The study (NCT03685344) is for adults with advanced diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), or follicular lymphoma (FL) who have relapsed or refractory disease and have failed or been intolerant to standard treatment.
Patient enrollment, for a planned total of 75 participants, is ongoing at sites in the U.S. More information on contacts and locations can be found here.
The open-label trial will include a dose-escalation part, followed by a dose-expansion stage. This second part will include up to three groups — one for each lymphoma type — to collect additional safety and early anti-tumor activity data at the maximum tolerated dose.
ADCT-402, by ADC Therapeutics, belongs to a class to compounds known as antibody-drug conjugates, consisting of a cancer-targeting antibody bound to a toxic molecule. The investigational therapy binds to CD19, a protein found on the surface of many types of blood cancer cells, and carries a toxin called pyrrolobenzodiazepine, which is able to kill cancer cells.
In turn, AstraZeneca’s Imfinzi binds to a protein found on cancer cells called PD-L1, preventing its interaction with the PD-1 and CD80 proteins on immune T-cells. Through this mechanism, Imfinzi, an immune checkpoint inhibitor, blocks a strategy used by cancer cells to evade immune attack, boosting anti-tumor responses.
Early results of a Phase 1 study (NCT02669017) in 183 patients with B-cell non-Hodgkin’s lymphoma — who had relapsed or failed to respond to previous therapies — revealed that ADCT-402 induced responses in most cases.
Updated data presented at the 2018 American Society of Hematology (ASH) Annual Meeting showed that 43.3% of patients receiving an ADCT-402 dose of 120 µg/kg or higher responded to treatment, including 23.6% complete responses.
The responses were particularly high among those with MCL and FL — 46.7% and 78.6%, respectively, saw a reduction in tumor volume. Both subgroups had not reached a median duration of response, which means that the patients were still responding to treatment.
In 139 patients with DLBCL, 15 with MCL and 14 with FL, treatment with ADCT-402 demonstrated manageable toxicity.
“We are now excited to explore the possible impact of ADCT-402 plus durvalumab (Imfinzi) in patient populations that would greatly benefit from new treatment options,” Jay Feingold, MD, PhD, ADC’s chief medical officer and senior vice president of clinical development, said in a press release.
Craig Moskowitz, MD, an investigator in the trial and physician in chief for the Cancer Service Line of the University of Miami’s Sylvester Comprehensive Cancer Center, said: “I look forward to evaluating this combination therapy of ADCT-402 and a PD-L1 blocker” in patients “who have failed or are intolerant to established therapies, or who don’t have other available treatment options.”
ADCT-402 is also being tested in a pivotal Phase 2 trial in patients with relapsed or refractory DLBCL (NCT03589469). This study — still recruiting participants — is expected to support the submission of a biologics license application (BLA) to the U.S. Food and Drug Administration for this indication.