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NCT06131840PHASE1Recruiting

A Study of SGN-CEACAM5C in Adults With Advanced Solid Tumors

Seagen, a wholly owned subsidiary of Pfizer

Start Date

11/20/2023

Completion Date

9/12/2030

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 Criteria

Age Range: 18 years to No maximum

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

Interventions

DRUG

PF-08046050

DRUG

bevacizumab

DRUG

5-Fluorouracil (5-FU)

DRUG

Oxaliplatin

DRUG

Leucovorin (LV)

Interested in This Trial?

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Conditions

Colorectal NeoplasmsCarcinoma, Non-Small-Cell LungStomach NeoplasmsPancreatic Ductal AdenocarcinomaGastroesophageal Junction AdenocarcinomaSmall Cell Lung Carcinoma

Locations

Mayo Clinic Hospital

Phoenix, Arizona 85054

United States

Mayo Clinic

Scottsdale, Arizona 85259

United States

City of Hope (City of Hope National Medical Center, City of Hope Medical Center)

Duarte, California 91010

United States

IP Address: City of Hope Investigational Drug Services(IDS)

Duarte, California 91010

United States

University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)

Aurora, Colorado 80045

United States

University of Colorado Hospital

Aurora, Colorado 80045

United States

Florida Cancer Specialists

Orlando, Florida 32827

United States

Sarah Cannon Research Institute at Florida Cancer Specialists

Orlando, Florida 32827

United States

Sidney Kimmel Comprehensive Cancer at Johns Hopkins

Baltimore, Maryland 21287

United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts 02215

United States

START Midwest

Grand Rapids, Michigan 49546

United States

Mayo Clinic Cancer Center

Rochester, Minnesota 55905

United States

Mayo Clinic

Rochester, Minnesota 55905

United States

MidAmerica Cancer Care

Kansas City, Missouri 64132

United States

Sarah Cannon Research Institute - Pharmacy

Nashville, Tennessee 37203

United States

SCRI Oncology Partners

Nashville, Tennessee 37203

United States

The University of Texas MD Anderson Cancer Center

Houston, Texas 77030

United States

NEXT Dallas

Irving, Texas 75039

United States

South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas 78229

United States

START Mountain Region

Salt Lake City, Utah 84119

United States

South Texas Accelerated Research Therapeutics Mountain Region

West Valley City, Utah 84119

United States

The Ottawa Hospital

Ottawa, Ontario K1H 8L6

Canada

University Health Network

Toronto, Ontario M5G 2C4

Canada

University Health Network, Princess Margaret Cancer Centre

Toronto, Ontario M5G 2M9

Canada

McGill University Health Centre

Montreal, Quebec H4A 3J1

Canada

The Sixth Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong 510655

China

Shandong First Medical University Cancer Hospital

Jinan, Shandong 250117

China

Fudan University Shanghai Cancer Center

Shanghai, 201321

China

Institut Gustave Roussy

Villejuif, Paris 94805

France

Gustave Roussy

Villejuif, 94800

France

Hadassah Medical Organization

Jerusalem, 91120

Israel

National Cancer Center Hospital East

Kashiwa, Chiba 277-8577

Japan

Netherlands Cancer Institute

Amsterdam, 1066CX

Netherlands

Institut Catala d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)

L'Hospitalet de Llobregat, Catalunya [cataluña] 08908

Spain

Ascires Cetir

Barcelona, 08029

Spain

Ascires CETIR

Esplugues de Llobregat, 08950

Spain

Servicio de Farmacia ICO - Planta 0

L'Hospitalet de Llobregat, 08908

Spain

Hospital Universitario HM Sanchinarro-CIOCC-START Madrid

Madrid, 28050

Spain

Karolinska University Hospital

Solna, 171 64

Sweden

ApoEx NKS

Stockholm, 17176

Sweden

The Harley Street Clinic (THSC)

London, Other W1G 8BJ

United Kingdom

Edinburgh Cancer Centre, Western General Hospital

Edinburgh, Scotland EH4 2XU

United Kingdom

Lothian Health Board

Edinburgh, EH3 9DN

United Kingdom

Western General Hospital

Edinburgh, EH4 2XU

United Kingdom

Sarah Cannon Research Institute UK

London, W1G 6AD

United Kingdom

Diagnostic Centre

London, W1G 7AF

United Kingdom

The Harley Street Clinic

London, W1G 7LJ

United Kingdom

Radiology

London, W1G 8PP

United Kingdom