Clinical trial NCT06131840: A Study of SGN-CEACAM5C in Adults With Advanced Solid Tumors
Official title: An Open-label Phase 1 Study to Investigate SGN-CEACAM5C in Adults With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Colorectal Neoplasms
Carcinoma, Non-Small-Cell Lung
Stomach Neoplasms
Pancreatic Ductal Adenocarcinoma
Gastroesophageal Junction Adenocarcinoma
Small Cell Lung Carcinoma
Keywords: CRC
NSCLC
PDAC
GC
GEJ
SCLC
Seattle Genetics
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2023-11-14
Enrollment: 494
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: Through 30-37 days after the last study treatment, up to approximately 2 years
measure: Number of participants with laboratory abnormalities
timeFrame: Through 30-37 days after the last study treatment, up to approximately 2 years
measure: Number of dose modifications due to AEs
timeFrame: Through end of treatment up to approximately 2 years
measure: Number of participants with dose-limiting toxicities (DLTs)
timeFrame: Up to 28 days
measure: Number of participants with DLTs by dose level
timeFrame: Up to 28 days
Secondary outcomes:
measure: Pharmacokinetic (PK) parameter - Area under the concentration-time curve (AUC)
timeFrame: Through 30-37 days after the last study treatment, up to approximately 2 years
measure: PK parameter - Maximum concentration (Cmax)
timeFrame: Through 30-37 days after the last study treatment, up to approximately 2 years
measure: PK parameter - Time to maximum concentration (Tmax)
timeFrame: Through 30-37 days after the last study treatment, up to approximately 2 years
measure: PK parameter - Trough concentration (Ctrough)
timeFrame: Through 30-37 days after the last study treatment, up to approximately 2 years
measure: Number of participants with antidrug antibodies (ADAs)
timeFrame: Through 30-37 days after the last study treatment, up to approximately 2 years
measure: Objective response rate (ORR)
timeFrame: Through end of study and up to approximately 2 years
measure: Best overall response
timeFrame: Through end of study and up to approximately 2 years
measure: Duration of response (DOR)
timeFrame: Through end of study and up to approximately 2 years
measure: Progression-free survival (PFS)
timeFrame: Through end of study and up to approximately 2 years
measure: Overall survival (OS)
timeFrame: Through end of study and up to approximately 2 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital/University of Colorado
state: Colorado
city: Orlando
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Orlando
country: United States
facility: Sarah Cannon Research Institute at Florida Cancer Specialists
state: Florida
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Nashville
country: United States
facility: Sarah Cannon Research Institute - Pharmacy
state: Tennessee
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics, LLC
state: Texas
city: West Valley City
country: United States
facility: South Texas Accelerated Research Therapeutics Mountain Region
state: Utah
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network, Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy
state: Paris
city: Villejuif
country: France
facility: Gustave Roussy
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute
city: L'Hospitalet de Llobregat
country: Spain
facility: Institut Catala d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
state: Catalunya [cataluña]
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
state: Comunidad DE Madrid
city: Madrid
country: Spain
facility: START Madrid-CIOCC_Hospital HM Sanchinarro
city: Solna
country: Sweden
facility: Karolinska University Hospital
city: Stockholm
country: Sweden
facility: ApoEx NKS
city: Edinburgh
country: United Kingdom
facility: The University of Edinburgh
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: