ADC Therapeutics has halted the development of ADCT-502, an investigational treatment candidate for HER2-positive solid cancers, and terminated its Phase 1 trial after it failed to show sufficient patient benefit, the company recently announced.
The decision was based on data from the Phase 1 trial (NCT03125200) that showed that ADCT-502 did not meet the necessary efficacy and safety profile required for patient benefit. ADC plans to publish the findings of the trial later this year after it has evaluated all the data.
“ADC Therapeutic’s strategy is to progress a deep pipeline of ADCs into Phase 1 in order to assess their clinical and market potential based on actual human data, and only to progress into later stage development those ADCs that demonstrate the potential to be best in class in areas of high unmet medical need,” Chris Martin, CEO of ADCT, said in a press release.
ADCT-502 is antibody-drug conjugate composed of an anti-HER2 antibody bound to a toxic compound. After binding to an HER2-positive cell, it releases its payload, leading to the cell’s death without harming healthy tissues.
The antibody used in ADCT-502, called trastuzumab, is already approved for certain HER2-positive cancers, including metastatic breast cancer. This antibody is marketed by Roche under the brand name Herceptin. But ADC is using trastuzumab bound to the toxic compound tesirine.
In mouse models of HER-positive breast, gastric, and esophageal cancers, a single injection of ADCT-502 significantly delayed tumor growth. And its anti-cancer activity was markedly better than Kadcyla (ado-trastuzumab emtansine), an antibody-drug conjugate already approved for HER2-positive metastatic breast cancer.
Based on this data, a Phase 1 trial was designed to test ADCT-502 in HER2-positive cancers. While the trial was planned to have two parts, the expected risk/benefit ratio had not been achieved by the end of part one.
The study enrolled roughly 20 patients with solid cancers, including breast cancer, non-small cell lung cancer, gastroesophageal, and bladder cancer.
In the first part, it tested the safety and tolerability of ascending ADCT-502 doses. But results showed that anti-cancer responses were only seen at higher doses, which were not well-tolerated by patients. As a result, the trial failed to achieve its primary objective and was suspended.
“We are very pleased with the efficacy and tolerability achieved with our lead hematological PBD-based ADC programs, but regrettably this has not been the case with our HER2 targeted ADC,” said Jay Feingold, MD, PhD, ADC’s chief medical officer and senior vice president of clinical development. “During dose escalation in this trial we did not achieve the necessary efficacy at tolerated doses required for patient benefit. This was possibly due to the extensive expression of HER2 in pulmonary tissue.”
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