ADC Therapeutics has pulled the plug on its Phase I drug candidate that targets solid tumors with HER2 expression.
Switzerland-based ADC Therapeutics has pulled the plug on its Phase I drug candidate that targets solid tumors with HER2 expression.
The privately-held company said it shuttered the program for its antibody drug conjugate (ADC) ADCT-502 due to toxicity concerns. ADCT-502 is composed of the humanized monoclonal antibody trastuzumab, which is directed against the human epidermal growth factor receptor 2 (HER2). The antibody is site-specifically conjugated to the PBD-based linker-drug tesirine.
The first patients were dosed in a Phase I trial last year for patients with advanced solid tumors with HER2 expression, which is found in a wide variety of solid tumors, including breast, gastric, esophageal, bladder and lung cancer.
In a statement issued this morning Jay Feingold, chief medical officer for ADC Therapeutics, Feingold said the company has been pleased with its lead hematological PBD-based ADC programs but said that hasn’t been the case with the ADCT-502 program. Feingold said the PBDs, which are pyrrolobenzodiazepine dimers, are potent but do have some noted side effects such as fluid retention and pulmonary edema. Most of the time those side effects can be managed by careful dosing regimens that are “efficacious with manageable toxicities.” However, during the Phase I trial for ADCT-502, Feingold said the company was unable to achieve the necessary efficacy at tolerated doses required for patient benefit.
“This was possibly due to the extensive expression of HER2 in pulmonary tissue,” Feingold said.
The company said it is collecting and evaluating the data from the Phase I study and intends to present the information in a published report later this year.
Despite the setback with ADCT-502, Feingold said the company has two solid tumor ADCs progressing into the clinic over the next nine months. He said both candidates “incorporate site-specific conjugation technology.” During preclinical programs, Feingold said data showed the two candidates have the potential to “substantially improve tolerability and efficacy in difficult to treat solid tumors.” Preclinical data on these programs were presented at the recent American Association of Cancer Research conference.
ADC Therapeutics Chief Executive Officer Chris Martin said the company’s strategy is to develop a “deep pipeline” of Phase I ADC candidates. Martin said the company would only drive those candidates that have the potential to be best in class in areas of high unmet medical need into later-stage development. Martin indicated that the company intends to advance three candidates into clinical trials later this year, but did not specify which ones. On the company’s website, however, the three candidates appear to be ADCT-601, for the treatment of metastatic solid tumors, ADCT-701 for solid tumors in the liver and ADCT-602, for Non-Hodgkin’s Lymphoma.
Other Phase I candidates the company has in its pipeline include ADCT-301 and ADCT-402, both of which are being developed to target subtypes of lymphoma and leukemia. Both of those appear to be ready to move into mid-stage trials.
The company does have sufficient funds to drive its programs further in the clinic. Last fall the company secured $200 million in financing from a number of companies, including AstraZeneca.
