PF-08046050: Given into the vein (IV; intravenous)
bevacizumab: Given into the vein (IV; intravenous)
5-Fluorouracil (5-FU): Given into the vein (IV; intravenous)
Oxaliplatin: Given into the vein (IV; intravenous)
Leucovorin (LV): Given into the vein (IV; intravenous)
Study summary
This clinical trial is studying advanced solid tumors. Solid tumors are cancers that start in a part of your body like your lungs or liver instead of your blood. Once tumors have grown bigger in one place but haven't spread, they're called locally advanced. If your cancer has spread to other parts of your body, it's called metastatic. When a cancer has gotten so big it can't easily be removed or has spread to other parts of the body, it is called unresectable. These types of cancer are harder to treat.
Participants in this study must have cancer that has come back or did not get better with treatment. Participants must have a solid tumor cancer that can't be treated with standard of care drugs.
This clinical trial uses an experimental drug called PF-08046050. PF-08046050 is a type of antibody-drug conjugate or ADC. ADCs are designed to stick to cancer cells and kill them. They may also stick to some normal cells.
This study will test the safety of PF-08046050 in participants with solid tumors that are hard to treat or have spread throughout the body.
This study has 5 different study parts. Part A and Part B of the study will find out how much PF-08046050 should be given to participants. Part C will use the information from Parts A and B to see if PF-08046050 is safe and if it works to treat certain solid tumor cancers. Part D and E of the study, together with information from Parts A and B, will find out how much PF-08046050 should be given in combination with other anti-cancer agents. Part E will use the information from Parts A, B, and D to see if PF-08046050 is safe in combination with other anti-cancer agents and if it works to treat a certain solid tumor.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
1. Tumor type:
* Participants in Part A (dose escalation) and Part B (dose optimization) must have histologically- or cytologically-confirmed metastatic or unresectable solid tumor malignancy. Must have relapsed, refractory, or progressive disease, and should have no appropriate standard therapy available.
* Participants in Part A must have one of the following tumor types: colorectal cancer (CRC); gastric carcinoma (GC) or gastroesophageal junction adenocarcinoma (GEJ); non-small cell lung cancer (NSCLC); or pancreatic ductal adenocarcinoma (PDAC).
* The tumor types to be enrolled in Part B will be identified by the sponsor from among those specified in Part A.
* Participants in Part C (dose expansion) must have one of the following histologically- or cytologically-confirmed metastatic or unresectable solid tumor malignancies.
* CRC (adenocarcinoma of the colon or rectum) and must have received no more than 2 prior chemotherapy regimens for the treatment of advanced colorectal cancer and evidence of either progressive disease or intolerance to their last regimen.
* PDAC with one or more metastatic lesions measurable by computed tomography/magnetic resonance imaging according to RECIST v1.1 criteria; and must have received no more than 1 prior chemotherapy regimen for the treatment of advanced PDAC and evidence of either progressive disease or intolerance to that regimen.
* GC or GEJ and must have received prior platinum and fluoropyrimidine-based chemotherapy.
* NSCLC and must have received platinum-based therapy. If eligible and consistent with local standard of care must have received a PD-1/PD-L1 inhibitor. In addition, participants with tumor genomic mutations/alterations for which approved targeted therapies are available per local standard of care, must have received such therapies.
* Small cell lung cancer (SCLC) and must have received platinum-based therapy for extensive-stage disease and no more than 3 prior lines of therapy. If eligible and consistent with local standard of care must have received a PD 1/PD-L1 inhibitor.
* CRC participants in Part D and Part E (bevacizumab combination therapy) must have histologically confirmed unresectable or metastatic adenocarcinoma of the colon or rectum. Received a maximum of 2 prior chemotherapy regimens for the treatment of advanced colorectal cancer and had demonstrated progressive disease or intolerance to their last regimen.
* CRC participants in Part D and Part E (5FU/LV + bevacizumab and 5FU/LV + oxaliplatin + bevacizumab combination therapy) must have histologically confirmed unresectable or metastatic adenocarcinoma of the colon or rectum. Must not have received a prior TOPO1 inhibitor (such as irinotecan or nanoliposomal irinotecan) in any setting. 1L cohorts: No prior chemotherapy for advanced disease. 2L cohorts (applicable to 5FU/LV + bevacizumab combination only): 1 prior chemotherapy regimen for the treatment of advanced disease, which must have included a fluoropyrimidine and oxaliplatin.
\> 2L PDAC participants in Part E (5FU/LV combination therapy) must have histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma. One or more metastatic lesions measurable by computed tomography/magnetic resonance imaging according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.
\> 1L PDAC participants in Part E (5FU/LV + oxaliplatin combination therapy) must have histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma that has not been previously treated in the metastatic setting. One or more metastatic lesions measurable by computed tomography/magnetic resonance imaging according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. No prior chemotherapy for PDAC with the following exception: Patients who received adjuvant/neoadjuvant chemotherapy and who had recurrence more than 12 months after completion of adjuvant/neoadjuvant chemotherapy are eligible.
2. Participants enrolled in the following study parts should have a tumor site that is accessible for biopsy(ies) and agree to biopsy(ies) and/or submission of archival tissue:
* Monotherapy dose optimization (Part B)
* Monotherapy (Part C) and combination therapy (Part E) disease-specific expansion cohorts
3. An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
4. Measurable disease per Response Evaluation in Solid Tumors (RECIST) v1.1 at baseline.
Exclusion Criteria:
1. Previous exposure to CEACAM5-targeted therapy.
2. Prior treatment with a TOPO1-targeting ADC (CPT payload), such as Enhertu (trastuzumab deruxtecan) or Trodelvy (sacituzumab govitecan).
3. History of another malignancy within 3 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy.
4. Active cerebral/meningeal disease related to the underlying malignancy. Participants with a history of cerebral/meningeal disease related to the underlying malignancy are allowed if prior central nervous system disease has been treated and the participant is clinically stable (defined as not having received steroid treatment for symptoms related to cerebral/meningeal disease for at least 2 weeks prior to enrollment and with no ongoing related AEs).
\> Criteria related to bevacizumab administration (participants in Parts D and E)
5. History of allergic reactions or hypersensitivity to bevacizumab or any of its excipients.
6. History of hypersensitivity to Chinese Hamster Ovary cell products or other recombinant human or humanized antibodies.
7. Serious non-healing wound, non-healing ulcer, or non-healing bone fracture.
8. Deep venous thromboembolic event within 4 weeks prior to enrollment
9. Known coagulopathy that increases risk of bleeding, bleeding diatheses.
10. History of any life-threatening VEGF-related adverse event
Primary outcome measure(s)
Number of participants with adverse events (AEs) — Through 30-37 days after the last study treatment, up to approximately 2 years An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention
Number of participants with laboratory abnormalities — Through 30-37 days after the last study treatment, up to approximately 2 years
Number of dose modifications due to AEs — Through end of treatment up to approximately 2 years
Number of participants with dose-limiting toxicities (DLTs) — Up to 28 days
Number of participants with DLTs by dose level — Up to 28 days
Trial sites (48)
Facility
City
Region
Status
Mayo Clinic Hospital
Phoenix
Arizona
Recruiting
Mayo Clinic
Scottsdale
Arizona
Recruiting
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
Duarte
California
Recruiting
IP Address: City of Hope Investigational Drug Services(IDS)
Duarte
California
Recruiting
University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)
Aurora
Colorado
Recruiting
University of Colorado Hospital
Aurora
Colorado
Recruiting
Florida Cancer Specialists
Orlando
Florida
Recruiting
Sarah Cannon Research Institute at Florida Cancer Specialists
Orlando
Florida
Recruiting
Sidney Kimmel Comprehensive Cancer at Johns Hopkins
Baltimore
Maryland
Recruiting
Beth Israel Deaconess Medical Center
Boston
Massachusetts
Recruiting
START Midwest
Grand Rapids
Michigan
Recruiting
Mayo Clinic Cancer Center
Rochester
Minnesota
Recruiting
Mayo Clinic
Rochester
Minnesota
Recruiting
MidAmerica Cancer Care
Kansas City
Missouri
Not Yet Recruiting
Sarah Cannon Research Institute - Pharmacy
Nashville
Tennessee
Recruiting
SCRI Oncology Partners
Nashville
Tennessee
Recruiting
The University of Texas MD Anderson Cancer Center
Houston
Texas
Recruiting
NEXT Dallas
Irving
Texas
Not Yet Recruiting
South Texas Accelerated Research Therapeutics, LLC
San Antonio
Texas
Recruiting
START Mountain Region
Salt Lake City
Utah
Recruiting
South Texas Accelerated Research Therapeutics Mountain Region
West Valley City
Utah
Recruiting
The Ottawa Hospital
Ottawa
Ontario
Recruiting
University Health Network
Toronto
Ontario
Recruiting
University Health Network, Princess Margaret Cancer Centre
Toronto
Ontario
Recruiting
McGill University Health Centre
Montreal
Quebec
Recruiting
The Sixth Affiliated Hospital of Sun Yat-sen University
Guangzhou
Guangdong
Recruiting
Shandong First Medical University Cancer Hospital
Jinan
Shandong
Not Yet Recruiting
Fudan University Shanghai Cancer Center
Shanghai
China
Not Yet Recruiting
Institut Gustave Roussy
Villejuif
Paris
Recruiting
Gustave Roussy
Villejuif
France
Recruiting
Hadassah Medical Organization
Jerusalem
Israel
Not Yet Recruiting
National Cancer Center Hospital East
Kashiwa
Chiba
Recruiting
Netherlands Cancer Institute
Amsterdam
Netherlands
Recruiting
Institut Catala d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
L'Hospitalet de Llobregat
Catalunya [cataluña]
Recruiting
Ascires Cetir
Barcelona
Spain
Recruiting
Ascires CETIR
Esplugues de Llobregat
Spain
Recruiting
Servicio de Farmacia ICO - Planta 0
L'Hospitalet de Llobregat
Spain
Recruiting
Hospital Universitario HM Sanchinarro-CIOCC-START Madrid
Madrid
Spain
Recruiting
Karolinska University Hospital
Solna
Sweden
Recruiting
ApoEx NKS
Stockholm
Sweden
Recruiting
+ 8 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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