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

Phase 1

Recruiting

• Conditions: Carcinoma, Non-Small-Cell Lung; Stomach Neoplasms; Small Cell Lung Carcinoma; Gastroesophageal Junction Adenocarcinoma; Colorectal Neoplasms; Pancreatic Ductal Adenocarcinoma
• Interventions: Drug: PF-08046050; Drug: bevacizumab

• Registration Number: NCT06131840
• Lead Sponsor: Seagen, a wholly owned subsidiary of Pfizer

Brief 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 of the study, together with information from Parts A and B, will find out how much PF-08046050 should be given to participants in combination with bevacizumab. Part E will use the information from Parts A, B, and D to see if PF-08046050 is safe in combination with bevacizumab and if it works to treat a certain solid tumor.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-11-09
• Study First Submitted QC: 2023-11-09
• Study First Posted: 2023-11-14
• Study Start: 2023-11-20
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-12
• Last Update Posted: 2025-05-13
• Primary Completion: 2029-08-18
• Study Completion: 2030-02-14

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 494

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 and must have received prior treatment (in 1 or more lines of therapy) containing fluoropyrimidine, oxaliplatin, and irinotecan.
     • PDAC and must have received 1 prior line of therapy and received no more than 3 prior lines of therapy in the advanced or metastatic setting.
     • 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.

   • Participants in Part D (bevacizumab combination therapy dose escalation) must have histologically confirmed unresectable or metastatic adenocarcinoma of the colon or rectum. Must have demonstrated progressive disease or intolerance to their last treatment regimen. Prior treatment regimens must have included fluoropyrimidine, irinotecan, oxaliplatin, an anti-VEGF monoclonal antibody and/or an anti-EGFR monoclonal antibody for RAS wildtype participants.

   • Participants in Part E (bevacizumab combination therapy dose expansion) must have histologically confirmed unresectable or metastatic adenocarcinoma of the colon or rectum. Must have received a maximum of 2 prior chemotherapy regimens for the treatment of advanced CRC and had demonstrated progressive disease or intolerance to their last regimen. Prior treatment regimens must have included a fluoropyrimidine, irinotecan, oxaliplatin, an anti-VEGF monoclonal antibody and/or an anti-EGFR monoclonal antibody for RAS wildtype participants.

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 bevacizumab 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 an antibody-drug conjugate (ADC) with a camptothecin payload

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
PF-08046050	PF-08046050	PF-08046050 monotherapy
PF-08046050 +bevacizumab	PF-08046050	PF-08046050 combination with bevacizumab
PF-08046050 +bevacizumab	bevacizumab	PF-08046050 combination with bevacizumab

Primary Outcome Measures

Name	Time	Method
Number of participants with DLTs by dose level	Up to 28 days
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 dose modifications due to AEs	Through end of treatment up to approximately 2 years
Number of participants with laboratory abnormalities	Through 30-37 days after the last study treatment, up to approximately 2 years
Number of participants with dose-limiting toxicities (DLTs)	Up to 28 days

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic (PK) parameter - Area under the concentration-time curve (AUC)	Through 30-37 days after the last study treatment, up to approximately 2 years	PK endpoint
Best overall response	Through end of study and up to approximately 2 years	The best overall response for a participant will be determined by the order of confirmed CR, confirmed PR, stable disease (SD), progressive disease (PD), not evaluable (NE) or not applicable (NA) per RECIST v1.1.
Overall survival (OS)	Through end of study and up to approximately 2 years	OS is defined as the time from start of SGN-CEACAM5C to date of death due to any cause
PK parameter - Maximum concentration (Cmax)	Through 30-37 days after the last study treatment, up to approximately 2 years	PK endpoint
Duration of response (DOR)	Through end of study and up to approximately 2 years	DOR is defined as the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of tumor progression per RECIST v1.1 or to death due to any cause
PK parameter - Time to maximum concentration (Tmax)	Through 30-37 days after the last study treatment, up to approximately 2 years	PK endpoint
Number of participants with antidrug antibodies (ADAs)	Through 30-37 days after the last study treatment, up to approximately 2 years
Objective response rate (ORR)	Through end of study and up to approximately 2 years	The objective response rate (ORR) is defined as the percentage of participants with complete response (CR) or partial response (PR) which is subsequently confirmed as assessed according to Response Evaluation in Solid Tumors (RECIST) v1.1.
Progression-free survival (PFS)	Through end of study and up to approximately 2 years	PFS is defined as the time from start of SGN-CEACAM5C to first documentation of disease progression (based on radiographic assessments per RECIST v1.1) or death due to any cause, whichever comes first
PK parameter - Trough concentration (Ctrough)	Through 30-37 days after the last study treatment, up to approximately 2 years	PK endpoint

Trial Locations

Locations (38)

Mayo Clinic Hospital; 🇺🇸 Phoenix, Arizona, United States

Sarah Cannon Research Institute at Florida Cancer Specialists; 🇺🇸 Orlando, Florida, United States

SCRI Oncology Partners; 🇺🇸 Nashville, Tennessee, United States

South Texas Oncology and Hematology; 🇺🇸 San Antonio, Texas, United States

University of Ottawa/Ottawa General Hospital; 🇨🇦 Ottawa, Ontario, Canada

Institut Gustave Roussy; 🇫🇷 Villejuif Cedex, Paris, France

Hospital Universitario HM Sanchinarro; 🇪🇸 Madrid, Comunidad DE Madrid, Spain

ApoEx NKS; 🇸🇪 Stockholm, Sweden

City of Hope; 🇺🇸 Duarte, California, United States

South Texas Accelerated Research Therapeutics; 🇺🇸 San Antonio, Texas, United States

University of Ottawa / Ottawa General Hospital; 🇨🇦 Ottawa, Ontario, Canada

Institut Catala d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet); 🇪🇸 L'Hospitalet de Llobregat, Catalunya [cataluña], Spain

Mayo Clinic; 🇺🇸 Scottsdale, Arizona, United States

Sidney Kimmel Comprehensive Cancer at Johns Hopkins; 🇺🇸 Baltimore, Maryland, United States

South Texas Accelerated Research Therapeutics, LLC; 🇺🇸 San Antonio, Texas, United States

Johns Hopkins Medical Center; 🇺🇸 Baltimore, Maryland, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

South Texas Accelerated Research Therapeutics Midwest; 🇺🇸 Grand Rapids, Michigan, United States

Sarah Cannon Research Institute UK; 🇬🇧 London, United Kingdom

University of Colorado Anschutz Cancer Pavilion; 🇺🇸 Aurora, Colorado, United States

The University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

McGill University Health Centre; 🇨🇦 Montreal, Quebec, Canada

Gustave Roussy; 🇫🇷 Villejuif, France

Florida Cancer Specialists - Lake Nona; 🇺🇸 Orlando, Florida, United States

MD Anderson Cancer Center / University of Texas; 🇺🇸 Houston, Texas, United States

Netherlands Cancer Institute; 🇳🇱 Amsterdam, Netherlands

Karolinska University Hospital; 🇸🇪 Solna, Sweden

The University of Edinburgh; 🇬🇧 Edinburgh, United Kingdom

University of Colorado Hospital/University of Colorado; 🇺🇸 Aurora, Colorado, United States

Florida Cancer Specialists; 🇺🇸 Orlando, Florida, United States

Sarah Cannon Research Institute - Pharmacy; 🇺🇸 Nashville, Tennessee, United States

South Texas Accelerated Research Therapeutics Mountain Region; 🇺🇸 West Valley City, Utah, United States

Royal Victoria Hospital, McGill University Health Centre; 🇨🇦 Montreal, Quebec, Canada

START Madrid-CIOCC_Hospital HM Sanchinarro; 🇪🇸 Madrid, Spain

START Midwest; 🇺🇸 Grand Rapids, Michigan, United States

Mayo Clinic Cancer Center; 🇺🇸 Rochester, Minnesota, United States

Tennessee Oncology-Nashville/Sarah Cannon Research Institute; 🇺🇸 Nashville, Tennessee, United States

University Health Network, Princess Margaret Hospital; 🇨🇦 Toronto, Ontario, Canada