A Study of SGN-CD228A in Advanced Solid Tumors
Research type
Research Study
Full title
A phase 1 study of SGN-CD228A in select advanced solid tumors
IRAS ID
272168
Contact name
Anna Minchom
Contact email
Sponsor organisation
Seattle Genetics, Inc.
Eudract number
2019-001411-23
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
NA, NA
Duration of Study in the UK
3 years, 1 months, 1 days
Research summary
Research Summary
This study is being carried out to test if SGN-CD228A (investigational drug) is safe and effective for the treatment of solid tumours.
SGN-CD228A is a type of drug called an antibody drug conjugate (ADC). ADCs usually have 2 parts – antibody and drug. Antibodies are part of our immune system to help protect against infection and the drug component are designed to target specific cancer cells so that the drug part can be absorbed into the cancer cells causing cell death. We are asking patients who have one of the following types of cancers to participate in this study: breast cancer, colorectal, melanoma, mesothelioma, non-small cell lung cancer and pancreatic cancer.
This is an open label study, which means both the participants and study team know what drug is being given. All participants will be administered SGN-CD228A on Day 1 of each 21 day cycle. Participants will have various procedures throughout the study including eye examinations, blood samples, MRI/CT scans, ECGs and tumour biopsies. Participants will continue to receive study treatment and safety assessment until disease progression, toxicity, investigators decision or withdrawal of consent. After treatment discontinuation, all patients will be followed for subsequent cancer therapies and survival.
Around 240 patients may take part in the clinical trial globally at 11 study centers in US, UK, France, Italy and Spain. This study is being sponsored by Seattle Genetics, Inc.Summary of results
Data from this SGN-CD228A first-in-human study demonstrates insufficient antitumor activity in the dosing regimens tested, and the therapeutic window limits further development. Subsequently, the decision was made by the sponsor to close the study. The therapeutic window was limited by Adverse Events of ocular toxicity, peripheral neuropathy, and neutropenia. There were no deaths due to Adverse Events in the every 3 weeks (Q3W) or intermittent twice every 3 weeks (2Q3W) dosing schedules. One death occurred due to an unrelated event of respiratory failure in once weekly (Q1W) dosing schedules. The most common treatment-emergent adverse event (TEAE) was fatigue, while the most common TEAE with Grade 3 or higher severity was anemia. There were few Serious Adverse Events considered to be related to SGN-CD228A, and the most common reason for study treatment discontinuation was progressive disease. Pharmacokinetics of SGN-CD228A antibody-conjugated monomethylauristatin E (acMMAE) and released monomethylauristatin E (MMAE) were assessed using non-compartmental analysis. No accumulation over time was observed for either acMMAE or released MMAE for the Q3W dosing schedule. Exposures of acMMAE increased proportionally as dose increased, with a half-life of approximately 3 to 4 days. Exposures of released MMAE increased as dose increased but with large between-subject variability. Half-life of released MMAE was estimated approximately 5 to 6 days.
Overall, the COVID-19 pandemic did not significantly affect the ability to monitor and manage subject safety during the conduct of the study. Therefore, there was no impact on the integrity and interpretation of results for the study due to the COVID-19 pandemic.REC name
London - Chelsea Research Ethics Committee
REC reference
19/LO/1650
Date of REC Opinion
14 May 2020
REC opinion
Further Information Favourable Opinion