A Study of SGN-CD228A in Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT04042480
• Recruitment Status: Terminated
• First Posted: August 2, 2019
• Last Update Posted: March 23, 2023
• Sponsor: Seagen Inc.
• Information provided by (Responsible Party): Seagen Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cutaneous Melanoma; Pleural Mesothelioma; HER2 Negative Breast Neoplasms; Non-small Cell Lung Cancer; Colorectal Cancer; Pancreatic Ductal Adenocarcinoma	Drug: SGN-CD228A	Phase 1

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 88 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study of SGN-CD228A in Select Advanced Solid Tumors
• Actual Study Start Date: September 3, 2019
• Actual Primary Completion Date: March 9, 2023
• Actual Study Completion Date: March 9, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: SGN-CD228A; SGN-CD228A monotherapy	Drug: SGN-CD228A; SGN-CD228A administered into the vein (IV; intravenously)

Outcome Measures

Primary Outcome Measures :

1. Number of participants with adverse events [ Time Frame: Up to approximately 3.5 years ]
   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.
2. Number of participants with laboratory abnormalities [ Time Frame: Up to approximately 3.5 years ]
3. Number of participants with dose limiting toxicities [ Time Frame: Up to approximately 3.5 years ]

Secondary Outcome Measures :

1. Best response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: Up to approximately 3.5 years ]
2. Best response per modified RECIST (mRECIST) (participants with pleural mesothelioma only) [ Time Frame: Up to approximately 3.5 years ]
3. Objective response rate (ORR) [ Time Frame: Up to approximately 3.5 years ]
   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.
4. Progression-free survival (PFS) [ Time Frame: Up to approximately 3.5 years ]
   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.
5. Overall survival (OS) [ Time Frame: Up to approximately 3.5 years ]
   Defined as the time from the start of any study treatment to the date of death due to any cause.
6. Duration of objective response (DOR) [ Time Frame: Up to approximately 3.5 years ]
   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.
7. Duration of complete response [ Time Frame: Up to approximately 3.5 years ]
   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.
8. Maximum concentration (Cmax) of antibody-conjugated monomethylauristatin E (acMMAE) [ Time Frame: Up to approximately 3.5 years ]
9. Cmax of free MMAE [ Time Frame: Up to approximately 3.5 years ]
10. Cmax of total antibody [ Time Frame: Up to approximately 3.5 years ]
11. Time to maximum concentration (Tmax) of acMMAE [ Time Frame: Up to approximately 3.5 years ]
12. Tmax of free MMAE [ Time Frame: Up to approximately 3.5 years ]
13. Tmax of total antibody [ Time Frame: Up to approximately 3.5 years ]
14. Area under the plasma concentration-time curve from time 0 to the last available [AUC (0-last)] of acMMAE [ Time Frame: Up to approximately 3.5 years ]
15. AUC(0-last) of free MMAE [ Time Frame: Up to approximately 3.5 years ]
16. AUC(0-last) of total antibody [ Time Frame: Up to approximately 3.5 years ]
17. Trough concentration (Ctrough) of acMMAE [ Time Frame: Up to approximately 3.5 years ]
18. Ctrough of free MMAE [ Time Frame: Up to approximately 3.5 years ]
19. Ctrough of total antibody [ Time Frame: Up to approximately 3.5 years ]
20. Incidence of anti-drug antibodies (ADA) [ Time Frame: Up to approximately 3.5 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35249

United States, California

The Angeles Clinic and Research Institute

Los Angeles, California, United States, 90025

United States, Illinois

University of Chicago Medical Center

Chicago, Illinois, United States, 60637

United States, North Carolina

Wake Forest Baptist Medical Center / Wake Forest University

Winston-Salem, North Carolina, United States, 27157

United States, Ohio

Case Western Reserve University / University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States, 44106

United States, Oregon

Oregon Health and Science University

Portland, Oregon, United States, 97239

United States, Pennsylvania

University of Pittsburgh Medical Center (UPMC)/Hillman Cancer Center

Pittsburgh, Pennsylvania, United States, 15232

United States, South Dakota

Sanford Cancer Center

Sioux Falls, South Dakota, United States, 57104

United States, Texas

MD Anderson Cancer Center / University of Texas

Houston, Texas, United States, 77030

South Texas Accelerated Research Therapeutics

San Antonio, Texas, United States, 78229

France

Institut Gustave Roussy

Villejuif Cedex, France, 94805

Italy

Istituto Europeo di Oncologia

Milano, Italy, 20141

Spain

Hospital Universitario Vall d'Hebron

Barcelona, Spain, 08035

United Kingdom

The Royal Marsden Hospital (Surrey)

Sutton, United Kingdom, SM2 5PT

Sponsors and Collaborators

Seagen Inc.

Investigators

• Study Director: Anu Gupta, MD; Seagen Inc.

More Information

• Responsible Party: Seagen Inc.
• ClinicalTrials.gov Identifier: NCT04042480
• Other Study ID Numbers: SGN228-001
• First Posted: August 2, 2019
• Last Update Posted: March 23, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Seagen Inc.:

HER2-negative breast cancer; Seattle Genetics

Additional relevant MeSH terms:

Mesothelioma; Breast Neoplasms; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenoma; Neoplasms, Mesothelial; Breast Diseases; Skin Diseases