AACR 2026 | Phase I trial of denikitug, an anti-CCR8 antibody, in advanced solid tumors

Hi, my name is Bruno Bockorny. I’m a GI oncologist practicing here in Boston. I’m from my work at Beth Israel Deaconess Medical Center and Dana-Farber Cancer Institute. So at AACR, I will present the preliminary results of the phase one first-in-human study with this anti-CCR8 antibody called denikitug in patients with advanced solid tumors. So the rationale for this study is this. Regulatory T-cells or Tregs, they are major drivers of immunosuppression within the tumor microenvironment. And their accumulation in the tumor is actually associated with worse outcomes across multiple tumor types. So we have this drug called denikitug, which is an engineered monoclonal antibody specifically designed to target these CCR8-positive intratumoral Tregs. And this antibody was designed in a way to go after the intratumoral Tregs only, and not so much the peripheral Tregs, minimizing adverse events. The phase one was a large study with two major components. One to evaluate denikitug as a monotherapy, and the other, denikitug combined with an anti-PD-1 inhibitor. For AACR, we’ll be presenting the data of the monotherapy cohorts, Part A and Part B. There was a dose escalation initially, and then a subsequent cohort where patients received doses of 10 milligrams and above, and we were also able to obtain paired biopsies to understand the immunobiological effects that denikitug was causing in the tumor microenvironment. Moving to safety, overall, the safety profile of denikitug was manageable. The main adverse events that we saw were immune-mediated skin rash and pruritus, also some diarrhea, mainly grade 1 and 2. Grade 3 adverse events were uncommon. And overall, we think this profile is very consistent with the immunomodulatory mechanism of action of Treg depletion. Now, turning to efficacy, it’s essential to point out this was a heavily pretreated population, and two-thirds of the patients had prior exposure to anti-PD-1 or anti-PD-L1 therapy. Within the 52 evaluable patients, we saw objective response rates of 8% and disease control rates of 46%. I will note that responders had a median of six prior lines of therapy, so heavily pretreated patients, and the responses were also durable. The median duration of response was 4.3 months, but ranging up to 14 months. And in terms of the immunobiological effect, we were excited to see that the drug was doing exactly what it was designed to do. After two doses of denikitug, we saw actually a major depletion of the intratumoral Tregs and a concurrent increase in expansion and infiltration by CD8-positive effector T cells.

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