tumor activity and pharmacokinetics findings
Measured: Baseline to 30 days post last study drug administration
Part 2: Recommended Monotherapy Phase 2 Dose
RP2D will be determined based on the cumulative safety, preliminary anti-tumor activity, and pharmacokinetics findings.
Measured: Baseline to 30 days post last study drug administration
Part 3: Recommended Combination Phase 2 Dose/ Recommended Combination Dose for Expansion
RP2D/RDE will be determined based on the cumulative safety, preliminary anti tumor activity and Pharmacokinetics findings.
Measured: Baseline to 30 days post last study drug administration
Secondary outcomes (10)
Objective Response Rate (ORR)
ORR defined as per Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
Measured: Baseline until the date of the first documentation of disease progression, death, or start of new anticancer therapy (approximately 2 years)
Duration of Response (DOR)
DOR as defined per RECIST 1.1.
Measured: From the date of the first objective response to the date of disease progression or death (approximately 2 years)
Progression Free Survival (PFS)
PFS as defined per RECIST 1.1.
Measured: From Baseline to date of first disease progression or death (approximately 2 Years)
Overall Survival (OS)
OS defined as the time until death due to any cause.
Measured: From baseline to up to 3 years
Pharmacokinetics (PK): Maximum Observed Serum Concentration (Cmax)
Evaluate the single and multiple dose PK of PF-08048676.
Measured: Baseline to approximately 30 days after last dose of study drug
PK: Time to Reach Maximum Observed Plasma Concentration (Tmax)
Evaluate the single and multiple dose PK of PF-08048676.
Measured: Baseline to approximately 30 days after last dose of study drug
PK: Area Under the Curve (AUC) from Time Zero to Last Quantifiable Concentration (AUClast)
Evaluate the single and multiple dose PK of PF-08048676.
Measured: Baseline to approximately 30 days after last dose of study drug
Incidence of Anti-Drug Antibody (ADA)
To evaluate the immunogenicity of PF-08046876.
Measured: Baseline to approximately 30 days after last dose of study drug
Incidence of Neutralizing Antibodies (NAb)
To evaluate the immunogenicity of PF-08046876.
Measured: Baseline to approximately 30 days after last dose of study drug
Percent change of immune cells within tumors based on multiplex immunofluorescence
This measure will assess changes in the presence or activation of immune cells in the tumor microenvironment using RNA and/or Immunohistochemistry (IHC) assays.
Measured: Baseline through 4-7 weeks after first dose of study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2025
- Study start20 Aug 2025
- Primary completion8 Jul 2028 (estimated)
- Study completion8 Jul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced/Metastatic Solid TumorsStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 540 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07090499
- Sponsor's protocol ID
- C5951001
- Other IDs
- 2025-521729-33-00, 2025
- Status last verified
- Oct 2026
- First submitted
- 21 Jul 2025
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.