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

Study Overview
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Brief Summary
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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. Patients in this study must have cancer that has come back or did not get better with treatment. Patients must have a solid tumor cancer that can't be treated with standard of care drugs. This clinical trial uses an experimental drug called SGN-CEACAM5C. SGN-CEACAM5C 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 SGN-CEACAM5C in participants with solid tumors that are hard to treat or have spread throughout the body. This study will have 3 parts. Part A and Part B of the study will find out how much SGN-CEACAM5C should be given to participants. Part C will use the information from Parts A and B to see if SGN-CEACAM5C is safe and if it works to treat solid tumor cancers.

Official Title
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An Open-label Phase 1 Study to Investigate SGN-CEACAM5C in Adults With Advanced Solid Tumors

Conditions
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Colorectal Neoplasms, Carcinoma, Non-Small-Cell Lung, Stomach Neoplasms, Pancreatic Ductal Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Small Cell Lung Carcinoma

Intervention / Treatment
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* Drug: SGN-CEACAM5C


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Tumor type: Participants in Part A (dose escalation) must have histologically- or cytologically-confirmed metastatic or unresectable solid tumor malignancy. Participants must have relapsed, refractory, or progressive disease, and should have no appropriate standard therapy available at the time of enrollment in the judgement of the investigator. Participants must have one of the following tumor types: Colorectal cancer (CRC) Gastric carcinoma (GC) (including signet-ring cell histology) and gastroesophageal junction adenocarcinoma (GEJ) Non-small cell lung cancer (NSCLC), squamous or non-squamous histology Pancreatic ductal adenocarcinoma (PDAC) For Part B (dose optimization) and Part C (dose expansion): Participants must have histologically- or cytologically-confirmed metastatic or unresectable solid tumor malignancy. The tumor types to be enrolled in dose optimization will be identified by the sponsor from among those specified in dose escalation. CRC Prior therapy: Participants must have received prior treatment (in 1 or more lines of therapy) containing fluoropyrimidine, oxaliplatin, and irinotecan. PDAC Prior therapy: Participants 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/GEJ Prior therapy: Participants must have received prior platinum and fluoropyrimidine-based chemotherapy. NSCLC - non-squamous/squamous Prior therapy: Participants must have received platinum-based therapy. If eligible and consistent with local standard of care must have received a PD-1/PD-L1 inhibitor. Small cell lung cancer (SCLC) Prior therapy: Participants must have received platinum-based therapy for extensive-stage disease and no more than 3 prior lines of therapy 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 Dose optimization 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 an antibody-drug conjugate (ADC) with a camptothecin payload 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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SGN-CEACAM5C<br>SGN-CEACAM5C monotherapy | Drug: SGN-CEACAM5C<br>* Given into the vein (IV; intravenous)<br>* Other names: SAR445953;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events (AEs) | 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 | Through 30-37 days after the last study 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 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) parameter - Area under the concentration-time curve (AUC) | PK endpoint | Through 30-37 days after the last study treatment, up to approximately 2 years | 
| PK parameter - Maximum concentration (Cmax) | PK endpoint | Through 30-37 days after the last study treatment, up to approximately 2 years | 
| PK parameter - Time to maximum concentration (Tmax) | PK endpoint | Through 30-37 days after the last study treatment, up to approximately 2 years | 
| PK parameter - Trough concentration (Ctrough) | PK endpoint | Through 30-37 days after the last study treatment, up to approximately 2 years | 
| 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) | 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. | Through end of study and up to approximately 2 years | 
| Best response | The best 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. | Through end of study and up to approximately 2 years | 
| Duration of response (DOR) | 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 | Through end of study and up to approximately 2 years | 
| Progression-free survival (PFS) | 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 | Through end of study and up to approximately 2 years | 
| Overall survival (OS) | OS is defined as the time from start of SGN-CEACAM5C to date of death due to any cause | Through end of study and up to approximately 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CRC, NSCLC, PDAC, GC, GEJ, SCLC, Seattle Genetics