Clinical trial NCT04042480: A Study of SGN-CD228A in Advanced Solid Tumors
Official title: A Phase 1 Study of SGN-CD228A in Select Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Cutaneous Melanoma
Pleural Mesothelioma
HER2 Negative Breast Neoplasms
Non-small Cell Lung Cancer
Colorectal Cancer
Pancreatic Ductal Adenocarcinoma
Keywords: HER2-negative breast cancer
Seattle Genetics
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2019-08-02
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: Up to approximately 3.5 years
measure: Number of participants with laboratory abnormalities
timeFrame: Up to approximately 3.5 years
measure: Number of participants with dose limiting toxicities
timeFrame: Up to approximately 3.5 years
Secondary outcomes:
measure: Best response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
timeFrame: Up to approximately 3.5 years
measure: Best response per modified RECIST (mRECIST) (participants with pleural mesothelioma only)
timeFrame: Up to approximately 3.5 years
measure: Objective response rate (ORR)
timeFrame: Up to approximately 3.5 years
measure: Progression-free survival (PFS)
timeFrame: Up to approximately 3.5 years
measure: Overall survival (OS)
timeFrame: Up to approximately 3.5 years
measure: Duration of objective response (DOR)
timeFrame: Up to approximately 3.5 years
measure: Duration of complete response
timeFrame: Up to approximately 3.5 years
measure: Maximum concentration (Cmax) of antibody-conjugated monomethylauristatin E (acMMAE)
timeFrame: Up to approximately 3.5 years
measure: Cmax of free MMAE
timeFrame: Up to approximately 3.5 years
measure: Cmax of total antibody
timeFrame: Up to approximately 3.5 years
measure: Time to maximum concentration (Tmax) of acMMAE
timeFrame: Up to approximately 3.5 years
measure: Tmax of free MMAE
timeFrame: Up to approximately 3.5 years
measure: Tmax of total antibody
timeFrame: Up to approximately 3.5 years
measure: Area under the plasma concentration-time curve from time 0 to the last available [AUC (0-last)] of acMMAE
timeFrame: Up to approximately 3.5 years
measure: AUC(0-last) of free MMAE
timeFrame: Up to approximately 3.5 years
measure: AUC(0-last) of total antibody
timeFrame: Up to approximately 3.5 years
measure: Trough concentration (Ctrough) of acMMAE
timeFrame: Up to approximately 3.5 years
measure: Ctrough of free MMAE
timeFrame: Up to approximately 3.5 years
measure: Ctrough of total antibody
timeFrame: Up to approximately 3.5 years
measure: Incidence of anti-drug antibodies (ADA)
timeFrame: Up to approximately 3.5 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute
state: California
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center / Wake Forest University
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve University / University Hospitals Cleveland Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center (UPMC)/Hillman Cancer Center
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Cancer Center
state: South Dakota
city: Houston
country: United States
facility: MD Anderson Cancer Center / University of Texas
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics
state: Texas
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital (Surrey)
Study officials:
affiliation: Seagen Inc.
name: Anu Gupta, MD
role: STUDY_DIRECTOR
References: