Cambridge Healthtech Institute’s Mary Ruberry spoke with Dr. David M. Goldenberg of Garden State Cancer Center and Immunomedics, Inc. Dr. Goldenberg will be presenting on “Therapy of Advanced Solid Cancers with Sacituzumab Govitecan (IMMU-132), a Novel ADC Targeting Trop-2” at the 3rd Annual “Antibody-Drug Conjugates” conference taking place January 19-20, 2016, as part of PepTalk in San Diego, CA.
Q1: How does your work target cancer?
We have developed a second-generation antibody-drug conjugate (ADC) that targets solid cancers expressing Trop-2, which is a novel marker for many epithelial cancers and is considered by many as prognostic for a number of cancers.
Q2: Can you explain how IMMU-132 functions?
The humanized anti-Trop-2 IgG is conjugated site-selectively with a high ratio of SN-38, a topoisomerase I inhibitor that is the active metabolite of irinotecan. The ADC has a proprietary linker that permits release of the drug at the tumor or after internalization, and does not convert readily to the glucuronidated form, thus not showing the severe diarrhea experienced in patients with irinotecan. Preclinical studies have confirmed a high, selective uptake in various solid tumor xenografts, as compared to irinotecan or an irrelevant SN-38 conjugate.
Q3: What are the results you’re seeing?
Based on studying over 250 patients with advanced, metastatic cancers in patients who have failed multiple prior therapies, we have confirmed objective and durable anti-tumor activity as measured by CT (RECIST 1.1), especially at the dosing determined for future Phase 3 trials, while manageable neutropenia has been the major toxicity. In the most advanced subgroup, patients with metastatic triple-negative breast cancer (mTNBC), an objective response rate (PR+CR) of about 30% has been achieved, with a progression-free survival (PFS) of about 7.0 months measured so far. Equally good responses have been obtained in patients with non-small cell and small-cell lung cancers, as well as patients with urothelial cancers, but in smaller patient numbers.
Q4: How did your group develop your proprietary linker?
We investigated a number of constructs, and determined empirically that the one that is most or least stable is not as effective as one of a moderate stability. Further, in contrast to the current dogma of using a supertoxic drug at a low drug:antibody ratio, we have shown that a moderately-toxic drug conjugated at a high drug:antibody ratio can permit repeated, high doses to be given, producing a higher-therapeutic index in patients than experienced by other ADCs.
Q5: Can you address your goals for the future, and where you see ADCs headed?
We are advancing our trials to Phase 3 studies for several cancer types.
David M. Goldenberg, M.D., Professor and President, Garden State Cancer Center and Chairman, Chief Scientific & Chief Patent Officer, Immunomedics, Inc.
David M. Goldenberg, M.D., Sc.D., founded Immunomedics, Inc., a publicly-traded biopharmaceutical company, in July 1982, and has served continuously as Chairman of the Board of Directors. He also serves as Chairman of the Board of Directors of IBC Pharmaceuticals, Inc., a subsidiary of Immunomedics. Dr. Goldenberg held professional appointments at the University of Pittsburgh, Temple University, University of Kentucky, University of Medicine and Dentistry of New Jersey, and New York Medical College. He has written or co-authored approximately 1,800 journal articles, book chapters, and abstracts on cancer research, detection and treatment and has been a leader in the area of monoclonal antibodies.
To learn more about Dr. Goldenberg’s presentation at the 3rd Annual “Antibody-Drug Conjugates” conference, visit