Genentech's ADC Shows Potential Against Melanoma, Says AACR

Results of a first-in-human Phase I clinical trial of Genentech’s investigational antibody drug conjugate (ADC) DEDN6525A showed promising potential against certain forms of melanoma, including cutaneous, mucosal, and ocular forms. 

Jeffrey Infante, director of the drug development program at Sarah Cannon Research Institute in Nashville, Tennessee, said, “As one of the first clinical trials to test an antibody-drug conjugate for the treatment of melanoma, we were encouraged by the initial responses. We found DEDN6525A to have a well-tolerated safety profile, and more importantly, to benefit a substantial proportion of patients. It is particularly promising to see clinical activity in patients with mucosal as well as ocular melanoma, and we hope that patients who are enrolling in the ongoing expansion phase of the trial gain similar benefit.”

Anti-EBTR (endothelin B receptor) DEDN6526A is an antibody drug conjugate composed of a monoclonal antibody directed against EBTR, link to the small molecule, cytotoxic, microtubule-disrupting agent MMAE (monomethyl auristatin). EBTR can be over-expressed in some types of melanoma. The molecule is undergoing a Phase I clinical trial for metastatic or unresectable melanoma.

Infante and colleagues conducted the dose-escalation phase of the trial in patients with metastatic or unresectable melanoma. Twelve out of 19 patients demonstrated clinical benefit, with four confirming partial responses. Other patients had stable levels of the disease for six or more months, with one patient nearing two years on the study.

“With the initial findings, we have begun to look at whether clinical activity correlates with ETBR levels on a patient’s tumor. Patients with all forms of melanoma expressing high levels of ETBR seem more likely to benefit from treatment with DEDN6526A, and we hope that further investigation of this biomarker for response to DEDN6526A will inform future development of this melanoma treatment,” Infante said.

The molecule DEDN6526A is being developed by Genentech using Seattle Genetics’ antibody drug conjugate technology.