ADC Therapeutics, an oncology drug discovery and development company, has dosed first patient in its Phase Ib clinical trial of ADCT-301 in patients with selected solid tumors that are locally advanced or metastatic.
ADCT-301 (camidanlumab tesirine) is already being evaluated in relapsed and refractory Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). In Hodgkin lymphoma, patients with a median of five prior lines of therapy and no other approved therapy options, the overall response rate was 86.5 percent, including a 43 percent complete response rate, at the dose being considered for a pivotal Phase II clinical trial that the company expects to begin this year. ADCT-301 is composed of a monoclonal antibody that binds to CD25, HuMax-TAC, licensed from Genmab A/S, conjugated to a pyrrolobenzodiazepine (PBD) dimer toxin. Once bound to a CD25-expresing cell, ADCT-301 is internalized into the cell where enzymes release the PBD-based warhead.
Jay Feingold, Chief Medical Officer and Senior Vice President of Clinical Development at ADC Therapeutics, said that ADC Therapeutics is very encouraged by the anti-tumor activity of ADCT-301 in Hodgkin lymphoma and non-Hodgkin lymphoma. He said that preclinical studies boost excited to start this clinical trial for ADCT-301 in solid tumors to see it can make an impact and improve patient outcomes in multiple difficult-to-treat solid tumor cancers.
ADC Therapeutics pointed out that, at the Society for Immunotherapy of Cancer’s (SITC) 33rd Annual Meeting, ADC Therapeutics presented preclinical data showing that an engineered version of ADCT-301 showed highly potent anti-tumor activity, both as a monotherapy and in combination with a checkpoint inhibitor, in multiple solid tumor models with infiltrating CD25-positive regulatory T cells (Tregs).
Patrick van Berkel, Senior Vice President of Research and Development at ADC Therapeutics, said: “ADCT-301 targets CD25, which is expressed on Tregs that infiltrate the local tumor environment. In preclinical models, a single dose of the CD25-targeted ADC induced strong and durable anti-tumor activity against established CD25-negative solid tumors with infiltrating Tregs both as a monotherapy and in combination with a checkpoint inhibitor. Moreover, re-challenged mice did not develop new tumors indicating the CD25-targeted ADC was able to induce tumor-specific protective immunity.”
The company added that the Phase Ib trial of ADCT-301 in patients with advanced solid tumors has both dose escalation and cohort expansion parts. The dose escalation part is designed to establish a safe and tolerated dose and dosing schedule of ADCT-301 in these patients. The identified dose and dosing schedule will be studied in the dose expansion part. Approximately 50 patients will be enrolled in the trial.