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

Official title

An Open-label Phase 1 Study to Investigate PF-08046050 (SGN-CEACAM5C) in Adults With Advanced Solid Tumors

Overview

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.

Interventions

• Drug PF-08046050
  Given into the vein (IV; intravenous)
• Drug bevacizumab
  Given into the vein (IV; intravenous)
• Drug 5-Fluorouracil (5-FU)
  Given into the vein (IV; intravenous)
• Drug Oxaliplatin
  Given into the vein (IV; intravenous)
• Drug Leucovorin (LV)
  Given into the vein (IV; intravenous)

Primary outcome measures

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

Secondary outcome measures (10)

• Pharmacokinetic (PK) parameter - Area under the concentration-time curve (AUC) [Time frame: Through 30-37 days after the last study treatment, up to approximately 2 years]
• PK parameter - Maximum concentration (Cmax) [Time frame: Through 30-37 days after the last study treatment, up to approximately 2 years]
• PK parameter - Time to maximum concentration (Tmax) [Time frame: Through 30-37 days after the last study treatment, up to approximately 2 years]
• PK parameter - Trough concentration (Ctrough) [Time frame: Through 30-37 days after the last study treatment, up to approximately 2 years]
• Number of participants with antidrug antibodies (ADAs) [Time frame: Through 30-37 days after the last study treatment, up to approximately 2 years]
• Objective response rate (ORR) [Time frame: Through end of study and up to approximately 2 years]
• Best overall response [Time frame: Through end of study and up to approximately 2 years]
• Duration of response (DOR) [Time frame: Through end of study and up to approximately 2 years]
• Progression-free survival (PFS) [Time frame: Through end of study and up to approximately 2 years]
• Overall survival (OS) [Time frame: Through end of study and up to approximately 2 years]

Eligibility criteria

Inclusion criteria

• 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.

• 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
• An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
• Measurable disease per Response Evaluation in Solid Tumors (RECIST) v1.1 at baseline.

Exclusion criteria

• Previous exposure to CEACAM5-targeted therapy.
• Prior treatment with a TOPO1-targeting ADC (CPT payload), such as Enhertu (trastuzumab deruxtecan) or Trodelvy (sacituzumab govitecan).
• 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.
• 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)

• History of allergic reactions or hypersensitivity to bevacizumab or any of its excipients.
• History of hypersensitivity to Chinese Hamster Ovary cell products or other recombinant human or humanized antibodies.
• Serious non-healing wound, non-healing ulcer, or non-healing bone fracture.
• Deep venous thromboembolic event within 4 weeks prior to enrollment
• Known coagulopathy that increases risk of bleeding, bleeding diatheses.
• History of any life-threatening VEGF-related adverse event

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 21 centers

• Mayo Clinic Hospital — Phoenix
• Mayo Clinic — Scottsdale
• City of Hope (City of Hope National Medical Center, City of Hope Medical Center) — Duarte
• IP Address: City of Hope Investigational Drug Services(IDS) — Duarte
• University of Colorado Hospital - Anschutz Cancer Pavilion (ACP) — Aurora
• University of Colorado Hospital — Aurora
• Florida Cancer Specialists — Orlando
• Sarah Cannon Research Institute at Florida Cancer Specialists — Orlando
• … and 13 more centers

United Kingdom · 8 centers

• The Harley Street Clinic (THSC) — London
• Edinburgh Cancer Centre, Western General Hospital — Edinburgh
• Lothian Health Board — Edinburgh
• Western General Hospital — Edinburgh
• Sarah Cannon Research Institute UK — London
• Diagnostic Centre — London
• The Harley Street Clinic — London
• Radiology — London

Spain · 5 centers

• Institut Catala d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet) — L'Hospitalet de Llobregat
• Ascires Cetir — Barcelona
• Ascires CETIR — Esplugues de Llobregat
• Servicio de Farmacia ICO - Planta 0 — L'Hospitalet de Llobregat
• Hospital Universitario HM Sanchinarro-CIOCC-START Madrid — Madrid

Canada · 4 centers

• The Ottawa Hospital — Ottawa
• University Health Network — Toronto
• University Health Network, Princess Margaret Cancer Centre — Toronto
• McGill University Health Centre — Montreal

China · 3 centers

• The Sixth Affiliated Hospital of Sun Yat-sen University — Guangzhou
• Shandong First Medical University Cancer Hospital — Jinan
• Fudan University Shanghai Cancer Center — Shanghai

France · 2 centers

• Institut Gustave Roussy — Villejuif
• Gustave Roussy — Villejuif

Sweden · 2 centers

• Karolinska University Hospital — Solna
• ApoEx NKS — Stockholm

Israel · 1 center

• Hadassah Medical Organization — Jerusalem

Japan · 1 center

• National Cancer Center Hospital East — Kashiwa

Netherlands · 1 center

• Netherlands Cancer Institute — Amsterdam

Identifiers

NCT: NCT06131840 · SGNCEA5C-001 · C5831001 · 2023-505858-18-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗