A Study of SGN-CD228A in Advanced Solid Tumors

Study Overview
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Brief Summary
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This trial will study SGN-CD228A to find out whether it is an effective treatment for different kinds of cancer. It will also look at what side effects (unwanted effects) may occur. The study will have two parts. Part 1 of the study will find out how much SGN-CD228A should be given for treatment and how often. Part 2 of the study will use the dose found in Part 1 and look at how safe and effective the treatment is.

Detailed Description
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This study is designed to evaluate the safety, tolerability, PK, and antitumor activity of SGN-CD228A in select advanced solid tumors. The study will include dose escalation and dose expansion, with multiple disease-specific expansion cohorts.

Official Title
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A Phase 1 Study of SGN-CD228A in Select Advanced Solid Tumors

Conditions
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Cutaneous Melanoma, Pleural Mesothelioma, HER2 Negative Breast Neoplasms, Non-small Cell Lung Cancer, Colorectal Cancer, Pancreatic Ductal Adenocarcinoma

Intervention / Treatment
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* Drug: SGN-CD228A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Metastatic or unresectable solid malignancy that is histologically or cytologically confirmed to be one of the tumor types listed below. Participants must have relapsed, refractory, or progressive disease (PD) and should have no appropriate standard therapy available. Disease-specific escalation/expansion includes the following tumor types. Metastatic cutaneous melanoma(MCM): Metastatic or advanced cutaneous melanoma, excludes acral or mucosal varieties. Participants must have received at least 1 PD-1-targeted therapy unless contraindicated. Participants with targetable mutations should have received at least 1 therapy targeting that mutation unless contraindicated. Malignant pleural mesothelioma (MPM): Participants must have received cisplatin and pemetrexed unless contraindicated. Advanced HER2-negative breast cancer: Participants must have received 1 or more prior lines of therapy for locally advanced or metastatic disease. Prior therapies must include taxane. Hormone-receptor-positive subjects should have received CDK4/6 inhibitor therapy and have received at least 1 prior hormonally-directed therapy, unless contraindicated. Advanced non-small cell lung cancer (NSCLC): Participants must have locally advanced or metastatic EGFR wild-type NSCLC. Participants must have received platinum-based therapy and at least 1 PD-1- or PD-L1-targeted therapy as a single agent or as part of a combination unless contraindicated. Advanced colorectal cancer: Participants must have received 2 or more prior lines of therapy for locally advanced or metastatic disease, including targeted therapies as appropriate. Advanced pancreatic ductal adenocarcinoma (PDAC): Participants must have unresectable or advanced PDAC. Participants must have received 1 or more prior line of therapy for locally advanced or metastatic disease unless contraindicated. Participants should be able to provide adequate tumor tissue for biomarker analysis Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 Measurable disease per Response Evaluation Criteria for Solid Tumors version 1.1 (RECIST v1.1) Exclusion Criteria History of another malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death. Pre-existing neuropathy Grade 2 or greater Retinal or macular disease requiring treatment or ongoing active monitoring Prior receipt of SGN-CD228A or MMAE-containing agents

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-CD228A<br>SGN-CD228A monotherapy | Drug: SGN-CD228A<br>* SGN-CD228A administered into the vein (IV; intravenously)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events | Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. | Up to approximately 3.5 years | 
| Number of participants with laboratory abnormalities |  | Up to approximately 3.5 years | 
| Number of participants with dose limiting toxicities |  | Up to approximately 3.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |  | Up to approximately 3.5 years | 
| Best response per modified RECIST (mRECIST) (participants with pleural mesothelioma only) |  | Up to approximately 3.5 years | 
| Objective response rate (ORR) | A participant is determined to have an OR if they achieve a complete response (CR) or partial response (PR) after initiation of study treatment and at or prior to the end-of-treatment disease assessment. | Up to approximately 3.5 years | 
| Progression-free survival (PFS) | Defined as the time from the start of study treatment to first documentation of disease progression or death due to any cause, whichever comes first. | Up to approximately 3.5 years | 
| Overall survival (OS) | Defined as the time from the start of any study treatment to the date of death due to any cause. | Up to approximately 3.5 years | 
| Duration of objective response (DOR) | Defined as the time from start of the first documentation of objective tumor response (complete response [CR] or partial response [PR]) to the first documentation of confirm tumor progression or death due to any cause, whichever comes first. | Up to approximately 3.5 years | 
| Duration of complete response | Defined as the time from start of the first documentation of CR to the first documentation of confirmed tumor progression or to death due to any cause, whichever comes first. | Up to approximately 3.5 years | 
| Maximum concentration (Cmax) of antibody-conjugated monomethylauristatin E (acMMAE) |  | Up to approximately 3.5 years | 
| Cmax of free MMAE |  | Up to approximately 3.5 years | 
| Cmax of total antibody |  | Up to approximately 3.5 years | 
| Time to maximum concentration (Tmax) of acMMAE |  | Up to approximately 3.5 years | 
| Tmax of free MMAE |  | Up to approximately 3.5 years | 
| Tmax of total antibody |  | Up to approximately 3.5 years | 
| Area under the plasma concentration-time curve from time 0 to the last available [AUC (0-last)] of acMMAE |  | Up to approximately 3.5 years | 
| AUC(0-last) of free MMAE |  | Up to approximately 3.5 years | 
| AUC(0-last) of total antibody |  | Up to approximately 3.5 years | 
| Trough concentration (Ctrough) of acMMAE |  | Up to approximately 3.5 years | 
| Ctrough of free MMAE |  | Up to approximately 3.5 years | 
| Ctrough of total antibody |  | Up to approximately 3.5 years | 
| Incidence of anti-drug antibodies (ADA) |  | Up to approximately 3.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HER2-negative breast cancer, Seattle Genetics